METABOLIC PATTERNS OF A GROUP OF OVERWEIGHT, UNDERWEIGHT AND AVERAGE WEIGHT WOMEN By Betty Eileen Hawthorne AN ABSTRACT Submitted to the School of Graduate Studies of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Foods and Nutrition 195^ Approved^ ______ Betty Eileen Hawthorne METABOLIC PATTERNS OF A GROUP OF OVERWEIGHT, UNDERWEIGHT AND AVERAGE WEIGHT WOMEN Possible metabolic differences in the utilization of fat and carbo­ hydrate by women of average, above and less than average body weight were investigated through simultaneous respiration studies and analyses of various blood and urinary constituents at fasting and at intervals for five hours following two test meals. Twenty-one apparently healthy women, seven overweight, seven underweight and seven average weight, served as subjects; their weights ranged from 466 to -21 percent of desirable weight. Fat, carbohydrate and protein, respectively, contributed ?0 , 25 and 5 percent of the calories in the high fat test meal and 0 .5 , 9^.5 a^d 5 percent of the calories in the high carbohydrate test meal. The mean basal energy expenditure of the overweight subjects was significantly higher and of the underweight subjects was significantly lower than that of the average weight subjects. Fasting blood glucose concen­ trations were significantly higher among the overweight than among the other subjects. Fasting blood pyruvic acid concentrations were significantly higher among the overweight than among the underweight subjects. There were no significant group differences in fasting mean non-protein respiratory quotients, hourly urinary nitrogen excretions, in concentrations of venous serum alkaline phosphatase or of the various serum lipid constituents; total lipids, total cholesterol, lipoproteins or chylomicrons. Following both test meals, hourly calorie expenditures of the over­ weight subjects were consistently higher than those of the other subjects. Betty Eileen Hawthorne Cumulative energy increments were significantly higher among the under­ weight subjects than among the other groups following the high fat test meal. There were no significant differences in mean non-protein respiratory ouotients following either test meal. Following the high fat test meal blood glucose concentrations increased more slowly among the overweight than among the other subjects, were elevated for a longer period and then de­ creased significantly below fasting values at the fourth and fifth hours. The overweight subjects had the highest one-half hour blood glucose concen­ trations following the high carbohydrate test meal and the fifth hour glucose concentrations were significantly below fasting concentrations. Blood pyruvic acid changes were slight following the high fat test meal* following the high carbohydrate test meal, blood pyruvic acid increases from fasting were significantly lower among the overweight than among the average weight subjects. Following the high fat test meal, chylomicron concentrations showed a significantly earlier rise, reached higher peak values and decreased more rapidly toward fasting among the underweight than among the overwei^it subjects; there were no significant group differences in serum total lipid concentrations. Following the high carbohydrs.te test meal, serum total lipids and/or chylomicron concentrations were increased above fasting among the overweight subjects but not among the average or underweight subjects; mean serum total lipid increments were greater among the overweight subjects following the high carbohydrate than following the high fat test meal. The results appeared to indicate that the overweight women had a delayed utilization of carbohydrate of the test meals, whereas the under­ weight women showed some greater preference for carbohydrate in metabolism. METABOLIC PATTERNS 01' A GROUP OF OVERWEIGHT, UNDERWEIGHT AND AVERAGE WEIGHT WOMEN By Betty Eileen Hawthorne A THESIS Submitted to the School of Graduate Studies of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of DOCTOR OP PHILOSOPHY Department of Foods and Nutrition 195^ ProQuest Number: 10008328 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10008328 Published by ProQuest LLC (2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 4 8 10 6 - 1346 ACKNOWLEDGMENTS The author wishes to express her appreciation to the members of her Guidance Committee for their interest and advice; to the several inembers of the Foods and Nutrition Department who assisted in the in­ vestigation; to Dr. Leo Katz of the Mathematics Department for his suggestions for statistical analyses; and particularly to the twentyone women subjects for their interested cooperation and to Dr. Wilma D. Brewer for her constant encouragement, guidance and counsel. The author acknowledges with gratitude the research grant from the Michigan State College Fund and financial assistance provided by Public Act 346 during 1951 through 1953 and a Graduate Council Fellow­ ship during 1953. TABLE OF CONTENTS Page ...................................................... 1 REVIEW OF LITERATURE.................................................. 6 Patterns of Energy Metabolism................................... 6 Basal m e t a b o l i s m .............................................. 7 INTRODUCTION. Specific dynamic action of food.................................. 14 Respiratory quotients............................................ 19 Blood P a t t e r n s ..................................................... 26 Blood sugar concentrations...................................... 26 Blood l i p i d s .....................................................30 Blood pyruvic a c i d ....................................... 42 Blood ketones..................................... 43 Urinary Patterns of the Obese and L e a n ........................... 44 Summary............................................................. 46 THE INVESTIGATION....................................................... 48 Experimental P r o c e d u r e ............................................ 48 Experimental plan................................................ 48 S u b j e c t s ......................................................... 49 Test m e a l s ....................................................... 53 Experimental m e t h o d s .............. $6 Collection of samples and experimental data................... 56 Analysis of expired air samples................................ 60 Hematological measurements ................................. 60 Page Chemical methods of blood analysis ................... 61 Blood glucose................................................. 6 l Blood pyruvic a,cid.......................................... 62 Serum alkaline p h o s p h a t a s e .................................. 65 Serum total cholesterol...................................... 65 Serum total l i p i d s ........................... 66 Chemical methods of u r i n a l y s i s ................................ 68 Counting of c hylomicrons...................................... 69 Analysis of dietary d a t a ...................................... 73 Statistical treatment of data.................................. 73 The Use and Verification of the Kofranyi-Michelis Respirometer . 73 RESULTS AND DISCUSSION................................................... 86 Classification of Subjects ...................................... 86 Food Intake P a t t e r n s .............................................. 89 Energy Metabolism................................................. 104 Basal energy expenditures....................................... 104 Energy expenditures following testm e a l s ....................... 108 Bases of expressions of energy expenditures................... 114 Non-protein respiratory quotients............................... 119 Energy metabolism patterns: Summary of observations ........ 124 Blood Sugar Concentrations....................................... 125 Fasting concentrations ........................................ 125 Responses to test meals......................................... 128 Page Serum Lipid P a t t e r n s .............................................. 135 Fasting serum lipid concentrations ........................... 135 Serum total lipids and chylomicron concentrations following test meals . . ....................................... 145 Blood Pyruvic Acid Concentrations. ...................... 162 Fasting concentrations . . . 162 Following test m e a l s .............. l64 Fasting Serum Alkaline Phosphatase Concentrations................ 169 Urinary Patterns ............ 172 Urinary albumin, sugar and acetone "bodies...................... 172 Urinary nitrogen excretions..................................... 175 Between-Day Variations in Fasting Values ....................... 181 Interrelationships of Metabolic Factors. 182 Discussion . ..................... ............................. - .................. 192 S U M M A R Y ................................................................ 198 C O N C L U S I O N S ............................................................ 206 LITERATURE C I T E D . ...................................................... 207 APPENDIX................................................................ 220 Tables .................................................... 221 Case H i s t o r i e s ............................. 244 Directions for Subjects........................................... 251 Diet H i s t o r y ...................................................... 252 Medical History.................................................... 257 LIST OF TABLES Table I II Page Anthropometric data and evaluated body builds of subjects . 50 The ages, heights and weights of subjects classified according to body weight...................................... 5 /+ III Composition of test m e a l s .................................... 55 IY Calibrations of concentration changes of carbon dioxide and oxygen during the collection in rubber bladder of six minute expired air samples................................ 78 Y Calibrations of concentration changes of carbon dioxide and oxygen during the collection in rubber bladder of eight minute expired air samples.............................. 80 YX VII VIII IX X XI XII Calibrations of the metering device of the KofranyiMichaelis respirometer............... 8h Summary of clinical, hematological and medical history data of all subjects.......................................... 90 Contributions of protein, fat and carbohydrate to calorie intakes of single random day diet records ........ 99 Mean contributions of protein, fat and carbohydrate to calorie intakes of single random day diets ............ 100 Total fat and carbohydrate intakes of individual subjects for twenty-four hours preceding experimental days ........ 103 Mean energy expenditures at intervals on two test days. . . 107 Mean calorie expenditures above basal during five hour periods following two test meals................ 112 XIII Mean non-protein respiratory quotients at intervals on two test days..............................................120 XIV Mean blood glucose concentrations at intervals on two test d a y s ................................................ 130 XV Mean fasting serum lipid constituents ..................... 139 Table XVI Page Distribution of subjects according to fasting serum lipid fraction concentrations ............................. iMZ XVII Mean capillary serum chylomicron counts at intervals on two test days............................................ Id? XVIIX Mean capillary serum total lipid concentrations at intervals on two test d a y s , ............................... 15*+ XIX Mean capillary serum total lipid concentrations expressed as percentage of fasting concentrations ................... 155 XX Mean blood pyruvic acid concentrations at intervals on two test d a y s .............................................. 165 XXI Qualitative tests for urinary albumin, sugar and acetone bodies at intervals on two test days....................... 173 XXII Mean urinary nitrogen excretions at intervals on two test d a y s .................................................. 17& XXIIt Total urinary nitrogen excretions during five hours following two test meals................................... 179 XXXV Summary of the mean differences between experimental days in fasting values of various metabolites and metabolic products.................................................... 183 XXV XXVI XXVII Calculated daily intakes of calories, protein, fat and carbohydrate by meals ...................................... 221 Pulse rates at intervals Volume on two test d a y s ............... 226 of expired air at intervals on two test days . . . . 22? XXVIII Overall respiratory quotients at intervals on two test days.........................................................228 XXIX lion-protein respiratory quotients at intervals on two test d a y s .................................................. 229 XXX Oxygen consumption rates at intervals on two test days. . . 230 XXXI Energy expenditure rates at intervals on two test days. . . 231 XXXII Cumulative calorie increments for five hours following two m e a l s .................................................. 232 Table XXX til Page Hourly calorie expenditures at fasting and at intervals following high carbohydrate test meal according to various methods of expression ...................................... 233 XXXIV Blood glucose concentrations at intervals on two test days. . . .................................................... 235 XXXV Serum total lipid concentrations at intervals on two test d a y s .................................................... 236 XXXVI Serum chylomicron counts at intervals on two test days. . . 237 XXXVII Fasting serum cholesterol concentrations on two test days . 238 XXXVIII Fasting serum lipoprotein concentrations............. 239 XXXIX Blood pyruvic acid concentrations at intervals on two test d a y s ..................................... 2hl Fasting serum alkaline phosphatase concentrations on two test d a y s ................................. 2*+2 XL XLI Hourly and cumulative urinary nitrogen excretions at intervals on two test days................................... 2*+3 LIST or FIGURES Figure page 1 Influence of expiration rate during six-minute periods of collection of expired air on percent carbon dioxide remaining in rubber 'bladder of Kofranyi-Michaelis respirometer................................................... 81 2 Influence of expiration rate during eight-minute periods of collection of expired air on carbon dioxide remaining in rubber bladder of Kofranyi-Michaelis respirometer. . . . 82 3 Regressions of basal hourly energy expenditures on percent deviations from desirable weight for twenty-one women on two test d a y s ............................................... 105 h Hourly energy expenditures at intervals on two test days. . 110 5 A comparison of mean hourly calorie expenditures according to various methods of expression.................. 117 6 Non-protein respiratory quotients at intervals on two test d a y s ............................................... 122 7 Blood glucose concentrations at intervals on two test days.......................................................... 129 8 Fasting serum total cholesterol concentrations for twenty-one women on two test days in relation to percent deviations from desirable weight............................. 137 9 Fasting serum lipoprotein class concentrations in relation to percent deviations from desirable weight ............... 138 10 Chylomicron counts at intervals on two test days.............Ih6 11 Serum total lipid concentrations at intervals on two test d a y s .................................................... 152 12 Blood pyruvic acid concentrations at intervals on two test d a y s .................................................... l66 13 Fasting venous serum alkaline phosphatase concentrations for twenty-one women on two test days in relation to percent deviations from desirable weight.................... 171 Hourly urinary nitrogen excretions at intervals on two test d a y s .................................................... 177 Multiple variable scatter diagrams of fasting hourly energy expenditures, non-protein respiratory quotients, blood glucose, blood pyruvic acid, serum total lipids and hourly urinary nitrogen excretions for twenty-one women on two test days.......................................... i8h Multiple variable scatter diagrams of increments from fasting of energy expenditures, blood glucose, blood pyruvic acid, serum total lipids, and hourly urinary nitrogen excretions in relation to non-protein respiratory quotients for twenty-one women at the first hour following two test meals............................................ 186 Multiple variable scatter diagrams of increments from fasting of energy expenditures, blood glucose, blood pyruvic acid, serum total lipids, and hourly urinary nitrogen excretions in relation to non-protein respiratory quotients for twenty-one women at the third, hour following two test meals............................................ 188 Multiple variable scatter diagrams of increments from fasting of energy expenditures, blood glucose, blood pyruvic acid, serum total lipids, and hourly urinary nitrogen excretions in relation to non-protein respiratory quotients for twenty-one women at the fifth hour following two test meals............................................ 189 Summary of mean metabolic patterns for overweight, average weight and underweight subjects ................. 201 INTRODUCTION The causes and characteristics of obesity and leanness have long been of interest to nutritionists. That obesity and leanness represent dis­ proportions between caloric intakes and caloric expenditures has been an axiom of energy metabolism since the time of Yoit. From earliest times food scarcity has been the predisposing factor to caloric undernutrition. Overeating is recognized as the basic cause of obesity. Historically, overeating in times of plenty as insurance for an uncertain future was often a wise course of action. today. This may also be true in some cultures Currently, however, an excess of body weight is more commonly con­ demned as none of the subtler and more serious health hazards of our time” (Armstrong, et al., 1951)* Obesity is regarded as an increasingly serious health problem in this country (Ibid) and in Great Britain (Meiklejohn, 1953). The striking increases of mortality and morbidity rates with increasing degrees of overweight have been well established (Armstrong, et al., 1951). Downes (1953) has recently compiled new evidences of the significant association of heart disease, hypertensive vascular disease, arthritis, diabetes and gall-bladder disease with overweight states. Other associated degenerative conditions such as cancer, nephritis, atherosclerosis, toxemia of pregnancy, cirrhosis of the liver, emphysema and varicose veins, are frequently cited (Gastineau, Rynearson and Irmisch, 19^9). An underweight state is less strikingly related to disease and increased mortality. Although an increased incidence of tuberculosis in -“2- underweight adolescents and young adults has been observed, Keys (1950a) stateds wSevere undernutrltion seems to be beneficial, if anything, in the so-called degenerative diseases®. Animal studies of McCay (l9*+7), Riesen, et al, (l9*+7) and others are of interest in this regard, because these studies demonstrated that increased longevity accompanied life-time restrictions of caloric intakes, particularly restrictions of carbohydrate intakes. Research on obesity has been extensive in recent years with particular attention directed toward an increased understanding of the underlying cause or causes of overeating. Appetite control is generally recognized as the result of interrelations and interactions between humoral substances, both endocrine and non-endocrine, certain nerve centers in the hypothala­ mus , and subconscious and conscious areas of the cortical region of the brain. The amazing accuracy of the appetite as a regulator of caloric balance in the majority of people under varied circumstances has been emphasized by many, e.g. Keys (1950a) and Newburgh (1950)* Overeating by others has been ascribed to a wide variety of causes; evidence for some causes is well defined, whereas for others there is still considerable controversy. Current theories of causes of overeating may be classed generally as environmental, psychological, physiological (endocrine and non-endocrine) and constitutional. The influences of the senses, emotions, habits and training on food selection have been cited as strong environmental and neural factors (Oastineau, et al., 19*0; McCance, 1953; Mayer, 1953b) and the association of certain psychologic patterns with states of obesity have been reported both in children and in adults (e.g. Bruch, 19*0; Kotkov and. Murawski, 1952). That dysfunction of nervous elements associated with the hypothalamus is capable of producing a marked increase in desire for food has been substantiated by numerous experiments in which animals have been subjected to hypothalamic lesions. by Mayer (1953). These studies have been reviewed The importance of the functioning of the hypothalamus in appetite regulation in the control animal is less well defined, but the sensitivity of the hypothalamic nerve centers to humoral (McCance, 1953) and nervous (Mayer, 1953b) stimuli has been Investigated. Physiologically, the existence of metabolic anomalies as hypoglycemia, lipophilla and hypolipemia has been held responsible for desires to eat excessively, presumably due to decreased or delayed satiety (Bulatao and Carlson, 192**; Wilder and Wilbur, 1938; Bauer, 19**1; Wilder and Sprague, 19**5) , but the mechanisms of the reactions have not been satisfactorily defined. Recently arteriovenous glucose differences, rather than simple hypoglycemia, have been correlated with hunger in both animals and humans and the glucostatic theory of appetite regulation has been proposed (Mayer, 1953a). According to this theory the hypothalamic glue or ecep tors are Influenced by ®effactive sugar levels®, which in turn are regulated by a hyperglycemic, glycogenolytic hormone. The effects of several endocrine factors, from the pancreas, adrenals, thyroid, pituitary and gonads, upon tissue and blood constituents, which in turn may affect the hypothalamus or other nervous centers are recognized. Blood glucose and lipid concentrations also have been associated with differences in the rates of transformation of carbohydrate into fat (Hagedorn, Holten and Johansen, 1927; Strang and McClugage, 1931. Lyon, Dunlop and Stewart, 1932) and qualitative and quantitative -in­ differences in the overall or preferential ability of the tissues to meta­ bolize different foodstuffs (Brooks, :i946; Gilmore and Samuels, 1949; Pennington, 1 9 1953b). The concept of adipose tissue as an active tissue with special metabolic functions subject to neural control instead of a relatively inert reserve (Rose, Stern and Shapiro, 1953i Wertheimer and Shapiro, 1948) has contributed to the conclusion that abnormally functioning fat storage mechanisms might result in hypolipemla (Pennington, 1953a; Wilder and Sprague, 1945) . That greater total efficiency in the digestion and absorption of foodstuffs is not a factor is commonly agreed (Wilder and Wilbur, 1938; Newburgh, 194-4; Brooks, et al., 1946; Thomas and Friedman, 1949; Mitchell, 1952). Although obesity, which is uncomplicated by endocrine dystrophy, lias not been shown to be associated definitely with a lowered specific dynamic action of food or with a lowered basal metabolism, expressions as "degree of utilization of metabolizable energy*® (Deuel, et al., 1947), "wasteful expenditure of energy15 (Brody, 1945) and “economy of utilization” (Forbes, et al., 1946a, 1946b) have been applied to describe differences in specific dynamic action observed under varying experimental and natural conditions. Mitchell (1952) proposed that the efficiency of the homeostatic mechanisms of appetite control and the conversion into heat of food which is consumed above current needs may vary with constitutional types. stated; He "Differences between endomorphy and ectoaorphy in disposition of food energy may rest not so much in the peak dynamic effect as in its duration15. Metabolic individuality was emphasized also by Conn (1944) in his observation that the same endocrine dysfunction may not affect the energy balance of two individuals in the same way; however, he -5-= concluded, wwhtle the Influence of environmental factors is well established, there is little positive information presented for the case of "hereditary obesity" in humansM . Keys (1950®-) discussed the Incidence of caloric undernutrition or semi starvation in the United States as being primarily amongs l) persons with appetite failure from either psychic or physical reasons, z) persons with impediments to food ingestion or digestion, and 3) persons with abnormal avenues of caloric loss, e.g. febrile states and hyperthyroidism. Appetite controls or homeostatic mechanisms responsible for the habitual mild caloric undernutrition of the lean in the presence of an adequate supply of food are no more clarified than those operating toward the development of obesity. Metabolic qualities associated with obesity and leanness have received less emphasis than causal factors. Etiological studies* however, have yielded data on individual factors of metabolic patterns of the obese, and, to a lesser extent, of the lean, which deviate from those found in average weight individuals. Still* the question as to whether or not there are basic differences in the physiology and the biochemistry of the overweight or the underweight individual as compared to the individual of average weight has not been satisfactorily answered. This study was planned therefore to Investigate further possible bio­ chemical differences in the metabolism of fat and carbohydrate among women of average, above and less than average body weight through simul­ taneous respiration studies and analyses of various blood and urinary constituents before and following test meals of high fat and high carbo­ hydrate composition. REVIEW OP LITERATURE A review ©f the literature on obesity and. leanness revealed that attention during the late nineteenth and early twentieth centuries was centered largely about etiology. Interest in caloric nutrition as a whole then waned with the discovery of the vitamins and the emphasis on vitamin research which followed. By the early 19^0's» food shortages in certain areas of the world, coupled with an increasing incidence of obesity in others, stimulated a renewed interest in energy metabolism, par­ ticularly in caloric Imbalances, Causes still were stressed, but effects and metabolic qualities associated with caloric imbalances began to receive more emphasis. An attempt has been made in this review to compile reported evidence of metabolic qualities associated with obesity and leanness, with par­ ticular emphasis on metabolic patterns in women. Such a review increases one's recognition of the many interrelated factors in metabolism as a whole and in energy metabolism in particular. Patterns of Energy Metabolism There is general agreement that the total energy expenditure in performing a measured amount of work by the obese individual is greater than that expended by a person of average weight but of similar age, height and sex (Keys, 1950b; Newburgh, 1950; Meiklejohn, 1953; Pennington, 1953c). Similarly, the lean individual expends less total energy for a given task than the person of average weight but of the same age, height and sex. There is less agreement concerning differences in basal metabolic rates and specific dynamic effects of foods in overweight and underweight individuals when compared to those of average weight. The existence of differences in preferential metabolism of carbohydrates or fats by individuals of differing body weights also is debated. Basal Metabolism It is generally recognized that the total basal energy expenditure of obese individuals without endocrine disorder is higher than average. Basal metabolism data, however, have been expressed in terms of various bases by different investigators in attempts to relate total metabolism te active tissue. Per unit of height the obese individual has a greater heat production than a person of average weight; the lean individual has a lower heat production. Per unit of weight obese individuals have less heat production than the average, lean individuals have more. Neither height nor weight alone, however, has been found to be a reliable basis of comparison of metabolic rates even among persons of average weight. Early experiences, particularly the early studies of Rubner and Lusk, led to the selection of heat production per square meter of body surface as the most satisfactory basis for comparisons. In 193^ DuBois summarized the studies on basal metabolism in the underweight and the obese as well as those used in establishing basal metabolism standards. Moderate caloric undernutrition did not seem to result in much deviation of basal metabolic rates from averages in either adult men or women when surface area calculated on actual weight was used as & basis of comparison. Studies on underweight women which were reviewed showed only slight average deviations: twenty-three distinctly underweight young women in the Harris and Benedict series aTeraged 1,8 percent helow the overall mean determined; seven subjects averaged =0*3 percent of the mean in another study; six subjects in another laboratory deviated 4 7.7 percent from controls; in a further group, nine underweight women averaged 4 2 percent of the mean of the group; and, in ninety-six college women who were studied, the underweight averaged =1*3 percent ©f Harris-Benedict standards or showed ^essentially no difference from those of normal weight women in the same areas*. Commenting on the similarity of basal metabolic rates in the under­ weight and the average weight individual, Keys and co-workers (1950) stated "The basal metabolic rate of apparently normal underweight people is of great interest in view of the decreased basal metabolic rate produced by semi-starvation. It is possible that a reduction in metabolic rate is associated with the process of weight loss and normal rate is associated with caloric equilibrium111. Declines of basal metabolism during caloric undernutrition have been demon­ strated both in average weight individuals (BuBois, 193&; Taylor and Keys, 1950) and in the obese (Strang and Evans, 1929; Brown and Ohlson, 1946), However, decreased basal metabolism in the post-reduction maintenance period of obese women also has been reported (Brown and Ohlson, 1946). In the obese basal metabolic rates per square meter of body surface based on actual weight have frequently tended to be subnormal but the decreases were inconsistent and often not significant (e.g. Gastineau, et al., 1949; 2fewburgh, 1950; Mitchell, 1952). Among the studies reviewed by DuBois (1936) were the following in which the basal metabolic rates per square meter of actual surface area of obese persons were compared with those of average weight. Boothby and Sandiford measured basal heat production in ninety-four obese patients and found that rates -9- were within 10 percent of average in seventy-six (81 percent). Strouse, Wang and Dye compared the metabolic rates of seventeen overweight men and women with sly average weight and nine underweight subjects and found essentially no differences, Grafe found only three out of one hundred and eighty cases of extreme obesity showed a definite decrease in metabolic rate. Basal metabolic rate also has been expressed per square meter of surface area based on ideal weight (weight at average weight for height) rather than actual weight. Expressed in this way basal metabolic rates of the obese were frequently high (Keys and Brozek, 1953). Interpretations of basal metabolic rates based on surface area calculated from either actual or ideal body weight have been criticized. The ’’surface area law” as commonly applied has been criticized by Pennington (l951a>) for obscuring differences that may exist between the lean and the obese because the ’’law" was developed as a law of uniformity equating the variables of differences in weight. Many workers have agreed that surface area is not a satisfactory unit for the expression of basal metabolism. Benedict and Talbot (1921) recognized that the body surface area was an empirical formula, although it was accepted as the best answer at the time for a numerical estimate of body mass. The problems of actual measurements of surface area are many and relatively few such measurements have been made. In estimating surface area DuBois (1936) pointed out that it was unimportant whether one used a formula based on power of body weight (the two-thirds power being an approximation ©f surface area) or a ^linear formula ’0 involving both height and weight, in dealing with persons of average build. Concerning the -10- estimation of surface area in the overweight and the underweight individual, BuBois (1936) stated! ®The linear formula seems to be the only one that can be applied with any degree of accuracy to people of widely differing form’". Although Eubner and Lusk (DuJBois, 1936) demonstrated the general proportionality of basal heat production of all mammals to their surface area, more recent results in studying homeotherms from mice to cattle (Brody, 19^5) have indicated that the metabolic rate per unit of surface area tends to increase with size. Brody (ibid) found that metabolism was expressed more uniformly as the 0.73 power of body weight; fasting 0 73 home©therms averaged 70.5 calories of heat per kilogram * ^ per twentyfour hours. Kleiber (19^7) suggested the 0.75 power of body weight and stated! ®At present there seems to be no sufficient reason against the intraspecific application of the three-fourths power rule of metabolic rate. Modulating factors for age and specific stature may be incorporated into prediction equations for human metabolic rate based on the three-fourths power rule®. Eecently ®lean body mass*, the 58fat-free body® or *°active tissue mass® have been proposed as more appropriate physiological reference standards for basal metabolism (Behnke, 1952; Keys, et al., 19501 Keys and Brozek, 1953; Miller and Blyth, 1952). Methods for the assessment of the ®fat-free body® by indirect estimates of body fat using 1) anthropometric data, including skinfold measurements and roentgenograms, 2) body density, 3 ) total body water, and h) fat-soluble indicator© have been reviewed (Keys and Brozek, 1953). £he percentage of body fat was found te increase with age, to be higher in women than in men, to be lower in the physically active than in the sedentary and to vary with body build. -11- In an investigation of the relative effects of the (!)fat-free bodyw and surface area as bases for expressing basal metabolism, Miller and Blyth (1952) reported no significant differences in the correlation co­ efficients between basal oxygen uptake and gross body weight, body surface or the fat-free body weight among a group of university students. Using similar subjects for a similar study, Keys and Brozek (1953) also reported no significant differences. When subjects with greater extremes of fatness were used, however, the Minnesota workers (ibid) found the greatest constancy of basal metabolic rate when basal metabolism was referred to units of fat-free body mass or of active tissue. Apparent differences of basal metabolic rate in age and in sex were reduced markedly when rates were referred to the fat-free body determined by dens Itome trie measure­ ments. The mean percent of body weight as fat in MnormalM women (93*3 to 97.2 percent of standard weight) was estimated as 26.5 • 30-5» 3^*5 and 38*5 for ages twenty-five, thirty-five, forty-five and fifty-five years, respectively; the determined percentages of fat content at the same ages In men were 13*1* 17*3. 21.6 and 25*9, respectively (Brozek, Pei Chen, Carlson and Brenczyfc, 1953)* A further study was made of the basal metabolism of one hundred and thirty-five clinically healthy young men who ranged in weight frem 75*6 wei^t. 151*5 percent of standard average body Although the basal metabolic rate per kilogram of gross weight decreased from underweight to overweight subjects, the differences largely disappeared when body weights were corrected for differences in fat as estimated from skinfolds or from body density. The authors stated? wHence it appears that the intensity of the basal metabolism per unit mass of non-fat tissue in the body is not reduced with increasing obesity®. -12- This conclusion I a in agreement with that of earlier investigators who found no appreciable decrease in basal metabolic rate with increasing degrees of adiposity when metabolism was referred to surface area. The question arises, however, whether the “fat-free body® or the fatfree body corrected by estimated extracellular fluid and bone mineral to “mass of active tissue® is yet the true physiological basis for comparisons of metabolic activities of tissue. Adipose tissue has been recognized as having some small but definite oxygen consumption (e.g. Wertheimer and Shapiro, 19*4-8). Studies ©f Keys and Brozek (1953) have yielded data for estimating the composition of adipose tissue in obesity; they determined that the composition of the tissue mass gained b y “normal, well-fed men 89 through forced overeating, was 62 percent pure fat, 2k percent cellular matter and 1*4- percent extracellular water, and, it was suggested, that the tissue lost in reduction of obese people might be similar. The physiological description of metabelically active tissue as the “fat-free body® assumes that all metabolism of adipose tissue is related to the percent wcellular matter®. Yet a dynamic state of the fat of adipose tissue has been demonstrated (e.g. Schoenheimer, 1942). The metabolic activity of fat is slower than that of non-fat tissues of the body; yet, as the amount of adipose tissue increases, the quan­ titative contribution of fat to total metabolic activity must also increase. If the quantitative contribution of fat to total metabolic activity is at all significant, then the amount of the metabolism of fat tissue would proportionately decrease that of non-fat tissue in any total metabolism measured. If total basal metabolism expressed on the bases of the “fat- free body® or the “active mass® is similar in the old and in the young -13- adult and In the obese and in the lean individual, as Keys and Brozek have indicated, then the metabolism of non-fat tissue in the aged and in the obese adult, who have a greater proportion of fat tissue, must be less than that in the young and in the lean adult. Similarly, one might have to conclude that a lower metabolic rate exists in women than In men. That the metabolic rate of the “active mass® does alter in adults under certain physiological circumstances has been demonstrated, in 1950 Taylor and Keys reported that a decrease of oxygen consumption was observed during semi-star vat Ion in young men. The metabolic rate during six months of semi-starvation decreased 31*2 percent per square meter of body surface* 19.3 percent per kilogram of body weight and 15*5 percent per kilogram of "active tissue®. They concluded that 65 percent of the decrease in basal metabolic rate in starvation reflected the shrinkage of the metabolizing mass of tissue and that 35 percent should be ascribed t© a decrease in the intensity of metabolism. Keys and Brozek (1953) reported experimental evidence indicating that in actively developing obesity the basal metabolic rat© per unit of non-fat tissue increased. The metabolic picture in active tissue growth was likened to that in juvenile growth. Kleiber and Cole (1950) reported differences in the metabolic rate per unit of estimated “active tissue® in two strains of rats signifi­ cantly different in body size at 55 t© 100 days of age. The average metabolic rate per rat was greater for the heavier strain but the mean metabolic rates per unit of weight, per unit of weight to the threefourths power, and per unit of body surface were lower for the heavier strain. Metabolic studies of tissue slices of these two strains should -14- be interesting in view of previous findings by Kleiber (1947) that ijn vitro oxygen consumption per unit weight of liver slices of rats, rabbits and sheep decreased consistently with increasing size of the animal to almost the same extent as the metabolic rate of the animal. Whether a quantitative difference in basal metabolic activity of metabolizing tissue exists among overweight, underweight and average weight individuals has not been finally defined. it exists, it must be relatively small. Evidence would indicate that if That the total basal energy expenditure does increase with increasing degrees of adiposity has been clearly established. Specific Dynamic Action of Food Reports of measurements ©f specific dynamic effects in underweight individuals are few. Wang, Strouse and Saunders (1924) observed high values of specific dynamic action of protein in thin subjects in contrast to low values in the obese. Mason (1927) reported six cases of under­ nutrition in which the specific dynamic action showed various abnormalities that tended to disappear as the subjects approached their respective desirable weights. Strang and McGlugage (1931) compared the total calorie increment for eight hours after a test meal of 40 grams of pro­ tein, 52 grams of carbohydrate and 26 grams of fat among obese, thin and control subjects. The mean ei^it-hour cumulative increment for the underweight subjects was 67 calories compared to cumulative mean increments of 58 calories for eight obese subjects and 51 calories for five control subjects. No measurements of specific dynamic effect were made in the Minnesota human starvation study; however, Keys, et al. (1950) -15- stated, MXn. starvation or severe undernutrition the basal metabolic rate is sharply diminished....Presumably there is also a proportional reduction in specific dynamic action®. DuBois (1936) reported that Jaquet and Svenson in 1900 were apparently the first to observe a diminished specific dynamic action in obesity. Diminished specific dynamic effects in obesity have been reported by others. Wang* Strouse and Saunders (1924) found lower heat production in­ crements in obese subjects compared to those of average weight subjects after the administration of protein and relatively slight differences between the two groups after carbohydrate and fat. Kestner and co-workers (1926) reported on eighty-eight cases of “constitutional obesity®; seventy-eight had average basal metabolic rates but showed diminished specific dynamic effect while ten had depressed basal metabolic rates and showed apparently average specific dynamic effect. Mason (DuBois, 1936) reported ten cases of simple obesity in which the specific dynamic action of protein was depressed. Bernhardt (1930) found that the specific dynamic action in obesity was usually lower than average and later In appearance. Several reports, on the other hand, have indicated that the obese show nothing unusual in their specific dynamic reactions. Lauter (1926) studied a large number of patients in Germany and found no significant difference between normal controls and obese patients studied for six to eight hours after a meal of 200 grams ©f beef. McClellan, Spencer, Falk and DuBois (DuBois, 1936) made twelve calorimeter experiments ©n four obese and three normal men after meals of 300 to 500 grams of lean meat. Considerable individual variation was observed; the average surplus heat - 16- output for the obese was reported as 13 percent compared wJ th 17 -norcent for average weight individuals. Twenty obese and twelve controls showed no essential difference in specific dynamic action, when based on total heat produced for five hours after test meals (Bowen, Griffith and Sly, 193*0. Variations which have been reported may be due in part to differences in the interpretation of data and the length of time in which caloric responses were measured. Strang and McClugage (l93l) demonstrated the fallacy of expressing specific dynamic effects as a percent of basal calories rather than as specific calorie increments above a base line with the following examples a ten calorie increase represents a l6 per­ cent increase ever basal to an individual with a sixty calorie per hour basal, whereas a ten calorie increase represents only an 11 percent in­ crease te an individual with a ninety calorie per hour basal. Since obese individuals produce more basal heat, their response te a test diet appears lew on a percentage basis. Similarly, heat increment data expressed per square meter of surface area can be misleading. Strang and McClugage (ibid) emphasized the hourly irregularities observed for their subjects and agreed with Benedict and Carpenter (1913) that the truest evaluation of dynamic effect was gained by measurement of the total increment. Few investigators, however, have been able to continue measurements throughout the duration of dynamic effect, which may last twelve hours or more. Recently Mitchell (1952) has reaffirmed the importance of the measurement of total heat increment by stating that a difference between endoraorphy and ectomorphy may rest net so much in peak but rather in total dynamic effect. -17- Individual variation in specific dynamic effect has occurred in all studies and has been a complicating factor in the interpretation of results. Newburgh (19*44), in summarizing a number of studies, emphasized the inconsistent results found in humans of all body types. DuBois (1936) stated, "It is notoriously difficult t© establish good curves showing the specific dynamic action of food88. Because ©f the variations observed in studies of specific dynamic action and the relatively small increments measured in all subjects, the differences that have been found have been minimized with the argument that they were quantitatively too small t© account for the gains or losses in weights of the overweight or the underweight individual. For examples “The average normal increase for the day caused by food is only about 6 percent of the total metabolism and if it were halved or abolished it would not account for the enormous discrepancies between the alleged food intake and weight changes reported by some observers98, (DuBois, 193&)* This same thought has been reiterated by Newburgh (l9^2b; 19^4; 1950). Tet it is possible that differences among individuals in the heat increment in response te feed may represent seme significant qualitative difference in metabolic pattern of energy metabolism, even though it may net account quantitatively for gains or losses of weight. Support for this hypothesis was provided by Forbes (l9^b) who stated that measurements of specific dynamic action of nutrients based on heat production above fasting level are without definite significance as measures of energy expense of nutrient utilization. Forbes and ce- workers (ibid), Brody (19^5) and others have considered that in animals the heat production of fasting actually comprises a net energy or an energy expense of utilization exactly as does metabolizable energy of food origin. A part of the energy value of nutrients fed to fasting animals is to spare the catabolism of body nutrients. Therefore the observed heat production is less than the true energy expense of utilization. Individual differences in metabolic pattern might result then in individual differences in the heat increment response measured after a given test meal. Recent reports by Fenton and co-workers on differences in oxygen consumption in response to food intakes in twe strains of mice are per­ tinent (Fenton and Carr, 1951; Fenton and Dowling, 1953; Lyon, Dowling and Fenton, 1953)* la 1951 a marked strain difference In mice was noted in response te various amounts of fat in the diet. Two strains increased their rate of weight gain with increasing fat contents of the ration; twe strains showed ne further increases in rates @f weight gain when the fat content was increased above 15 percent. showing that both and In 1953 data were presented strain mice would consume more calories when fed a $0 percent fat diet than when fed a 5 percent fat diet, both fed ad libitum. “Mice of the strain responded to the increased caloric intake with increased oxygen consumption and thus presumably increased heat production. The G^H strain showed no increase in oxygen uptake, a factor likely to contribute t© the obesity so readily induced in this strain" (Lyon, Dowling and Fenton, 1953) • In discussing the current concepts of specific dynamic action which ascribe the extra heat incident to the utilization of food to Inter­ mediary chemical and physical processes, Brody (19^5) summarized the following as factors which affect the heat increment: the balance of nutrients (absence of a limiting component); the general plane of nutrition (higher on high levels); the environmental temperature (less -19- in low temperatures); whether the nutrient is stored or otherwise u s e f u l l y employed; muscular or other productive activity; and age. With respect to previous diet, DuBois (1936) observed: “Under-nourished individuals or those who have for any cause diminished glycogen stores in the liver give curves that are quite different from those of well-nourished subjects who have previously been on a high carbohydrate diet. . . This fact has been overlooked in a great many studies of the specific dynamic action". The measured dynamic effect of a nutrient is affected therefore by the nutrient combination in which it is metabolized and the method of disposition of absorbed nutrients by the individual as well as by the technique of measurement. Small differences in measured dynamic effects may have significance in evaluating qualitative differences in metabolic patterns in energy metabolism. The various factors influencing measured dynamic effects may mask any differences associated with different weight groups, however. Respiratory Quotients Attempts to evaluate the type of energy metabolism occurring at any time still center in determinations of respiratory quotients. A high respiratory quotient is interpreted as indicating a predominance of oxidation of carbohydrate; a low respiratory quotient is interpreted as indicating a predominance of oxidation of fat. Soskin and Levine (1952) discussed the composite nature of the measured respiratory quotient of intact animals or men and showed that the respiratory quotient of the whole body is a combination of different respiratory quotients which arise in the various organs and tissues; the respiratory quotients of the individual reactions may range from 0 to 8.0. The individual respiratory quotients are derived from multiple interconversions of organic radicals as well as from purely catabolic oxidations; hence, the authors concluded that the total or average respiratory quotient could not represent merely the kind and amount of foodstuff being oxidized. Despite its inherent limitations as a quantitative index of the type of food that is being completely oxidized, the composite respiratory quotient can indicate the trend of the reactions which are occurring, a trend which has been called, “the final displacement in the carbohydrate balance and fat balance during metabolism" (Forbech, 1938). In 1925 Wang, Strouse and Saunders studied the qualitative aspects of energy production in the basal state and post-prandially in obese subjects and concluded from the higher than usual respiratory quotients observed after eating that the obese oxidized less fat than did people of average weight* lu * review of these data, Hagedorn, Holten and Johansen (1927) questioned the interpretation of the investigators and assumed rather that the higher elevations represented a more rapid than usual rate of transformation of carbohydrate into fat. In their own study among thirty obese and fourteen control subjects large individual differences In fasting respiratory quotients were observed, but they also noted that the mean respiratory quotient in the obese was lower than that of their control subjects. Further, they observed a relation between the percentage overweight of their obese subjects and the respiratory quotient; the more overweight subjects had particularly low respiratory quotients. Forty single determinations of fasting respiratory quotients in normal subjects following two days on high carbohydrate intakes averaged 0 .86h with 13 percent below 0 .825; fifty-eight single “ 21 " determinations on obese subjects under similar circumstances averaged 0 .8 l6 with 59 percent below O. 825 . In a later report, Hagedorn (1928) made further observations on studies previously reported from his laboratory. In obese patients with a respiratory quotient below 0.825 the mean basal metabolic rate was 45 percent, whereas in the group with basal respiratory quotients above 0.825 the mean metabolic rate was 40*5 percent. He con­ cluded that in obesity one is dealing with two factors, usually not found together: a difference in type and a difference in quantity of metabolism. Strang and McClugage (1931) determined respiratory quotients as a part of a study of the specific dynamic action of food in abnormal states of nutrition. Fasting values obtained from seven obese patients ranged from 0.698 te 0 .830 , averaging 0 .757» whereas values of controls ranged from 0.770 te 0.8**8, averaging 0.783* These same people were studied again after a test meal of h0 grams of protein, 26 grams of fat and 52 grams ef carbohydrate; respiratory quotients were determined at the first, second, third, fourth, sixth and eighth hours. The average values obtained for the controls were 0 .838, 0 .810, 0.80^+, 0.823, 0 .812 , and 0.819 and for the obese respectively. were 0.7^6, 0 .772 , 0.752, 0.7^0, 0 .761 , and 0.795, It Is difficult to state whether or not the fact that the ebese subjects were all hospital patients who had been on a reducing regimen for varying periods of time might be a factor in the differences in responses observed. That previous high fat or high carbohydrate intakes influence fasting respiratory quotients has been observed by many. The influence of quantitative differences in the previous diet, which would also influence the quality of the metabolic mixture, was indicated by the data of Lyon, Dunlop and Stewart (1932). These investigators -22- also reported on obese subjects who were under treatment; the subjects were patients in the Royal Infirmary, Edinburgh. Data accumulated over many months showed that, whereas the basal metabolic rate was generally within normal limits, although somewhat lower than average, the respiratory quotients were usually low and often below 0.70. The average respiratory quotient of thirty-four determinations was 0.755 for subjects on 2,000 t© 2,500 calorie diets; on 1,000 t® 2,000 calorie diets, the respiratory quotients averaged 0.721. The authors interpreted the low respiratory quotients of their obese subjects as evidence of the formation of car­ bohydrate from fatty acids. There was no assumption that carbohydrate was not being oxidized, only that it was being produced at a more rapid rate than it was being oxidized. It was noted that ketonuria did not accompany the respiratory quotients observed below 0.70. When the respiratory quotient was determined for these subjects after a carbohydratecontaining meal (66 grams of protein, 38 grams of fat and 100 grams of carbohydrate), abnormally high respiratory quotients were not obtained; the respiratory quotients were greater than 0 .70 , however. Since low post-absorptive respiratory quotients in obese subjects had been found by other workers, Bowen, Griffith and Sly (193*0 inves­ tigated the "possibility that a qualitative metabolic variation exists in the obese person" by measuring the effect of a high fat meal on the respiratory quotient. A high fat meal was selected for their study, since in preliminary tests no differences were found in their subjects following protein and glucose ingestion; one of the first obese subjects to bo studied, however, showed a consistent rise in respiratory quotient after a fat meal. Twelve control subjects, six of whom were slightly -23- underweight, and twenty non-diabetic obese subjects, averaging 81 percent overweight (56 - 169 percent), were fed a test meal containing 128 grams of fat immediately after the determination of fasting respiratory quotients. Fasting respiratory quotients ranged from 0.7& te 0.88, averaging 0.825, in the control subjects and ranged from 0.72 to 0 .83 , averaging 0 .765 , in the obese. The two groups shewed no real difference in response during the six hours following the meal; in general, there was no change in the respiratory quotient at the first hour, a depression occurred from the second to the fifth hour and at the sixth hour there was a slight rise in value. The amount of fat fed was exceedingly large which might have obscured any possible differences in preferential use. A report of respiratory quotients observed in the experimental hypothalamic obesity ©f rats (Brooks, 1946) compared the basal respiratory quotient during the dynamic and static phases of obesity: "During the dynamic phase of obesity the ingestion of food or glucose solutions by the obese rats raised the respiratory quotient above unity. During the static phase the respiratory quotient responses to f©ed and glucose ingestion were not essentially different from those of normal animals". Basal respiratory quotients of hypothalamic obese animals, however, were not significantly different from those of normal controls. Similar results have been reported by Mayer (1952) in the hereditary-obesity syndrome of mice studied in his laboratory. Fasting respiratory quotients were normal whereas non-fasting respiratory quotients were higher than normal. The author interpreted these data as indicating an increased rate ef lipegenesis. The higher post-prandial respiratory quotients of animals in the dynamic phase of obesity were similar to those observed by Wang, Strouse -24— and Saunders (1925) In their obese human subjects. The post-prandial quotients of the obese subjects studied by Strang and McClugage (1931) did not show similar elevation*. It is possible that there was a difference in the phase of obesity as all of the obese subjects of Strang and Mc= Clug&ge were patients undergoing weight reduction treatment. However, Bowen,et al. (1934) also reported no difference between control and obese subjects In respiratory quotients obtained following carbohydrate, protein or fat feeding. There apparently have been few measurements of respiratory quotients in underweight individuals. Keys, et al. (1950) feund that the respiratory quotients were not changed in the Minnesota semi-starvation experiment and ascribed the uniformity to the fact that components which were metabolized during restriction were similar to those being metabolized on a maintenance diet; the tissues supplied the supplementary portions of protein and fat. Fasting, on the other hand, had been found to result In decreases of the respiratory quotient toward 0.70 or below. Interpretations of respiratory quotients are difficult because of the composite which they represent and the ability of the body to adapt to different metabolic mixtures. The difficulty of assessing correctly the actual metabolic picture from a measured respiratory quotient is illustrated by the following (Soskin and Levine, 1952): the complete oxidation of acetoacetic acid and certain amino acids yields theoretical respiratory quotients of 1 .0 , exactly as does the complete oxidation of glucose; and, a certain fatty acid which would yield a theoretical respiratory quotient of 0.693 upon being completely oxidized would also yield a respiratory quotient of 0.693 if it were first converted to car­ bohydrate and then oxidized. -25- Adaptation ha© been emphasized by a report from Gilmore and Samuel© (19^9) on the metabolic activity of isolated rat diaphragm. Following four weeks of forced feeding of high fat or high carbohydrate diets, the diaphragm muscles preferentially utilized the products of metabolism from the major type of foodstuff which had been fed, although the ability to utilize either type had not been abolished. That preferential *1 or •"retarded85 catabolism of a foodstuff might be a factor in obesity was proposed by Brooks (19**6) in explaining the retarded mobilization of fat found in hereditary obesity of yellow mice. Yet there was no question but that the obese mice could oxidize fat because loss of weight occurred during starvation. Adaptation in man has been suggested by Rabinowitch and co-workers (Rabinowitch and Smith, 193&; Corcoran and Rabinowitch, 1937) in reports of a brief study of the Canadian eastern arctic Eskimo. The low fasting respiratory quotients without evidence of ketonuria were attributed to an unusual metabolic mechanism adapted to the high fat diet usually consumed by these subjects. A possibly similar adaptation in man has been indicated by the data of Lyon, et al. (1932). It is interesting to contemplate the extent and degree of adaptation that may exist in the metabolism of foodstuffs in view of the general physiological adaptation mechanisms currently being elucidated by Selye and co-workers (19^9) and others. Lower fasting respiratory quotients would appear to be a metabolic pattern associated with obesity in man; post-prandial respiratory quotients may very with different phases of obesity, dynamic or static, or with adaptation. Conflict in current evaluations of the qualitative metabolism of the obese is illustrated by the following two quotations’ “Since both the quotients obtained during fasting and after the ingestion of food are lower in obese subjects (noting particularly the study of Strang and McClugage, 1931). we have before us classic evidence that such persons are metabolizing more fat than the normal controls. They cannot at the same time be storing more fat or withholding more of it in depots *1 (Newburgh, 1950); and Mtheir study of respiratory quotients of normal and obese subjects in the post-absorptive period after a standard meal . . (referring to studies of Hagedorn, Hoiten and Johansen, 1927) offer circum­ stantial support to ... the •.. hypothesis that obesity in many cases might be due to an abnormally increased transformation of carbohydrate into fat which would also involve differences in S.D.A., since dietary carbohydrate transformed into fat could not contribute to the oxidative metabolism1" (Mitchell, 1952) . Blood Patterns Blood concentrations of glucose and fat have been determined in obese individuals primarily to investigate the possible roles of those factors in maintaining homeostatic mechanisms related to hunger and appetite. Similar investigations in underweight individuals have been limited. Pew reports of concentrations of other blood constituents in relation to body weight have been found. Blood Sugar Concentrations Blood sugar concentrations are influenced by a variety ©f factors and caution in the interpretation of glucose tolerance values has been emphasized. Soskia and Levine (1952) stated the problem in general termsJ “The blood-sugar level represents a dynamic balance between tho rate at which sugar is entering the blood stream from the liver and from any exogenous source and the rate at which it is being removed from the blood by the tissues of the body. Thus, a rise in the blood-sugar level may result either from an increased rate of sugar supply or from a decreased rate of sugar utilization, or from "both together. Conversely, a fall in the blood-sugar level may be due to decreased supply or increased utilization, or both. Nor is it possible to tell which factor is responsible from the mere change in blood-sugar unless one is controlled or eliminated while the other Is observed*8. Endocrine regulation, of blood sugar has long been apparent. The critical influences of the hormones of the pancreas, anterior pituitary and adrenal cortices have been reviewed (Conn, 1953). Generally it is agreed that the effect of exercise on blood sugar values is slight when exercise is moderate; however, with strenuous exercise, even of short duration, the blood concentration is raised significantly (Rakestraw, 1921). The immediate rise in blood sugar in response to strenuous exercise with a subsequent decrease, sometimes to hypoglycemic values, is typical of the general course of blood sugar in response to all stress (Selye, 19^9). Orent-Keiles and Hallman (19^9) have presented data showing highly significant seasonal differences in fasting blood sugar concentrations in nine women studied over a two year period. Although all of the figures were within generally accepted ranges of “normal88, the fasting values were higher In the winter months than during the summer months. The authors ' 1 search of the literature revealed only two previous observations of such change. Their data indicate the need for caution in comparisons of fasting blood sugar values when there is an appreciable time lapse. The previous diet pattern of an individual, particularly the carbo­ hydrate intake, frequently has been reported to have a significant influence on the glucose tolerance which is measured; previous high carbohydrate intakes increase the tolerance of an individual to a given -28- carbohydrate intake. These effects have been reviewed and restated by Beaudoin, Van itallie and Mayer (1953). Previous self-selected diets had no significant influence on fasting glucose concentrations in young adults, however (Addison, Tuttle, Baum and Larsen, 1953). The protein composition of the test meal has been found to have an important influence ©n glucose tolerance. Investigators at the University of Iowa (Ibid; Coleman, Tuttle and Baum, 1953) and Qrent-Keiles and Hallman (19^9) have presented conclusive evidence that increased amounts ©f protein in a test meal delay significantly the rate of fall of blood sugar concentrations after initial peak values are reached. These studies emphasize the fallacy of comparing carbohydrate curves determined in different laboratories following test meals in which the protein content of the diet is varied, even though the carbohydrate and fat contents might be similar. The influence ©f age ©n glucose tolerance response has been re­ ported by Schneeberg and Finestone (1952). They found that normal subjects over forty years ©f age had a decreased tolerance to intravenous glucose as compared to subjects sixteen to thirty-nine years of age. Liver dysfunction, deficient stores of available liver glycogen or a previously low carbohydrate diet were eliminated as causes. older subjects tolerated glucose well, however, As several the authors questioned “whether the older subjects 1 mean might not have been heavily weighted with potential diabetics*1. Increasing fasting sugar values with in­ creasing age in children have been reported (Mayer, 1951); gradual but not linear increases from a mean of 77 milligrams per 100 milliliters of blood at two years to 92 milligrams per 100 milliliters of blood at fifteen years were found in a study of 700 children. The influence of obesity on glucose tolerance test responses has been observed for many years; past findings have been summarized by Beaudoin, Van Itallie and Mayer (1953) • The documentation of evidence for a decreased carbohydrate tolerance associated with obesity in middle age is large. Results of studies of glucose tolerance in obesity at all ages, however, have not been consistent. Beaudoin, et al. (1953) suggested that the in­ consistency of findings may be due in part to a lack of differentiation between “active” and “static” obesity. The authors subjected the data of Despisch and Hasenohrl, 1927, Ogilvie, 1935 and Godlawski, 1 9 ^ , who had reported no consistent abnormality in the obese but who had noted ten­ dencies to secondary hypoglycemia, to a re-evaluation. A significant correlation between the activity and the duration of obesity and increased tolerance to glucose was found. In early obesity glucose tolerance curves were lower or displayed a more frequent tendency to drop to hypoglycemic values than did those of non-obese subjects or persons with arrested or long-standing obesity. From these results and from a more recent study Beaudoin and co-workers (ibid) postulated that there is a metabolic dis­ order in “active” obesity which has two mechanisms; l) increased lipogenesis and 2) decreased oxidation of fat with a proportionally in­ creased oxidation of glucose. Obese women and controls of the same sex and approximate height and age were matched and the obese subjects, whose weights ranged from 18 to 8h percent above “desirable” weight, were divided into “active” or “static” groups depending on their weight history. The controls ranged in weight from 43 to -18 percent of “desirable” weight. were similar. Previous diet patterns of the obese and the controls Blood glucose concentrations were determined at fasting -30- and at fifteen minute intervals for one hour following a self-selected noon meal on one day and following the ingestion of 50 grams of glucose on another. For the one hour period in which determinations were made the six “active” obese subjects displayed a markedly increased average tolerance both to the meal and to the glucose in comparison with the con­ trols; the “static” obese showed a normal or decreased tolerance. Considerable individual variation did occur, however. The results agreed with findings of Mayer, Bates and Van Xtallie (1952) on experimental animals in vhich increased carbohydrate tolerance occurred while weight was accumulating in animals with lesions of the hypothalamus; after obesity was established, the animals displayed normal or decreased carbohydrate tolerance. Blood Lipids Blood lipid patterns have been investigated widely but their relations to abnormal states are not well defined. Blood lipids present a more com­ plex picture than that of blood sugar because of the many constituents composing “total blood lipids” and because of the wide range of values found in apparently healthy individuals. Peters and Van Slyke (19^*6) reviewed the literature on fasting values of blood lipid constituents, which occur mainly as cholesterol, both free and es terifled„ phospho­ lipids, neutral fat and free fatty acids, and concluded that the range of concentration of any one constituent was wide though the variability of a single constituent in any one individual was relatively limited. They further observed that “a proper balance between the lipids appears to be more sedulously protected. . . . than the absolute concentration of any one or all of the lipid components” . In healthy people the ratio of - 31 = cholesterol to lipid phosphorus was more constant than the absolute con­ centration of either of the individual fractions; free and ester cholesterol were even more closely related; however, neutral fat was comparatively independent of other blood constituents. The variations in fasting concentrations of lipid constituents among individuals was illustrated by data reported by Wilmot and Swank (1952). Eight women and six men, consuming their usual diets, were studied weekly over periods ranging from four to twelve weeks. The plasma lipid fractions and reported ranges and mean values in milligrams per 100 milliliters were as follows: phospholipids, 177 - 268 (21^); total cholesterol, 112 - 2^1 (188); free cholesterol, 1*3 - 82 (59); cholesterol esters, 68 - 169 (129); neutral fat. 37 - 157 (107); and total lipids. 477 - 722 (591). Rios- pholipids, cholesterol fractions and total fatty acids were determined; neutral fat and total lipid values were calculated. Lesser degrees of variation in concentrations of single blood lipid constituents for individual subjects were reported by Man and G-ildea (1937). In a study of changes of blood cholesterol, lipid phosphorus and fatty acids in four healthy men and six healthy women for time intervals of three months to four years, the extreme ranges of deviation from the mean for a single individual were 31 percent, 23 percent and 37 percent, respectively. The changes were not related to hemoconcentration, slight changes in weight, season of the year, or, in women, to the menstrual cycle. Further evidence of variations of serum cholesterol values was obtained from serial determinations in nineteen healthy young women during a period of 196 to 1*13 days (Wagner and Poindexter, 1952). The differences from high to low values for individual subjects ranged from 13 to 60 milli­ grams per 100 milliliters. Cyclic variations of various lipid fractions have "been observed by several workers* but the significance of the changes is questionable. Wilmot and Swank (1952) commented on a cyclic variation in neutral fat values vfoich seemed to be independent of the diet or other apparent in­ fluences; cyclic variations of phospholipids and cholesterol to lesser degrees were also observed. Changes of plasma lipids related to the menstrual cycle have been reviewed and evidence of regular cyclic variations of cholesterol esters and phospholipids have been presented by Oliver and Boyd (1953). These authors reported fluctuations of cholesterol esters from -10 to 48 percent and of phospholipids from 4^ to -5 percent of the twenty-eight day means. Other investigators have agreed that regular menstrual cycle changes occur, though the timing and degree of variations have differed. Aging as a factor affecting individual variations in lipid fraction concentrations has been studied. In 1953 Man and Peters reported on variations of serum total fatty acids, lipid phosphorus and cholesterol of seven men and nine women re-measured after ten to twenty years, the ages of the subjects having changed from an original range of 20 to h8 years to a final range of 30 to 65 years. They found no consistency in the direction of change of any of the components measured, although the con­ centrations increased more often than they decreased. These results were similar to the conclusions of Sperry and Webb (1950) » who reported that sin increase in serum cholesterol concentration was not Man obligatory concomitant of aging®*. Comparing serum concentrations in fourteen men and eight women after a thirteen to fifteen year interval, Sperry and Webb (ibid) found no change in eight men and one woman and increases of -33- 15 to 30 percent In six men and six women. £ornerup 11950) , on the other hand, reported ohservations of concentrations of cholesterol, total fat and phospholipids in the serum of ^nonnal®1 adults and observed a tendency for higher serum lipid values in females than males, in the elderly than in the young and in the pyknic than in the leptosomatic types. however? He stated, MThat elderly normal subjects present higher serum lipids than young, normal subjects may possibly be due to the presence of latent characteristic morbid alterations in pyknic subjects of this age group®1. Changes in the physical form of serum lipids with age have been observed. Serum lipoproteins of the SplO-20 class were found to be significantly higher in males from twenty to forty years of age than in females of the same age group (Gofman, et al., 1950)* More recently this same class of lipoproteins, S^.12-20 (previously included with S.^10-20), was found to increase in air force flying personnel with increasing age; interestingly, the standard deviations also increased with progressive age groups. The reported means and standard deviations for the three age groups were? 20 to 25 years, 20 4 17* 30 to 35 years, 31 4 19, and 40 to 45 years, 40 4 27 milligrams per 100 milliters of serum (Milch, et al., 1952). The relation of overweight and underweight states to blood lipid patterns has not been well defined. In 193& Hetenyi reported total blood lipid values for obese and control subjects under their usual dietary regime; total lipids averaged 890 milligrams per 100 milliliters of serum for the obese and 591 milligrams per 100 milliliters of serum for the controls, although the ranges for both groups were wide. In 1937 Man and Gildea observed that lipid values were usually higher for healthy men of *=34” pyknic build than for men of the leptoscmatic type; no similar correlation was found for women subjects. the data available stated? Peters and Van Slyke (1946) in reviewing mThe simple state of obesity, like the state of leanness, in humans appears to be associated with no abnormal patterns of serum lipids". Kornerup (1950) again, however, observed a tendency for higher serum lipid values in pyknic than in leptosomatic individuals. Man and Gildea (1937) were the first to observe that wasting diseases and malnutrition resulted in lowered cholesterol and phospholipid values; values increased as nutrition was improved. responded less regularly. Neutral fat on the other hand Keys (1953) observed that serum cholesterol was decreased in severe caloric under nutrition at all ages but was hig£i in starvation. In active weight gain serum cholesterol was reported to increase, an increase which was not dependent upon the addition of fat to the diet (Keys, 1953). No significant correlation ©f degree of obesity with serum cholesterol was found, however (Ibid). Similarly serum lipoproteins of the Sfl0-20 class have been reported to increase in active caloric overnutrition (Anderson, Lawler, Lowen and Keys, 1952), although the correlation with weight gain was not as significant as was that of the elevated cholesterol values. Walker and co-=workers (1953) have reported the effect of weight reduction and caloric balance on the serum lipo­ protein and cholesterol levels. It was observed by these investigators that serum lipid fractions tended t© fall during negative caloric balance and to rise when the balance was positive only if the Sf12-20 class of lipo­ proteins initially measured 50 milligrams per 100 milliliters of serum or more; with lower initial lipoprotein concentrations, no correlation with weight change was found. -35" Direct correlations of concentrations of several lipoprotein classes with weight have been reported. Gofman and Jones (1952) found that $f35*~100 concentrations were significantly associated with v/eight in 241 normal males; Sfl2-20 concentrations were less closely associated. In 1952 Walker and co-workers reported a progressive increase of Sfl2-20 con­ centrations with increasing degrees of overweight in one thousand subjects from thirty to sixty years of age; the increment was greater in males than in females. Measurements of total lipids in obese and control subjects early led t© postulation of increased wlipophiliaw as a metabolic characteristic of the obese (Bergman, in Borland, 1948). Lipophilia was defined as an •affinity for fat" (ibid) and the term has been used to indicate a special tendency to deposit fat as well as a resistance against the mobilization of fat from adipose tissue (Bauer, 1941). The work of Hetenyi has been cited frequently as evidence to support the concept of abnormal lipophilia in obese individuals. Hetenyi (1936) studied blood lipid concentrations in obese and normal subjects under their usual dietary regime and again after eight days of restricted diet. Total blood lipid values on usual diets averaged 890 milligrams per 100 milliliters (range, 544-1117) for the obese and 591 milligrams per 100 milliliters (range, 371- 1005) for the controls. After caloric restriction, the blood values averaged 630 milli­ grams per 100 milliliters (range, 446-802) and 605 milligrams per 100 milliliters (range, 414-897)» respectively. Heteliyi interpreted the lowering of blood lipid values in the obese as evidence of difficulty in releasing fat from adipose tissues. Blood fat values were also determined at intervals after feeding 200 milliliters ©f cream. The average maximum -36- increase of blood fat values of the controls was 8h percent above fastlog concentrations, whereas maximum increases in the obese averaged only 17 percent above fasting; wide individual variations were, however, observed. Further, the production of artificial fever in five 8 ,1normal” and seven obese subjects resulted in blood fat increases of 15 to 36 percent for the controls but no more than 11 percent in the obese. Finally, 50 milliliters of olive oil were injected subcutaneously into six obese and five control subjects and blood lipids were determined at two, four and six hours thereafter. Blood fat values increased as much as 10 to h 8 percent for the controls but only 1 to 8 percent for the obese. Wilder and Wilbur (1938) in reviewing Hetenyins experiments commented that the observations indicated that mobilization of fat from fat depots was resisted in obesity and that deposition was accelerated. They stateds MThe slightly greater than normal withdrawal of fat from the circulation postprandially could explain the delayed sense of satiety encountered in obese people and also the frequently abnormal taste for carbohydrate” . Pennington (1953a) endorsed the view of Wilder and stressed the conformity of the lipophilia theory with the current concept of the dynamic state of adipose tissue in that the lipophilia theory presumes Mactive regulation of the size of adipose deposits, rather than mere passive response of these tissues t© balance between caloric intake and output” . In contrast to these views Newburgh. (19^; 195^) has interpreted the data of Hetenyi as indicating more rapid oxidation of fat rather than as evidence supporting difficulty in the release of fat from adipese tissues. He attacked the lipophilia theory on the basis that, if it were true that the obese had an abnormal resistance to mobilization of fat, loss of -37- weight in the obese should be accompanied by increased urinary nitrogen. He stated that a variety of studies did not indicate that urinary excretion of nitrogen was increased during weight less ©f the obese and presented original data ®f three control and three obese women on restricted caloric intakes. Weight less and urinary nitrogen, were measured for successive one-week periods on unrestricted diet and diets providing 80 , 60 , 40, and 20 percent of basal energy needs, respectively. Weight losses were close to predicted losses and only negligible losses of urinary nitrogen were observed; the obese showed slightly better nitrogen balances than the control subjects. However, decreased nitrogen retentions during woight reduction of young women have been reported by Brown, Herman and Ohlson (1946), Brewer, et al. (1952) and Young (1952). Under conditions of severe restriction, Newman (Keys and Brozek, 1953) found an average total weight loss of 1.69 kilograms and a total nitrogen loss of 15 grams for tea soldiers who subsisted for nine days on 900 calorie rations. Fat loading studies in which total serum lipid concentrations were measured at intervals following fat ingestions have shown individual variations in response; in general, there was some increase, although the amplitude and time ©f peak concentration depended upon the quantity of fat ingested (Peters and Van Slyke, 1946). In a comparison of ten young 1 subjects (24.9 4 5 .21 years) and eleven older subjects (62.0 4 6.2 years), the effect of a fat meal equivalent to one gram of fat per kilogram of body weight resulted in a higher mean rise in the older group and a greater number of delayed peaks (Herstein, Wang and Adlersberg, 1953). 1 Standard deviation Distinct -38- pat ter us were not evident, however; maximum values occurred at various in­ tervals with no regularity. A composite picture of changes in individual lipid fractions following fat-loading tests is difficult to obtain due to the relatively large amount of blood required for complete analyses. The number of such studies is few. Most studies of post-prandial blood lipid responses have determined the changes in concentration of individual lipid constituents. Wilmot (1950) reported that the feeding of a fat meal of two grams of butter per kilo­ gram of body weight resulted in a rise in the neutral fat fraction which reached a peak in four to eight hours; phospholipids reached an indefinite peak in eight hours and there were inconsistent changes in the cholesterol fraction. When the amount of fat was varied from one-half to one or two grams of butterfat per kilogram, the phospholipids, neutral fat and chylomicrons increased with the amount of fat ingested; the cholesterol changes were so slight as to be of no consequence. Small and inconsistent changes in the cholesterol fraction following the feeding of varying types and amounts of fat to control subjects have been reported by others (Roay and Levy, 1929; Blotner, 1935; Corcoran and Rabinowitch, 1937; Frazer and Stewart, 1937; Oppenheimer, et al., 1943; Peters and Van Slyke, 1946) . In studies in which the responses of obese and control subjects have been compared, Oppenheimer and co-workers (1943) and R@ny and Levy (1929) found no differences between the two groups; Blotner (1935). on the other hand, reported a marked rise in blood cholesterol in his obese subjects following the feeding of 500 milliliters of 20 percent cream but no increases among his control subjects. -39- A general increase in the concentration of blood phospholipids follow­ ing fat feeding nas been reported. ^Peters and. ¥an Sj.yke, 19-^6); no comparisons of responses of obese and non-obese subjects were found. The blood fraction most commonly determined by chemical methods after fat feeding is total fatty acids because the greater part of the post­ prandial blood fat concentration has been found to be due to increased neutral fat concentrations (Peters and Van Slyke, 19^*6) . Comparisons of increases of total fatty acid concentration between obese and non-obese subjects following fat feeding have been limited. In 1929 Rony and Levy reported fat tolerances in eight control and eighteen obese subjects following the ingestion of one pint of 20 percent cream plus five hundred milliliters of water. All of the control subjects showed some rise of total fatty acid concentrations to peak concentrations at three to five hours after the feeding; increases in concentration ranged from 12 to 30 percent above fasting. On the other hand, total fatty acid concentrations in seme obese subjects remained near fasting values or decreased during the seven hour period after fat feeding. In others there were sharp increases to concentrations as high as 60 percent above fasting values. The authors commented on the "high fat tolerance" and 1 ,1low fat tolerance" as well as the “normal fat tolerance *1 observed in obese subjects. The "high fat tolerance" response of some of the obese subjects was similar to the lower total fat concentration increases in obese subjects as compared to controls reported by Hetenyi (1936). Chylomicrons, a particular physical form of blood fat, have been studied in response to fat feeding. Blood lipids, like blood glucose, represent a balance between the absorption and formation of lipids and _40- their deposition, transformation and dissimilation. Since Gage and Fish. (192^) first carried out their investigations relating chylomicrons of the blood to fat absorption, counts of the concentration of these particles have been an aid in clarifying problems of fat absorption and metabolism. A resume^ of the development of chylomicron counts has been published (Frailing and Owen,1951)* The chylomicrons are largely neutral fat with a layer of protein at the interface; they contain, however, only a relatively small fraction of the total neutral fat of the plasma (Van Eck, Peters and Man, 1952; Elkes, Frazer and Stewart, 1939; Wilmot, 1950). Details of their composition as 80 to 85 percent tri-glycerides and 15 to 20 percent sterol esters, free sterols and substances with properties of unsaturated complex hydrocarbons have been reported (Marder, Becker, Maizil and Necheles, 1952). Eighty percent of the sterol was found to resemble cholesterol with sixty-five percent in the ester form. No free lecithin, cephalin or sphingomyelin was reported. Fasting chylomicron concentrations have been found to be influenced by the time interval since the last meal and its composition (Frazer and Stewart, 1936a). Wilmot (1950) further indicated that previous diet influenced the speed at which fat was removed from the blood after a fat meal; a previous high fat diet resulted in an increased tolerance to fat. Values for chylomicron concentrations following test fat meals have shown different patterns in older as compared to younger subjects. Necheles and co-workers (Becker, Meyer and Necheles, 19^9; 1950; Marder, et al., 1952) interpreted their results as representing a definite delay in the rate of absorption and a difference in particle-size of transport of fat in aged compared to young subjects. Activity and exertion have -hi- been reported t© affect the chylomicrographs obtained in fat tolerance tests; chylomicron concentrations were increased (Marder, et al., 1952; White, Ralston and Carne, 195i)• Smoking increased and prolonged the chylomicron curve of young individuals, resulting in a marked increase and a shift of maximum concentration to the right (Marder, et al., 1952). Frazer and Stewart (1939) stated that obese subjects showed a higher maximum chylomicron concentration than did thin persons after a standard meal, although detailed data were not published; normal individuals had intermediate concentrations. Frazer and Stewart suggested that more lipolysis occurred in thin subjects and stated; “In accordance with the partition theory of fat absorption there is less lipolysis in the fat subject and therefor© more fat passes into the systemic blood to be deposited in the fat depots. In the thin person more fat passes t© the liver by the portal vein and less is stored". Considerable differences in fat tolerance, measured by chylomicron counts, in "normal" subjects were observed by Moreton (1950)* but it is noted that his classification of "normal" was only in contrast to atherosclerotic subjects. Tests at six months intervals in his study revealed that an individual tended to remain constant in his chylomicrograph pattern. Peters and Van Slyke (19^6) stated, in summarizing their discussion of studies of fat feeding, "Evidently, it Is not the amount of fat metabolized per se that determines the concentration of lipid in serum but more subtle circumstances of its metabolism which are as yet illdefined". Studies since 19^6 have not yet defined these circumstances. -42- Blood Pyruvic Acid Increased understanding of the pathways of intermediary metabolism of carbohydrates, fats and amino acids has emphasized the importance of the oxidation of pyruvic acid in the catabolism of carbohydrates and certain amine acids and in the anabolism of fatty acids. The determinations of bleed pyruvic acid concentrations and the blood lactate-pyruvate relation­ ship have been used as indications of disorder in a variety of metabolic anamolies (Bueding, Stein and Wortis, 1941; Goldsmith, 1948). Determined fasting blood pyruvic acid concentrations in control subjects have approximated 1.0 milligram per 100 milliliters of blood. Concentrations above 1.3 milligrams per 100 milliliters of blood were con­ sidered abnormal by Bueding and co-workers (1941) and Goldsmith (1948), but fasting concentrations determined in 220 individuals from sixteen to above ei^ity years of age ranged from 0.2 to 2.8 milligrams per 100 milliliters of blood (Kirk and Chieffi, 1949). In thiamine, riboflavin and niacin deficiencies, fasting blood pyruvic acid concentrations up to 2.0 milligrams per 100 milliliters were reported (Bueding,et a l ., 1941; Goldsmith, 1948) ; increased blood pyruvic acid concentrations were significantly associated with decreased blood thiamine concentrations in four subjects on thiamine restricted intakes (Hawthorne, Wu and Stoivick, 1953) . Blood pyruvic acid concentrations have not been found signifi­ cantly changed with aging (Kirk and Chieffi, 1949). Following the ingestion of glucose by control subjects, blood pyruvic acid increased to maximum concentrations at one to two hours and returned to fasting values within three to four hours (Bueding, et al., 1941; Goldsmith, 1948). Food, exercise and anoxia were the most important factors influencing the concentrations of pyruvic acid in the blood of normal persons (Frie&emann, Haugen and Kmieciak, 1945; Goldsmith, 1948). Specific studies of pyruvic acid values in human obesity and leanness were not found in the literature. Meyer and Winkler (1952) reported the behavior of pyruvic acid in different types of endocrine disturbances in which they included adiposity, loss ©f weight, diabetes and others. In nineteen of the thirty-eight cases studied, the fasting blood pyruvic acid concentration was higher than nermal and in twelve of these the concen­ tration rose in an abnormal fashion following the Ingestion of sugar. One case showed a lower fasting concentration and n© rise following the sugar ingestion. The authors found no close correlation between the type of endocrine disturbance and the slope of the curves. Pyruvic acid was observed to be depressed in obese mice ©f the hereditary obesity-diabetes syndrome strain (Guggenheim and Mayer, 1952) but t© a lesser extent than in alloxan-diabetic non-obese mice. A metabolic defect in the utilization of pyruvic acid has been postulated to occur In some individuals and by its stimulation of fatty acid synthesis to be a primary defect contributing to obesity (Stadie, i 1953a). ; Pennington, If this is true, one would expect to find higher than normal blood values in the obese similar to those found in thiamine-deficient individuals, particularly following the ingestion ©f carbohydrates. Blood Ketones Both higher anrl lower blood concentrations of ketone substances ia obese compared to control subjects have been found following various test procedures (Bretano, 1933 in Bauer, 1941; Keeney, Sherrill and MacKay, 1936). -44- Ketone concentrations increased, more slowly in obese subjects than in controls when carbohydrate was eliminated from the diet. After a carbo­ hydrate-free diet, the ingestion of ©live oil caused a greater increase in the concentration of ketone substances in the blood of obese subjects than in that of controls. Prolonged hyperventilation resulting in alkalosis raised the concentration of ketcne bodies in the blood of control subjects but had no effect on blood ketone concentrations in the obese. These results were interpreted as substantiating the existence of lower glycogen reserves and the stability of fat deposits in the obese (Bauer, 1941). Urinary Patterns of the Obese and Lean In 1951» us part of an exploratory study of individual metabolic patterns and human disease, Brown and Beerstecher (1951) investigated a group of seven overweight and ten underweight men, ranging in age from twenty to thirty-one years. These subjects showed a decided tendency to be either overweight ©r underweight and experienced great difficulty in trying to alter their weights toward normal. abnormalities according to the authors. They exhibited no other Three complete morning samples of urine were collected at intervals of three to five days; no attempt was made to control the diets of the subjects. Previous studies by this group and c©-workers had indicated that a study of urinary constituents was of value in observing individual metabolic differences; paper chroma­ tographic methods were used. Of a large group of metabolic factors which were measured, the following showed significant differences between the overweight and underweight subjects; modified creatinine coefficient and pigment to creatinine ratios were higher in the underweight group; and urinary phosphate and calcium excretions were significantly higher in the overweight group. The urinary concentrations of ketone substances following low carbo­ hydrate intakes have been lower among overweight subjects than among average weight subjects according to several investigators (DuBois, 1936; Corcoran and Eabinowitch, 1937* Bauer, i9^l) . Unpublished data from this laboratory likewise confirm the absence ©f ketonuria among overweight subjects on a low-carbohydrate reducing diet (Brewer, 1952). Similarly the absence ©f ketonuria in obese subjects on sub-maintenance diets, even when respiratory quotients were below 0.70, was observed (Lyon, Dunlop and Stewart, 1932). Average weight subjects who were fasting or who were on very low carbohydrate diets usually excreted ketone bodies when the respiratory quotient was less than 0.76 (DuBois, 1936). On the other hand Brown and Beerstecher (1953=) found that ketone concentrations in the urine were similar among overweight and underweight subjects on their usual dietary patterns. MacKay and Sherrill (1937) found that certain ©f their obese subjects excreted appreciably less ketone substances than control subjects, whereas others excreted as much and often greater amounts than average. On this basis they attempted to differentiate between the two groups of overweight subjects; they postulated that a metabolic disorder resulted in increased stability of fat deposits among the first group, whereas the latter group were diagnosed a 9 cases of simple wexogenous58 obesity. Creatinuria was more easily produced in obese than in average weight subjects by eliminating carbohydrate from the diet (Bauer, 19^1). The increased creatinuria was attributed to glycogen mobilization in the muscles and it was concluded that obese subjects had lower glycogen reserves in the liver than average weight subjects (Ibid). Summary Evidences of metabolic qualities associated with obesity or leanness which have been reported may be summarized as follows; l) basal metabolic rates of the obese or the lean showed slight or no deviations from average when based on surface area or the Mfat-free body11, but there is some question whether the Mfat-free body 15 is yet the true physiological description of all active metabolic tissue; 2) specific dynamic increments showed no consistent differences with differences in weights of subjects, but individual variations have indicated that various metabolic patterns exist, although it is uncertain whether ©r not they are related to body weight; 3 ) obese subjects had lower post-absorptive respiratory quotients but post-prandial measurements of respiratory quotients showed no con­ sistent pattern; h) glucose tolerance was decreased with obesity in middle-age, whereas increased tolerance with obesity in younger subjects, particularly in ’"active11 obesity, was reported; 5 ) fasting total lipids, cholesterol and phospholipid concentrations showed no consistent pattern in either obesity or leanness, whereas significant positive correlations of the Sfl2~20 and Sf35“lOO lipoprotein classes with weight were found; 6 ) greater lipolysis of dietary fat in thin subjects and greater post­ prandial withdrawal ©f fat from the circulation by obese subjects were indicated; 7 ) blood concentrations of ketone substances increased more slowly than average following low carbohydrate feeding in obese subjects; 8) higher modified creatinine coefficients and pigment to creatinine ratios were measured in underweights than in overweights; 9 ) higher urinary excretions of calcium and phosphorus were measured in overweights than in underweights; 10) lower than average ketone excretions in response to low carbohydrate feeding were frequently found in the obese; and ll) the significant association of a number of degenerative conditions with obesity was convincingly established. THE INVESTIGATION Experimental Procedure Experimental Plan This experiment was designed to investigate certain characteristics of the metabolic patterns of overweight, underweight and average weight women, both in the fasting state and following test meals of high fat and high carbohydrate composition. Each test meal was administered to each subject on a single day; the interval between experimental days was usually two weeks but ranged from four days to two and one-half months. Respiratory quotients and oxygen consumption were determined simultaneously with blood glucose, blood pyruvic acid, serum total lipid and serum chylomicron counts in the fasting state and at the first, third and fifth hours following the test meals. Quantitative urinalyses for total nitrogen and qualitative tests for albumin, intervals. sugar and acetone were also included at these same time In addition, blood glucose and serum chylomicron counts were determined at the one-half, second and fourth hours. Serum total cholesterol, certain classes of serum lipoproteins (5^12-20, 3^21-35* and 3^35-lGO), serum alkaline phosphatase, serum total lipid and serum chylomicron counts were determined on fasting venous blood samples obtained on the same experimental, days. Hematocrits, white blood cell counts and differential counts were determined on non-fasting capillary blood on both experimental days for each subject; in addition, red blood cell counts and hemoglobin deter­ minations were obtained for some subjects. A non-fasting resting blood -i*9- pressure measurement^ was made and fasting body temperature and resting pulse were measured each day. General medical histories, including body weight changes in adult life, menstrual history and personal and family histories of degenerative diseases, were procured for each subject. A recall diet record of the day immediately preceding each experimental day was recorded; in addition, a single random d a y ’s diet record and a diet history were obtained for each subject. Subjects Twenty-one women ranging in age from 25 to 57 years acted as subjects. The women were all active, either professionally or as homemakers; seven were married, six had had children. All were in general good health. The weights of the subjects ranged from 466 percent to -21 percent of “desirable weight *1 according to frame (Metropolitan Life Insurance Company, 1951); body builds were evaluated from anthropometric data. Measurements for each subject included height, weight, chest breadth, chest depth, breadth iliac crest, breadth great trochanter, right calf girth, right and left arm girths and right and left hand grips. inspection of body fat pads was made. In addition, an On the basis of the data, subjects were classified as having large, medium-large, medium, medium-small or small frames^. Anthropometric data for the subjects are tabulated in Table I . 1 Appreciation is expressed to Dr. Wilma Brewer for blood pressure measurements. ^ Appreciation is expressed to Dr. Wilma Brewer for the anthropometric measurements and to Dr. Margaret Ohlson for evaluation of the data. TABLE I ANTHROPOMETRIC DATA AND EVALUATED BODY BUILDS OF SUBJECTS Subject Body Build Height cm. RM SM HM HT RT MR YL Large Large Large Medium-large Medium-large Large Large 167.75 167.75 GN LP NH RW SL NS EN Medium Large Medium-large Medium Medium-small Medium-small Medium-small 165.5 157.0 RD NM YK RL RK EL NL Small Medium Medium Small Medium Small Medium 161.5 I65 .O 16*1.0 162.0 163 .5 . ,. Weight Chest Breadth Chest Depth kg. cm. cm. 112.0 30.8 23.6 106.4 31.4 24.3 22.5 25.8 20.8 25.4 25.4 27.5 21.5 20.4 21.9 82.2 82.0 76.2 76.4 77.5 69.9 63.6 67.1 60.1 25.8 26.8 26.5 18.8 53.5 54.5 57.7 24.2 23.7 19.9 19.2 17.5 16.9 16.5 26.2 16.6 167.5 I6O .5 52.5 24.5 24.6 168.0 54.8 49.6 45.0 49.7 46.0 19.2 17-3 14.7 16.3 168.0 163.5 162.5 16*+.0 173.0 165.5 15^.5 168.0 160.0 51.0 24.7 26.5 25.2 22.2 22.7 23.5 24.6 16.2 15.2 16.5 -5 2- TABLE ! co n 11 nu ed Right Calf Girth cm. Right Arm Girth Left Arm Girth Right Hand Grip Left Hand Grip cm. cm. kg. kg. 40.4 41.5 35-2 34.2 33.5 34.2 35.9 44.0 40.0 40.5 37-5 37.0 41.0 40.0 37*5 34.0 36.5 34.5 32.0 32.0 43 36 31 34.0 31.3 33.0 32.0 43 30 35 30 32 34.0 26 32.0 32.0 38 32.8 34.1 34.9 31.1 40.0 28.5 30.6 35*0 35.0 30.2 36.0 29.0 31.9 30.5 27.1 24.5 34 40 32 35 34 Iliac Crest Breadth cm. Great Trochanter Breadth cm. 36.2 35.5 32.2 31.5 31.5 31.6 32.5 30.3 29.1 31.2 27.9 24.8 27.3 29.7 27.8 30.2 27.5 29.4 38.0 32.5 35.0 26.2 28.2 31.0 27.4 23.4 27.6 32.2 28.2 31.7 35.5 33.0 30.5 31.5 34.5 33.0 26.8 31.0 28.0 32.3 35.0 30.5 26.5 25.3 24.5 24.5 25.0 24.0 23.0 25.0 24.5 24.5 25.0 24.5 22.2 23.0 24.0 22.0 22.0 22.5 22.5 22.0 28 30 23 53 25 32 22 33 32 32 20 35 22 25 32 29 32 20 48 25 32 25 28 35 30 30 26 -52- Using the Metropolitan Life Insurance Company table, “Desirable weights for women - weight in pounds according to frame "1 (1951), the desirable weight for each subject was determined and the percent deviation of the actual weight from the desirable weight was calculated. It was recognized that body density of skin fold measurements result in more exact appraisals of degrees of fatness or leanness but facilities for these measurements were not available. The subjects were grouped into three overweight class, greater than 15 percent above desirable weight; classes; average weight class, within 415 to -10 percent of desirable weight; and underweight class, more than 10 percent below desirable weight. There were seven women in each group; overweight subjects ranged from 421 to 466 percent (average, 435*5 percent), average weight subjects ranged from 413 to -10 percent (average, -0.5 percent), and underweight subjects ranged from -12 to =21 percent (average, - 15*5 percent) of desirable weight. The subjects were further classified as to whether their body weight pattern was in an “active 11 or “static11 state on the basis of the medical histories. The classifications were adapted from those of “active 11 and “static 11 obesity used by Beaudoin, Van Italli© and Mayer (1953). An “active 11 state was defined as existing when the subject was a) gaining or losing appreciable amounts of weight at the time the study was performed or b) if the obesity or leanness was of relatively recent onset regardless of whether strict dietary treatment had interrupted the progress of weight change. A “ static 11 state was defined as a long-established weight pattern. On this basis all but three subjects were determined to be “static11 in their body weight patterns; two overweight subjects and one underweight subject were adjudged to be in “active 11 states. -53- The age, height and weight data of the subjects are presented in Table II. Sixteen of the subjects were from 25 to *+5 years of age; five were between 50 a^d 57 years. Among the five women above 50 years two were in the overweight class, one in the average weight class and two in the underweight class. The mean ages of each group were similar, 39.7 4 4.7^» 36.1 4 3.3 and 36.4 4 4.2 years, respectively. three groups also were similar; The average heights of the 164.5 4 1.0, 164.8 4 1.9 and 163.4 4 2.0 centimeters for the overweight, average weight and underweight groups, respectively. The average weights in kilograms for the groups in the same order were; 87*5 ^ 5*7» 60.9 4 2.4 and 49.8 4 1.3• The differences in age and height among the three groups were not significant by analysis of variance. The differences in weight, as would be expected, were highly significant. Test Meals The test meals were designed t© provide a high proportion of either carbohydrate or fat calories from common food sources. Data on the com­ position of the test meals are presented in Table III. In the high fat test meal 70 percent of the calories were obtained from fat, 25.0 percent from carbohydrate, and 5.0 percent from protein. In the high carbohydrate meal the relative proportions of the calories were 94.5 percent from carbo­ hydrate, 0.5 percent from fat and 5.0 percent from protein. was maintained constant for both meals. The same brand of bread, orange juice, jelly and butter were used throughout. ^ Standard error of the mean* Fluid intake TABLE II THE AGES, HEIGHTS AND WEIGHTS OF SUBJECTS CLASSIFIED ACCORDING TO BODY WEIGHT Weight Class Subject Age Height cm. Overweight class BM SM HM HT RT MR YL Mean Standard error Average weight class 39.7 h.7 Mean Standard error 167.75 167.75 161.5 165,0 l6h.O 162.0 163.5 l6h *5 1.0 112.0 106 .h 82.2 82.0 466 458 431 429 76.2 76 .h 77.5 422 87.5 5.7 435.5 422 421 GN 38 165.5 69.9 413 ho 157.0 168 .O 63.6 67.1 60.1 4 6 RD NM YK RL RK EL HL 52 37 25 29 163.5 162.5 l6h.o 32 173.0 36.1 3.3 l6h.8 51 ho 167.5 160.5 51 168.0 3h 25 27 27 165.5 15^*5 36 .h h .2 163.h 2.0 1.9 168.0 160.0 Weight Status kg. LP NH RW SL HS EH Mean Standard error Underweight class 39 53 30 h5 57 29 25 Weight $ Deviation from Desirable We Ight 53.5 5h.5 57.7 4 2.5 - 0.5 - 7 - 7 -10 60.9 2 .h - 0.5 52.5 “12 51.0 5h.8 h9.8 h*5.0 h9.7 h6.0 =13 h-9.8 -15.5 1.3 -ih ■=15 =17 -17 -21 Static Static Static Active Static Static Active Static Static Static Static Static Static Static Static Static Active Static Static Static Static TABLE III COMPOSITION OF TEST MEALS 1 Calories Test Meals Fat Carbohydrate Protein gm. gm. gm. 26 . h.2 High fat test meal? White bread, toasted, 2 slices, 50 g®* 137 1.6 Butter, 38 gm. 279 30.8 Water, 100 gm. 0 0 0 0 Coffee, 1 cup^ 0 0 0 0 32 .h 26 . h.h 7°- 25.0 5.0 hl 6 Totals $ Total calories 0.2 High carbohydrate ■ 1m r - w ■ , » -m i— cjfa— — ■w-i' White bread, toasted, 2 slices, 50 gm- 137 1.6 26 . h .2 Apple jelly, 86 gm. 216 0 56 . 0.1 60 0 l h .8 0.7 0 0 Orange juice, frozen, hO gm. to 100 gm. with water Coffee, 1 cup 2 Totals $ Total calories h!3 0 0 1.6 96.9 5.0 0.5 9h.5 ^ ,0 Compositions by computation using U.S.B.A. Agriculture Handbook No. 8 (Watt and Merrill, 1950)* ^Tea was substituted for subject HM; the subject had shown a previous intolerance for coffee. Identical amounts were fed to all subjects. Although, it was recognized that carbohydrate and fat tolerance feedings were frequently based on amounts related to body weight or surface area, it was felt that there was considerable question as to a true comparative basis in working with overweight and underweight subjects. Experimental Methods Collection of Samples and Experimental Data Each woman was visited prior to her participation as an experimental subject and the general plan of procedure was explained. No attempt was made to regulate her dietary pattern prior to the experimental days except that each subject was requested to eat a dinner of low fat content and to consume no food after 7 P.M. on the day immediately preceding an experimental day. She was requested to obtain at least eight hours of sleep and rest the night before coming to the laboratory. She was asked to arise on the experimental day in sufficient time that she could be leisurely concerning necessary morning activity. It was requested that the bladder be emptied on arising and that one glass of water be drunk. The subject came to the laboratory at 7 A.M. in a post-absorptive state. As soon as the subject arrived at the laboratory, she was weighed with minimum clothing, her height measured, and then she lay down to rest for thirty to forty-five minutes. Fasting body temperature was measured just prior to the collection of the first basal sample of expired air. When the subject appeared to have relaxed completely, duplicate basal expiratory air samples of six minutes duration each were measured and - 57 - collected using a Kofranyi-Michaelis respirometer1 . Six-tenths percent aliquots of the expired air were collected into a rubber bladder and immediately at the end of the collecting period were transferred to Bailey gas-sampling bottles for storage under mercury until analyzed. Resting pulse rates and respiration rates were observed and recorded. While the subject was still reclining, a fasting venous blood sample of 25 to 30 milliliters was obtained from the anticubital vein. The blood sample was transferred to a 50 milliliter centrifuge tube, covered with parafilm and allowed to clot at room temperature for two hours. The sample was centrifuged at 2 ,0GQ revolutions per minute for one-half hour and the serum removed. The serum sample was mixed thoroughly before being sampled for total lipid, chylomicron, lipoprotein, cholesterol end alkaline phosphatase analyses. Aliquots for cholesterol and alkaline phosphata.se determinations were immediately placed in frozen storage at “5° Centigrade. Eight t© twelve milliliter serum samples for lipoprotein classes deter­ minations were placed in cold storage, 45° Centigrade. These serum samples were later packed in chipped ice in thermos containers and shipped within five days by air express to the Harvard School of Public Health for analysis of lipoprotein Sf 12-20, Sf20-35» aE-53 **6.0 lk .9 1*4.4 *4.3 k .9 5-5-53 5-19-53 **5.7 **2.8 1*4.3 13.5 4.2 4 =1*4-53 **6.6 45.6 8.2 '4-21-53 7.8 3 33 62 7.0 7.6 5 15 33 33 57 *48 MR 29 422 3-1*1-53 3-27-53 kk.O k 3 .l YL 25 421 5-22-53 6- 2-53 — **5.2 1*4.5 15.3 **.3 6.0 *4.6 2 0 0 4.1 h.h 7.2 5 35 *4 *49 55 ko 3 7 1 1 2 0 -91- TABLE VII continued Blood Fasting Pressure Body (non­ fasting) Temp. Op 128/80 98.1 98.0 128/86 9 7 .6 Resting Pulse Initial Date Last Menstrual Period Body Weight History Comments Range 190-250# in adult life; gained 10# last year. Family history of diabetes, cancer per min. 69 64 7-7-53 97.6 63 60 post­ menopause Overweight from childhood; no gain in last year. Gall bladder re­ moved; family history of cancer, heart disease. 98.0 60 97.5 65 5-5-53 6-17-53 Overweight from childhood; adul th o od, 30# loss; no gain or loss last year. Some tendency to diarrhea; no family history of degenerative disease. 106/74 97.4 98.3 60 60 4-25-53 Overweight as child; 50# gain as adult with ups and downs; steady 20# gain in last year. Diagnosed low blood pressure; no family history of degenerative disease. lhO/84 97.7 97-4 65 6l post­ menopause Steady gain for 25 years; 8# gain in last year. Slight arthritis; family history of arthritis or gout and high blood pressure. 109/68 97.3 97.5 68 200# at 20 Heart murmer one year ago; family history of heart disease, arthritis 98.4 97.6 64 57 106/74 120/87 3-3-53 years of age; lost 50#, re­ gained some; no gain last year. 75 4-20-53 145# at 18 yrs. age; up and down four times in 7 years; gained 20# last 6 mos. Takes 1 grain thyroid per day; no family history of degenerative disease. 92- TABLE VII continued Deviation. from “Desirable Weight ’ 1' 1 Subject GU 33 413 Date of Experiment 2 14-53 - 4- 3-53 LP 40 46 5- 26-53 Hematological Data HematoHemocrit globin $ gm./lOOml. 6.0 24 3 7.2 54 30 19 2 62 3 4.4 4.7 4.0 6.7 5 7 40 31 50 59 5 8-14-53 14.3 13.5 3 0 0 14.3 13.5 4.7 3.7 5.5 4.5 4 20 66 1 0 10 27 5 35 53 3 54 6 52 76 39 17 3 42.5 8-6-53 8- 12-53 43.0 40.4 RW 37 =0.5 1-14-53 2-7-53 37.3 37.9 1-22-53 2-10-53 39.3 -7 Differentials*^ L 3Sf E B 40.1 41.1 52 25 M 2 43.6 40.6 NH SL WBG 36.1 4.4 7.0 — — — — 5.4 6.6 4 4 4 1 0 -93-= TABLE VII continued Blood Pressure Fasting Body (non­ fasting) Temp. °F Resting Pulse Initial Date Last Menstrual Period Body Weight History Comments per min. 111/79 97.6 98.3 64 65 1-29-53 3-5-53 Gained 10# jr. Family history of high school to heart disease. jr. college; thyroid therapy college fr.; av. adult, 150- 160# no change last yr. 100/62 98.1 98.4 65 67 5-3-53 7-25-53 120# 6 th grade; 165# college; lost to 130#, generally 135- 108/66 97.0 97.2 73 71 post­ menopause 112/70 98.0 64 97.6 60 1-2-53 2-1=53 Takes benadryl regularly; no family history of degenerative 145#; no gain or disease, loss last year. 130# at 25 ; then gain to 145#; held 145 45# except 1941-2 (hyperthyroid) ; n© change last year. 115- 120# from 20 to 33 years; to 125# at 35; to 133# at 37 ; gain of 3-4# last year. 104/76 98.2 60 98.4 6i 1-1-53 1-29-53 As adult always in range of 116- 122#, Arrested tuber­ culosis and mild arthritis; thyroidectomy, 1942; takes antihistamines; family history of heart di seas e , tub er~ culosis, xan­ thomatosis . Takes benadryl occasionally; family history of diabetes and heart disease. Heart murmer and si. gall bladder distur. as child; no family history of degenerative disease. - 94 - TABLE VII continued Deviation from “Desirable Weight® # Subject NS EH 29 32 51 NM YK EL 40 51 34 -10 -12 -13 -14 -15 Date of Experi- Hematoment crit # Hematological Data Hemoglob in gm./lOOml. BBC 1 WBC 2 Differentials-* M L N E B # $ f 4-17-53 5-1-53 46.7 44.1 5.3 4.6 5.0 10 5.0 4 54 33 3 15.8 55 32 8 0 1 7-22-53 7-31-53 42.8 42.3 14.0 14.0 5.7 5.1 8.6 2 6.4 4 17 23 80 73 1 0 0 3-25-53 3-31-53 41.7 41.5 2-13-53 3-4-53 35 -5 37.2 7-16-53 7-20-53 42.7 42.6 5-8-53 5-15-53 15.8 1 6.8 2 27 66 5 0 6.4 7 31 57 5 0 6.8 2 8 30 53 64 35 3 5.8 4 1 0 4.9 13.1 4.7 6.6 6 13.0 4 42 35 50 60 2 1 0 0 43.3 40.0 16.0 5.0 4.2 13.8 4.8 5.2 8 22 5 33 69 57 0 3 1 2 14.0 14.0 4.5 4.2 4 45 - — 51 — 0 _ 0 47 46 44 50 3 3 0 EK 25 •17 6- 5-53 6-19-53 42.1 40.6 EL 27 -17 3-7-53 3-21-53 43.2 42.5 13.0 6.4 ---- 5.8 6.4 6 1 0 TABLE VII continued Blood Pressure lasting (non®°dy fasting) Temp. °P Resting Pulse Initial Date Last Menstrual Period Body Weight History Comments per min* 98.0 68 98.6 67 102/70 98.0 97.8 104/74 3-30-53 Adult range, 115-125#; last year lost 10#, gained 5#* No family history of degenerative disease; mother overwei^it. 80 78 7-15-53 Adult range, 125-135#; once, 1950, 1*40#; 8# loss in fall, 1952. Family history of heart disease, arthritis. 97.5 97.5 60 post­ menopause Adult range, 114-120#; lost 5# fall, 1952. Family history of heart disease. 97.4 98.0 78 72 Average 110#; 3 years ago t© 98# after ill. No family history degenerative diseases. 112/64 97-5 97.4 61 60 110/74 98.0 86 98.2 84 96/58 98.3 97.3 63 64 90/56 97.3 98.4 74 76 125/78 100/69 67 post­ menopause At 30 years, Family history of 110#; usual heart disease. adult, 130-135#; lost 15# last y r . 5-3-53 At 19, 90#; usual range, 100^ 106#; max. Liver tablet daily; some gall bladder distur.; no family history 01 de­ generative diseases. 5-30-53 At 20, 98#; usual range around 100#. N© family history of degenerative disease. At 20, 96#; av. adult range, 103-110#; no change last year. Kidney stone surgery last year; no family history of degenerative diseases. -96- TABLE VII continued Subject m Deviation from ge “Desirable Weight * Date of Export- Heioatoment crit 27 7-11-53 7-25-53 -21 38.6 37.4 Hematological Data Hemo­ globin gm./lQOml. 13.5 12.8 BBC 1 WBC 2 3.6 5.4 8.1 5.4 Differentials^ M L N E B 5 37 56 ^ Millions/cmm. 2 Thousands/cmm. 3 ^ White blood corpuscles differentiated as monocytes, lymphocytes, neutrophils, eosinophils and basophils. 2 0 TABLE VII continued Blood Pressure Fasting Body (nonfasting) Temp. °F 104/70 97.6 98.3 Resting Pulse Initial Date Last Menstrual Period Body Weight History Comments per ain. 69 73 7-5-53 100-10*4# last five years. Family history diabetes and arthritis. -98- records for the twenty-four hours preceding each experimental day. The contributions of protein, fat and carbohydrate to the total twentyfour hour calorie intakes for the single random day records are tabulated in Table VIII. Although the mean calculated twenty-four hour calorie in­ takes were 2,343 for the underweight subjects, 2,026 for the average weight subjects and 1,802 for the overweight subjects, there were wide individual differences observed among the subjects in each group. The group mean differences were not statistically significant according to analysis of variance. The percentages of the total calories contributed by protein, fat and carbohydrate were calculated, Table IX; no significant differences in the proportions of carbohydrate or fat were found among the three groups. The mean proportion of fat calories was 46.3 percent and of carbohydrate calories was 37.9 percent for the three groups; the mean proportions of protein calories were 14.5, 14.0 and 17.7 percent for the underweight, average weight and overweight groups, respectively. The limitations of single twenty-four hour recall food records in assessing diet patterns of individuals were recognized, although their us© in evaluating group patterns has been justified (Bransby, Daubney and King, 1948; Maynard, 1950? Young, et al., 1953). In groups of subjects similar in age to those in this investigation but numbering from fourteen to twenty-one in each group, Young and co-workers (1953) found little difference in the calculated total calories and total protein between estimated and measured intakes. In this study the more obvious errors introduced by varied week-end eating habits were avoided as recommended by Eppright, et a l . (1952) but seasonal variations emphasized by the studies of Thomas, et al. (195°) were unavoidably introduced since random -99- TABLE VIII CONTRIBUTIONS OF PROTEIN, FAT AND CARBOHYDRATE TO CALORIE INTAKES OF SINGLE RANDOM DAY DIET RECORDS To tftl Calories Subject Underweight! NL EL RK RL YK NM RD 2175 28X 6 2064 2302 2072 2291 2682 Mean Standard error Average weight: EN NS SL RW NH LP GN Mean Standard error Overweights YL MR RT HT HM SM EM Protein Carbohydrate gma. g ms. gms. 79 127 84 91 132 137 171 283 189 203 56 76 100 100 126 113 129 140 250 222 262 125 5.5 225 15.3 2343 111 8? 2543 2399 1746 1952 1886 1682 1972 76 74 119 147 58 76 61 76 80 86 87 302 214 197 224 118 80 105 157 176 182 71 106 207 2026 122 1204 1672 1929 1130 1654 2030 2992 8.5 3*3 66 63 75 57 96 74 123 Mean Standard error 1802 235 79 F-Value 1 (Analysis of variance) 2.55 1.22 ^F-values: Fat 8.5 P< 0.05, 3.55: P < 0.01, 6.01 9.1 61 82 117 59 79 99 154 93 12.8 2.95 17.9 103 139 155 107 153 208 295 165 25.1 2.41 -100 = Ii CM t) © > rH 3 r-j Ch © p> o CO o >■ 1 ei E-* PN ©1 VA VA * CM © On O • t -t ■it o * © u 5 CM O QO r-t vo n vr\ N• n• 4 • r-t r-4 r-t —*=t-v»o-^a Cv•. • • • N H h 4 p* CO a ■p *r^ a o <* B* CM CM va oO on oo CM o• • • O CM CM iHt o NO =♦“II —•=9 *+ t \o CM 8 o o (F-t o o♦ o 3 3 3 vy 0* P U *r"4 O > ** © ■d S3 13 <-i u-4 r-i r-4 CM VA -t OO • £ ft o r-* r-$ f -=t=1*='#=SHH CA U'•vVOft O• n -t -t A- ACA CM 0-S-t (A vA *A» (TV *A O ft o V A* a €0 © CO © f» So r—♦ at o r-S © P © +» \R. +© =» © „ -f^ tP> r-l a -« -* 4O3 O © p> « 40 4o3 o +> h O © © n—i O < a •r-i U © © © «i-s o 43 +» Vt o 02 © 3 © S*i o *4 va © O "d o & ^ | * CO P St CO # CM -101- day records were collected throughout the whole period from January through August. Limitations of calculated rather than analytical values in evaluating food intakes have been reviewed by Maynard (1950) and Hunscher and Macy (l95l)* Bransby and co-workers (1948) have emphasized the common over­ estimation of calories, carbohydrate and fat by calculated as compared to analyzed values. Thomas, et al. (1950), however, recognized a seasonal variation; analytical values for fat and protein were higher in the fall and lower in the Food habits spring than calculated estimates. of obese individuals have been studied by a variety of techniques which have yielded a variety of conclusions. Insummarizing a number of such studies, Mayer (l953b) stated; “Representative opinions expressed in the literature are as follows; obese individuals exhibit an unusually high intake of carbohydrate,,., or fat or fat-rich food, ... or normal intakes accompanied by decreased activity; and “it has been said that obese individuals eat more often, ... often eat enormous amounts of food at one sitting, ... that a larger proportion of their caloric intake is derived from evening meals and snacks, ... or that they consume most of their food at one mealM . Beaudoin and Mayer (1953) reported that obese women tended to underestimate afternoon and evening snacks and the evening meal. Using the research dietary history technique rather than the simple recall record, however, food intake patterns were revealed which were in agreement with physiologic considerations; calorie intakes of the obese women were equal to or greater than those of their controls. Proportions of carbohydrate, fat and protein in the caloric intakes were similar for both groups. Lower calorie in­ takes among obese children compared to MskinnyM children have been -102- reported, however; obese children had a mean caloric intake of 87.6 per­ cent of National Research Council recommended allowances compared to a mean intake of 103*5 percent by linear children (Peckos, 1953). In this investigation contributions of fat and carbohydrate to the total caloric intakes were similar among the three groups of subjects, although the pattern differed from that reported by Beaudoin and Mayer (1953). In this study the average contributions of fat and carbohydrate to the total daily calorie intakes were 46 percent and 38 percent, respectively; the percentage contributions reported by Beaudoin and Mayer were 37 percent by fat and 49 percent by carbohydrate. The intakes of carbohydrate and fat for the twenty-four hours pre­ ceding each experimental day were calculated because of the reported relationship of previous diet to carbohydrate and fat tolerances. data are tabulated in Table X* These No significant differences between groups were determined; marked individual variations within groups again were noted. All subjects had been requested to limit fat intake in the evening meal; it was observed that all daily fat Intakes were decreased from random day totals. The mean fat intakes in the random d a y Bs diet ar>rt in the two pre-experimental days for the underweight subjects were 125, 91 and 88 grams, respectively, for the average weight subjects, 106, 76 and 92 grams, respectively, and for the overweight subjects, 93, 64 and 76 grams, respectively; comparisons for individual subjects may be made by examining the data in Tables VIII and X. The contributions of protein, fat and carbohydrate to the calorie intakes for the three days by individual meals are tabulated in Table XXV (Appendix). -103- TABLE X TOTAL FAT AND CARBOHYDRATE INTAKES OF INDIVIDUAL SUBJECTS FOR TWENTY-FOUR HOURS PRECEDING EXPERIMENTAL DAYS 1 Calculated Twenty-four Hour Intakes ; Preceding Preceding j High Fat Test Meal High Carbohydrate Test Meal Total ! Total Total To tal Fat Fat Carbohydrate Carbohydrate gms. gms. gms. gms. .4 -*________ _ Subject Underweight t NL EL RK RL YK NM HD ! : ! I Mean Standard error Average weight* EN NS SL RW NH LP GN 66 128 71 84 93 81 112 91 8.3 ! I I : ; J Mean Standard error 133 292 136 235 227 197 189 202 22.5 77 174 201 149 171 184 115 196 76 8.8 73 81 35 66 100 105 96 122 85 74 78 66 95 88 7.1 92 119 55 91 212 240 251 167 271 232 186 223 14.1 269 268 73 115 189 199 198 178 170 35*7 92 12.8 202 20.1 105 61 44 169 83 154 199 57 41 71 83 88 131 98 50 263 151 142 133 237 63 152 \ Overweight * YL MR RT HT HM SM RM ; I 53 39 52 27 ill ^ 75 j | Mean Standard error | 64 11.4 „ j ___________ F-Value^ (Analysis of Variance) ^F-values* 1.86 252 143 27.1 1.91 P<0. 0 5 » 3*55* P^O.Ol, 6*01 76 10.8 0.62 154 28.2 2.68 -104- Energy Metabolism Energy expenditures in this investigation were evaluated in terms of total calories per hour; the energy expenditure in calories was calculated from the measured oxygen consumption and non-protein respiratory Quotient. Non-protein respiratory quotients were determined to indicate trends in the type of energy metabolism occurring. Oxygen consumption, overall respiratory quotient, non-protein respiratory quotient and calorie data are tabulated in the Appendix, Tables XXVIII to XXXI. Basal Energy Expenditures Basal energy expenditures expressed in total calories per hour of the individual subjects showed a significantly positive correlation (P< 0.01) with percent deviations from desirable weight. plotted in Figure 3. The basal data are Individual variation was apparent among all groups; energy expenditures ranged from 60 to 76 calories per hour among the over­ weight subjects, from 45 to 58 calories per hour among the average weight subjects, and from 42 to 50 calories per hour among the underweight subjects. The correlation with percent deviation from desirable weight was least evident among the underweight subjects, where differences in weight were the least. An inspection of the scatter diagram revealed a digression of data at both extremes of deviation from desirable weight. The regression coefficients were calculated therefore for data of all subjects and then omitting the data for the three subjects, RM, SM and NL, whose body weights deviated |66 percent, 458 percent and -21 percent, respectively, from desirable weight. The regression coefficients thus calculated were 0.303 and 0.4l6, respectively; the difference between -10 5* o o UO to d © t3 CJ 0) o * d to flj a .§ S3 o 4» 60 to <1) 9 4? a o ♦ p T-i* +* •d S d o & pi « t> e tt§ d 9 9 d d © o t p-4 4^ ^ © 5 5 H o ^ rq» ®oo o * 00 O ** • O Cw 0 2 • • -d03 • • m o ^ +*m o to >» d > +» to © © 04 ri +2 o to o •d (Hf & 1*4 00 o d d o © <44 d 4» <+H *6) o •H © to (5 d o © •r-l f-i W ro « © d d •H ttfl w -106- the regression coefficients was significant "by Fisher*s t-test (Snedecor, 1.9k6) , F<0. 0 5 . The predicted energy expenditures at zero percent deviation from desirable weight, however, were practically identical? 52.7 and 52.8 calories per hour. Although age Is a commonly recognized factor influencing basal metabolism, the rate of energy expenditure was not consistently decreased with age among the subjects in this study (Figure 3). The relationship of basal metabolism to body weight was examined also by a comparison of the mean values of the three groups of subjects? over­ weight, average weight and underweight. The mean total calories expended in the fasting basal state on both experimental days were significantly higher among the overweight subjects than among the average weight or underweight subjects; there were smaller and less consistent differences between the average weight and underweight subjects due to the smaller differences in body size included. The means and standard errors of the means at fasting, as well as at each hour measured following both test meals, together with the F-values for the analyses of variance and covariance, are presented in Table XI. Although some individual variation between determined basal metabolic rates on the two experimental days was observed, mean fasting values for the overweight and underweight groups showed no significant differences between the high fat and the high carbohydrate test days; the difference between the mean fasting values for the average weight group was significant, however, p<0.05. Comparisons between the two test days for the overweight and the underweight groups are valid; comparisons between the two test days for the average weight group may be influenced by the individual variations in basal calories. -107- VP Vd »» O © o © d -HI ri cC a •HI +> >> ©4 o r-C Eh ► s o -<■■o N S3 © - <3 h cjr\ t3 »A O 41 • ♦ • H UP H cp on 00 no cp no © • o H o • o © 0 © HI a i P«i » « ON H I n 3 m, vo m? -t at no of* * «• O (g cn « - * « ■ » * © © *• 4 CM CM vO CN- d Vi 0 01 r-i i -s ■p o «Mv.\0 W • 'f t •HI © Vi © > o 4 • *« •3 i ! 01 I © •H Vi , © +» O © © d CO SP Vi © > • a © •H Vi O Hi * O rl 4 r-l ; | , , CM tH • ♦ 4- CM H CD s © • © > f4 © t3 d © - *. ■*» h O rrt ^tvO *r3 CP 1 * 8 o *4*1 HhD“ t °8 * H «4p!l«+3(l*+(|-f= 1 CM CP CM OO • • • • H i CM CP H I up NO up up NO CP NO • f t m • CA N 4 iA up up up up 00 NO • O : « i 3 V< ° H © 1 o j CM OO ON CP CP Cn. • • * H H O CP up NO Q O H NO NO • • • • H •—* H H 1^=. 5— 1 j i i O O MP NO CP • • CN- NO CP * • o up vp up o ■§d' M/ ** W) P4 o P • . Pm 3 d cti v» co © © § © o v 1—w e • • © i V. 4-» * © up OO CP CP IV Jd- HI up 0O t v up * * • • H H H r—1 6 01 >» 3 5 & n 3 H vV/ ^ °. CP H 00 O n • » • • -d NO (P -4" nD N vO NO HI s 01 H • O o 43 •=*=>0“f 31*4= 0*4=-1 ■ * 3 tH 0 *o u un, 43 fj 4 H et -4 - p CM H --- ._. — -.- .i 1 •a +» to o rt Pi < +* ft H * ^ H v O Q| © * > CN-vO v p H O CM up CM OO O n • • * • H CM H H H UN C*"“ O O cm o ao up : 43 d C- H VAvO n NO CM CP, O • • » • V A r lN O N VO I S vO nO f ' ^ • * “S*i “ M~e=Q«H ! © H * HI O r i (A IA O -=J- O no * # • • CM CM CM H : HI a o p ft •H © > © •h rd • « - « * « ■ \ T \ N On H OO i r \ H CM CO N 3 *» 43 *0 V< 43 O CV -3 “ CM j3* O CM = * CM EH +» Eh v>vO . © Vi vr\ n n M) 1C, OO CO, # « « « a OO VO On CM CO On • • • • 00 VO Q CM CM CO >> trH [N H IS 0O VTi \r\ • • * • o ►—H 09 -S* CM cp oo on h • * • • fe © >• -ct • © U O V» 3 43 o * © V» v. a • -5 © O d ► •Hi • © CM up •HI CM © • ON iV O •H Vi 4* *H fJ • W) O *H V 04 *t3 •> >* h • 43 3 4 O O ja 43 »B M S’ g S V* t ! t« +> 4 i UN, I (3 wUD *d © «s*h a * CM (p V 4) (fl -108- When the basal energy expenditure data were combined for all subjects for both experimental days, the mean expenditures for the three groups were ^ 7 .0 , 52.3 and 65.1 calories per hour for the underweight, average weight and overweight groups, respectively. The analysis of variance showed highly significant differences among the groups as compared to differences among individuals within groups, P < 0.01. The mean of the overweight group was significantly higher than the mean of the average weight group, (P<0.0l); further, there was no over-lapping of individual values for basal calorie expenditures between the overweight and the average weight subjects. The difference between the means of the average and underweight groups was not significant by the method of least significant differences (Snedecor, 19h6). The estimated variance of the underweight group was unduly influenced, however, by the spread of data among the overweight subjects. The difference between the means of the average and underweight groups was significant by FisherBs t-test, P < 0.01. Energy Expenditures Following Test Meals The total calories per hour expended at rest at intervals after the test meals were consistently higher for the overweight subjects than for the average weight or underweight subjects at each hour measured. The mean hourly calorie expenditures at the first, third, and fifth hours, respectively, following the high fat test meal were 71 , 66 and 68 for the overweight subjects, 58 » 5^ and 56 for the average weight subjects and 57 , 5h and 50 for the underweight subjects; following the high carbo­ hydrate test meal, the hourly calorie expenditures were 76 , 6h and 65 for the overweight subjects, 62 , 53 and 52 for the average weight subjects -109- and 59, 51 and 50 for the underweight subjects at the first, third and fifth hours, respectively, Table XI. Individual data are presented graphically in Figure h. A significant linear variation among groups compared to the variation of individuals within groups occurred at all hours measured after both test meals; significant deviations from linearity (significant quadratic variance) occurred, however, at the first and third hours following the high fat meal and at the first and fifth hours following the hi^gi carbo­ hydrate meal, Table XI (Cochran and Cox, 1950) • Differences between average weight and underweight subjects were quantitatively less than those between overweight and average weight subjects. Differences between the overweight and average weight subjects were highly significant at every hour; differences between average weight and underweight subjects were not significant at the first and third hours following the high fat test meal and at the first, third and fifth hours following the high carbohydrate test meal as evaluated by least significant differences. The significant differences between groups at each hour were shown to be related mainly to differences in rates of fasting calorie expen­ ditures; analyses of covariance, relating each hourly calorie expenditure to the mean fasting calorie expenditure of the group, showed no signi­ ficant differences at any hour, Table XI. The F-values obtained after the high fat meal were considerably greater than those obtained after the high carbohydrate meal, however; the higher F-values following the high fat meal indicated greater group differences in calorie increments in response to fat than to carbohydrate. Figure 4. Hourly Underweight energy expenditures Subjects at intervals Average Weight on two test Subjects days. Overweight Subjects 110- -111- A comparison of the calorie response to the two test meals by the three groups of subjects was seen more clearly in a tabulation of measured calorie increments above basal. tabulated in Table XIX. The mean increments for each group are The method of plotting the hourly energy expen­ ditures above the basal energy expenditures and then deriving the total expenditure for a given time period by estimating the area under the curve was similar to that used by Strang and McClugage (1931) and Glickman, Mitchell, Lambert and Keeton (19^-8). As the number of resting energy expenditure measurements made in this investigation was limited to those at the first, third and fifth hours after completion of the test meals, the total Increments so estimated were not considered an exact measurement of specific dynamic effect of the test meals. As the measurements were comparable for all subjects, however, comparisons of the total increments measured between groups were valid. From Table XII it was apparent that the group of underweight subjects showed a greater total calorie response to both test meals than either the average weight or the overweight subjects; differences among groups were significant only following the high fat meal, however. The mean cumulative calorie increments above basal at the fifth hour for the underweight, average weight and overweight subjects were 30 , 15 and 11 calories, respectively, following the high fat test meal and 25, 20 and 17 calories, respectively* following the high carbohydrate test meal. The calorie expenditures above basal for the five hours following the high fat test meal were significantly greater among the underweight subjects than among the average weight or the overweight subjects. Differences between mean caloric responses of the average weight and overweight subjects were TABLE XII MEAN CALORIE EXPENDITURES ABOVE BASAL DURING FIVE HOUR PERIODS FOLLOWING TWO TEST MEALS Total Cumulative Calories Above Basal Following High Fat Test Meal Subject | Following High Carbohydrate Test Meal 1st Hour 3rd Hour Underweight ^.7 20.6 29.9 i 3.61 | 5.8 Average weight 2.6 10.3 15 > Overweight 2.6 Q .k 5th Hour 3rd Hour 20. k 24.9 4 4.21 j 5 .** 18.0 20.4 | 2.3 11.0 1 ^.8 5.6 16.6 17.3 4 3.6 i 5.31* Standard error of the mean 2 * P<0.05. 5th Hour ^.8 F-Value2 (Analysis of Variance) i j 1st I Hour (F-values* P<0.05„ 3.55? P<0,01, 6. 1.2? slight at any hour or for the entire five hours following both test meals. The mean increase in resting calorie expenditure following the high fat test meal was greater than that following the high carbohydrate test meal for the underweight subjects; for the average weight and overweight subjects, there were greater mean calorie expenditures following the high carbohydrate meal, the difference being the greater for the overweight subjects. Strang and McClugage (X931) observed a higher mean calorie ©xpen— diture among their underweight subjects than among their controls during six hours following a test meal which provided 26 grams of fat, 52 grams of carbohydrate and hO grams of protein. Their overweight subjects also showed a mean caloric expenditure higher than that of their average weight subjects, although not as great as that of their underweight group. The test meals in this study supplied 32 grams of fat, 26 grams of carbo­ hydrate and h grams of protein in one and 1.6 grams of fat, 97 grams of carbohydrate and 5 grams of protein in the other. Since the compositions of these meals were quite different from that in the study of Strang and McClugage, it is difficult to make exact comparisons. Further, the fact that the overweight and underweight subjects of Strang and McClugage were on reducing or up-building regimens, respectively, might have affected the metabolic responses which occurred. Reports of studies of the heat increment of carbohydrates, fats and proteins have emphasized the influence of previous diets of the subjects on the caloric responses observed. More nearly uniform responses have been demonstrated when the previous dietary pattern of the subject was controlled. In this study, however, the influence of previous diet was considered a part of the metabolic pattern of the subject. -!lh- Xndividual variations among the subjects in their caloric responses following the test meals were apparent, Figure h-, but there was a pattern of response in each group following both test meals, particularly among the average weight and underweight subjects. Total cumulative calorie increments were higher following the high carbohydrate test meal for five of the six average weight subjects for whom data were complete and were higher following the high fat test meal for five of the seven underweight subjects; average weight subject LP and underweight subjects YK and NM deviated from their respective group patterns. Among the six overweight subjects for whom data were complete, three subjects, RM, HM and RT, had higher energy responses following high carbohydrate feeding, two, HT and MR, following high fat feeding and for one, YL, there was essentially no difference. The lack of significant differences by the analyses of covariance at individual hour intervals following the test meals was a reflection of the spread of individual data, both at fasting and at the individual hour intervals measured. The estimation of total calorie increment was a better measure of the caloric effect of the test meals to the individual. Measurements of calorie expenditures at more frequent intervals would result in a more exact estimation of the true caloric response for the time measured and would also allow extrapolations to the total caloric response by the method of Glickman, et a l . (19^8). Bases of Expressions of Energy Expend!tures The data on energy expenditures in this study have been compared on the basis of total calories per hour. The basal data plotted as total calories per hour against percent deviations from desirable weight of -115- the subjects, Figure 3* incorporated, a consideration of differences of height and body build of the subjects because these were a part of the determined percent deviation from desirable weight. No other attempt to evaluate differences in the amount of active tissue was included in this factor, however. Basal calorie expenditures were calculated and considered relative to bases commonly proposed as estimates of metaboiically active tissue. The basal data were calculated as l) calories per square meter (actual weight) per hour, Z) calories per kilogram of desirable weight per hour, 3) calories per square meter (desirable weight) per hour, h) calories per kilogram (desirable wei^at)^*^ per hour and 5 ) calories per kilogram (actual weight)^ per hour and plotted against percent deviations from desirable weight in a manner identical to that in which total calories per hour were presented in Figure 3- Compared to the significant positive correlation between percent deviations from desirable weight and the data expressed in total calories per hour, the following relations were observed* the data calculated as calories per square meter (actual weight) per hour showed greater spread and no apparent digression with percent deviations from desirable weight; calculated as calories per kilogram (desirable weight) per hour, as calories per square meter (desirable weight) per hour, or as calories per kilogram (desirable weight)0 ’^ per hour, there was always a greater spread of data but there were positive relations with percent deviations from desirable weight of varying degrees; calculated as calories per kilogram (actual w e i g h t ) ^ p e r hour a wider spread of data was apparent and there was an obvious negative relation with percent deviation from desirable weight. The variations of these - 116- relations can bo observed, by comparing the fasting data presented in Figure 5- Individual data are presented in Tables XXXI and XXXII! (Appendix). The spread of data and shifts of individual data observed made it apparent that plotting “’calories per kilogram (desirable weight) per hour”1 against percent deviation from desirable weight introduced a compounded factor of height and build which became an artifact. This was also true in plotting “calories per square meter (desirable weight) per hour”1 and “calories per kilogram (desirable w e i g h t ) ^ p e r hourM against percent deviations from desirable weight; in these cases, however, the factors of height and build became increasingly compounded. Even in plotting “calories per square meter (actual weight) per hour5* against percent deviations from desirable weight there was a compounding of the factor of height. Expression of the post-prandial hourly calorie expenditure data as “calories per kilogram (desirable weight) per hour” represented an identical treatment to plotting basal data as “total calories per hour1’ against percent deviations from desirable weight; both presentations took account of height and body build and these factors only. That these were identical treatments was demonstrated by the fact that the zero hour data in calories per hour occurred in the same order as deviations from the regression line in the basal data plotted in Figure 3. Hourly calorie data calculated as “total calories per hour”1 took no account of height or body build. Comparing plotted curves of “calories per kilogram (desirable weight) per hourM to curves of “calories per hour” for the data of this study, it was observed that all shifts were oo CO o CO in o 00 CO o lO Figure 5. of mean hourly calorie to to o 00 expenditures according Cal./M2(ideal wt.)/hr Cal./Kg(ideal wt.)/hr Cal./Kg*75(ideal wt,}/hr to various methods of to A comparison expression. - Total cal./hr xx*o*x - Cal./M2(acual wt.)/hr ,. Cal./Kg*7^(actual wt/hr00cocc -117 -118- related to height in. particular hut also to differences in "build; values for the shorter subjects were adjusted upwards and the curves relatively heightened, whereas values for the taller subjects were adjusted downwards and the curves relatively leveled. There were, however, very few shifts in the relative order of the response curves of the individual subjects from that shown in Figure h. In these data, furthermore, the difference in the relative position of the mean curves was affected only slightly due to the similar mean heights of each group. Hourly increment calorie data were therefore presented as total calories per hour rather than as calories per kilogram (desirable weight) per hour, because of the greater familiarity in the use of the former. In Figure 5 the mean hourly calorie expenditures preceding and following the high carbohydrate test meal expressed as “total calories per hour*®, “calories per square meter (actual weight) per hour“, “calories per kilogram (desirable weight) per hourM , “calories per square meter (desirable weight) per hourM , “calories per kilogram (actual weight)^**^ per hour“ and “calories per kilogram (desirable w e i g h t ) ^ p e r hourM are superimposed so that the relationships relative to the various bases frequently proposed may be observed. When investigators have expressed energy expenditure data in terms of weight in kilograms 0 7*5 ^ or square meters of surface area, based either on actual or desirable weight, an attempt has been made to relate energy metabolism to some measure of metabolically active tissue more complex than that represented by height and build alone. That there is no commonly recognized basis for assessing the amount of active tissue has been indicated previously. This investigation does not present sufficient data to permit any selection of a basis of “active tissue1 "1; rather It was merely of interest to compare the use of the variously proposed bases. -119- R e spiratory Quo t lent s The mean fasting non-protein respiratory quotient was lower for the overweight subjects than for the average weight or underweight subjects; the mean quotients were 0.79, 0.83 and 0.83, respectively. This trend was similar to results reported by previous investigators (Wang, Strouse and Saunders, 1925; Hagedorn, Holten and Johansen, 1927; Strang and McClugage, 1931; Lyon, Dunlop and Stewart, 1932; and Bowen, Griffith and Sly, 193*+). The differences in the non-protein respiratory quotients among the three groups of subjects In the basal state and at intervals following both test meals were not statistically significant, Table XIII. The large variations due to individual differences within groups found at all hours in which the respiratory quotients were determined were typical of observations reported by other investigators. In addition, it was recognized that the magnitude of the standard deviation of the determined factor which was applied to expired gas analyses to correct for oxygen and carbon dioxide concentration changes which occurred during the collection of the gas samples limited the precision of these measurements in this investigation. There was a significantly negative correlation of fasting non­ protein respiratory quotients with fasting blood glucose concentrations, r « -0.512 (P< 0 .05); lower glucose concentrations were associated with higher measured respiratory quotients. On the other hand there was almost zero correlation between fasting non-protein respiratory quotients and the determined fasting serum total lipid concentrations, r = -0.027. Following the high fat test meal the mean non-protein respiratory quotients of all three groups showed an increase from fasting values in -120- © I o 3 0$ •Hi VTN4 ^CM O CN M •-=T • CM• OO• CM cn o o 5 3 • ON CNo N o• O• o-• • O r-* O so >» CJ *«1 iH > 0) TABLS XIII J-l ta -*-» o *3 -r« © © ■o *§ 03 1U © *4 +» i> •Hf 8Hr1 l>- cn> ^ 00 •=#=3«=|=»QHr 0«4*8 N • CO OO N • • • • • • o o o o o o o o O o o o o N CO ON I O N H | o• o• o• o• •Hr58Hh8«f“8*^8 t-8 VO r~i «=t°J«4=l*4=8 r\ H cvi N N N H r< CO o• On• ao• • o *H O O 0O• 00• 00• 00■ o o o o (T"l •4- cm vr\ \n g & CM Q CM 'S O On r - r \ CO ON On OO • - 6.01 © vO CM v£>NO r*8 CVl tH uH o o o o O N H H o o o o O ON CO • o o o o O ^ O O d © 0 © • +d » u © d ♦ • I o« 01 « e ca © + >S f r * i© o © oJ 82 Va © a h 4> I -» COi P* m* r * 3 • r f l w u 0 u u © © +> 65 >» •§ .* RW) ©;3 ©;3 O|j ,0 jH - h . d ,d £} S flJ *y © M -P T l ^ -i -** O 0 eg e> t h H n VA +» ■ft CO © W +» •d 5! 1 = 3 .55 ; P<0.01 * t-i C*- *H J-> • iO f t O rH (6 EH H 4 rH O n i h ■*> ov ^ V A r^ C O • •O * rH• 03• O N N H H hv o • O H • o os ^ • N o NO O • eg vd • © *p ^h rt • 1 40 O «J O ai © O rH 4> O EH — ------ 4* *HJ 4> © ► O +> *3) •H a> & © 01 +» o o *r> 'S 03 +» 'm 4 SP •H « * O CM O ON ir-H rH # CM 1-4 Ov 4 _ CO -_ rH V f\ CO vrs OO • * * • • o - o pH o o * _ CV O- ^ O -4 © O fXO 00 « rH CO VO v o CO • • • • • • O rH CMO 4 O CO • 00 © *-i * - S . rH © av c o ao 4 • • • • • VT\ CO CM i 4 CM cm CO C*- CO • • • CMo v H N • • • • H 0- V O 4 CvvO H H * 4 II * 4 “4=1* 4 1 * 4 1 * 4 II *4= ] * 4 8*4" 8 - 4 0 * 4 1 *4- (1*4* i CO -3 N 0 4 O n N H H CO CO 0 0 rH rH e 4 CM co O d eg CM ( M O - CM CM o \ h h o a ) i— 8 rH rH ao * o x: vo •v . 1 'd f v ro Cl • C3 OS rH © IT"* 0 rH v O v O 0 0 VO OO 4 © • • • • rH VT\ CM CM CM rH o o rH © SP: ;§ O V' PH 1 44 [ S CO \ 0 OV VP\ • © * • © • * n N 4 ^ CO ' O CM CM o • CM ~ M « 4 11 * 4 * 4 9 - 4 9 * 4 D* 4 (I Hr 0H r BHr 9 *4-1 *4-1 Hr 9 * 4 B VO CO rH N - O v VO 4 OO rH O v OO Cv- 0 0 0 0 rH H H V A N O CM O CO v o H OO CO CO 0 0 rH rH (« eg o o 4 4 VO, © e CM 4 CM 4 v o CO CM CO CM rH VO 4 CO ' O rH O * • • • • • • CM o o o v r*» MO CM CM H H Hf-1 4 H H * 4 51*44 * 4 0 Hr I! * 4 0 * 4 9 H rH rH CO CO co ov * 4 » - 4 0* 4 t * 4 I CM CM rH CM O s O v C^- O 0 0 0 3 v n O C S CO CO N rH rH ov ao oo oo oo © % m 4* © XI p> «M © CO CO eftcO S SP rH P» ftf Cm •a w © P» £ £ § fa O O 3 X ! XJ o - P «tj 03 X qJ o X! d £ £ fa si o XI xs o X! « d fa +* CM co 4 VT> &=♦ m |N H V. cf Ij •§ a CO CO © o a § o © X» H H p XI XJ XJ XJ <6 4 » o & • 5 XJ H-* ' d d X! ^ k q ^ XJ o +» +> S P n m J:« tH e g c o - 4 v-O p a •H « GQ O •© 4 XJ IH rH O Fh © . rH rH • VO vO O d rH © a CD •• 5 s p # « * ’ CO rH w lji> 4f^| T*^ rH t) Tj rH cS © oJ o XJ V O •CO• rH 0 - o * • 1 4VO o o rH sp «> * «■ *- « * « CM 4 • 00 ao c o ....... ------------ - EH * VO VO vr\ c o »h * CM CM • VO rH •H X9 i r'-» a ^ © « «rH 91 to rH u ti ii ■-•S 01 .a o -i4 1 CM © S 9 •d C! © p> cn vo o • o V/ 04 01 « cm © © © o x: * +3 o n u r-9 © rH *M *Ti » q d *d cC d o © •H *H vO SP • •rH d V O +> Ol «u) *r ~i » © OS W! v-» d r P> —H © +> rH © © © © © © Vt 0 © co -131- glucose concentrations of the overweight subjects were considerably below fasting values at the fifth hour; this was true also for six of the seven subjects at the fourth hour. The mean blood glucose concentrations of the overweight subjects were significantly lower than fasting concentrations at the fourth hour, P<0.05, and at the fifth hour, PcO.Ol, by Fisher* s t-test. This pattern was not observed among the average weight nor among the underweight subjects. All subjects* with the exception of overweight subject HT, showed increased blood glucose concentrations in response to the twenty-six grams of carbohydrate in the high fat test meal. Wide individual variations in response occurred within groups, particularly among the over­ weight and the underweight subjectss two underweight subjects, YK and RD, and three overweight subjects, HM* MR and Y L , had maximum blood glucose concentrations delayed beyond one-half hour; overweight subject RT showed a distinct maximum at one-half hour, which was atypical of the overweight subjects; and overweight subject HT had essentially no change in blood glucose concentrations for two hours and then a decrease. Following the high carbohydrate test meal, mean blood glucose con­ centrations at one-half hour and at the first, second, third, fourth and fifth hours for the overweight subjects were 17^. 119, 110, 8?, 80 and 8h milligrams per 100 milliliters; for the average weight subjects were 151, 115, 87, 80, 82 and 80 milligrams per 100 milliliters; and for the underweight subjects were 152 . 109, 99, 87 , 80 and 78 milligrams per 100 milliliters. Blood glucose concentrations of the one-half hour blood samples following the high carbohydrate test meal for the underweight subjects -132- ranged from 128 to 183 milligrams per 100 milliliters; four subjects had values of IhO milligrams per 100 milliliters or less. In contrast, one- half hour blood glucose concentrations of six of the seven overweight subjects ranged from l?h to 195 milligrams per 100 milliliters; one subject, RM, had a half-hour glucose concentration of only 132 milligrams per 100 milliliters of blood. The range of half-hour blood glucose con­ centrations among the average weight subjects was similar to that of the underweight group; values ranged from 126 to 173 milligrams per 100 milliliters. Blood glucose concentrations of the subjects in all groups decreased rapidly after one-half hour maximum values were reached. The mean con­ centrations, and most individual responses, showed decreases until the third hour. At the first, second and third hours, ranges of concentrations among the underweight subjects were greater than for the other two groups; at the third hour, there were wide variations in glucose concentrations among all groups. By the fourth hour variations among the individual underweight subjects had been minimized; among the overweight subjects, individual variations were more marked. By analyses of variance the mean glucose concentrations at the second hour only showed significant differences among groups; the mean blood glucose concentration of the overweight subjects was significantly higher than that of the average weight subjects, but not of the underweight subjects. This higher con= centration again was determined to be related in part to the higher fasting concentration of the overweight subjects (analysis of covariance). At the fifth hour the blood glucose concentrations of all of the overweight subjects were considerably below their fasting concentrations, and the mean concentration was significantly lower than the mean fasting concentration (P< 0.05); this decrease below fasting was particularly interesting in view of the high concentrations for six of this group at the one-half hoar period. Greater post-absorptive hypoglycemias among obese than among average weight subjects, however, have been observed previously (Ogilvie, 1935)• There was not a significant lowering by the fourth hour following the high carbohydrate test meal as was true following the high fat test meal. Again no significant lowering of the mean blood glucose concentrations of the average weight or underweight subjects below fasting concentrations occurred at any hour. It has been shown by many that carbohydrate tolerance is Influenced by previous diet. Control of previous diet thus has an important role in carbohydrate tolerance tests where diagnosis of endocrine function, for example, is the desired purpose; it is desirable in such tests to limit other factors known to increase or decrease tolerance. In a study of metabolic patterns of subjects representative of a type or group, however, dietary habits may be considered contributory to the overall metabolic picture. Therefore in this investigation, it was deemed desirable for the subjects to pursue their customary diet patterns prior to testing. It was shown by the data presented in Tables Till, IX, and X that no significant differences existed among the three groups either in the total quantity of carbohydrate consumed or in the percent contributed by carbohydrate to the total daily caloric intakes evaluated. The mean carbohydrate intakes of the overweight subjects were consistently lower, however, than those of the average weight or underweight subjects in the three calculated daily intakes. For the underweight, average weight and -13^ overweight subjects, respectively, the mean estimated carbohydrate intakes were 225, 207 and 165 grams for the random diets, 202, 170 and lh3 grams for the day preceding the first experimental day and 223, 202 and 15h grams for the day preceding the second test day. Lower carbohydrate intakes may have contributed to the tendency for the lower carbohydrate tolerances exhibited by the overweight subjects. However, there was no consistent relationship in individuals between calculated carbohydrate intakes and one-half hour blood glucose concentrations. Data from this investigation do not lend themselves to precise inter­ pretation In terms of “high1* or ®lowM carbohydrate tolerance, since pure glucose was not administered and blood sampling intervals were thirty minutes during the first hour. Furthermore, identical amounts of carbo­ hydrate, fat and protein were provided in the test meals for all subjects, although It was recognized that carbohydrate and fat tolerance feedings are frequently based on amounts related to body weight or surface area. The latter method has certain advantages, but in studying overweight and underweight subjects, there was considerable question as to the best comparative basis for feeding. High and low glucose tolerances observed among these subjects were not related to large or small body builds. The low amount of protein used in the test meal also was recognized as a factor in the type of tolerance curve obtained in these subjects in view of the studies of Addison, et al. (1953) smd Orent-Keiles and Hallman (195^). Delayed utilization of carbohydrate, or decreased tolerance, has been reported to be a common accompaniment of obesity (Newburgh, 19^2) and to be related to the duration more than to the degree of obesity (Ogilvie, 1935). Again, however, most studies of delayed utilization among overweight -135- subjects have been complicated by clinical considerations of diabetes. None of the observed delays in carbohydrate utilization among the over­ weight subjects in this study were of the diabetic-type. Further, subject RM, who had a long history of being overweight, had one of the lowest onehalf hour blood glucose concentrations of all subjects following the high carbohydrate feeding. There was an apparent tendency for increased carbohydrate tolerance among the most underweight subjects and a generally decreased tolerance among the overweight subjects. There was no evidence of increased carbo­ hydrate tolerance by the two subjects with 511activew obesity. Likewise, there were no apparent abnormal deviations from group patterns by the subjects of fifty years or more of age. The most interesting observations in blood glucose concentration changes following the test meals weres the prolonged elevation of blood glucose concentrations above fasting among the overweight subjects, particularly following the high fat test meal; and the distinct trend among the overweight subjects for glucose concen­ trations to fall below fasting concentrations at the fourth or fifth hours, while fasting concentrations were significantly higher among the overweight subjects than among the other two groups. Serum Lipid Patterns Fasting Serum Lipid Concentrations Conspicuous individual variations rather than group differences characterized the fasting values of the various serum lipid constituents measured in this investigation. cholesterol, the various This was true for total lipids, total lipoprotein fractions and for the chylomicron -136- count 6. Fasting serum total cholesterol and lipoprotein data are presented graphically in Figures 8 and 9. Fasting serum chylomicron and total lipid data are included in Figures 10 and 11 which are on pages 1^+6 and respectively. The wide range of values for all individual constituents was typical of results of studies previously reviewed. Individual data are tabulated in Tables XXXV through XXXVIII (Appendix). There were no significant differences among the means for the under­ weight, average weight or overweight subjects for any of the individual lipid constituents measured, and no constituent showed a significant correlation with the subjects’ percent deviations from desirable weight. Mean fasting values of the three groups for the various lipid fractions are tabulated in Table XV. Capillary serum total lipids showed a trend of increasing mean values froit underweight to average weight to overweight subjects of 750 , 808 and 826 milligrams per 100 milliliters of serum, respectively; this trend also was observed by Man and Gildea (1937) and Kornerup (195°) • The difference between the mean concentrations of the average weight and overweight subjects in this study was less than the difference between the values of 591 and 890 milligrams per 100 milliliters of serum which were reported by Hetenyl (1936) for his control and obese subjects, respectively. comparable. The ranges of concentrations measured were, however, quite The ranges among the subjects in this study were 505 - 990, 557 - ll66, and 699 - 106h milligrams of total lipids per 100 milliliters of serum in the underweight, average weight and overweight groups, respectively. Hetenyi reported a range of 371 - 1005 milligrams of total lipids per 100 milliliters of serum for control subjects and 5*+4 - 1117 400L O o CO Figure 8. Total Cholesterol mg,/lOO ml, u © >» o © *<“S *§ CM o lO § CVi O pH O o rH t on two o in o m women test days o r- CO XX 4» MD •rl 0> a> pH o .O CO d a © d © o t-1 © a. Fasting serum total cholesterol concentrations for twenty-one in relation to percent deviations from desirable weight. -137- to rag. $> S*. 12-20 Class: 100 ! 75 x 50 x 25_ x # X A * • • * * • 0 -20 0 S- 21-35 Class: 20 -20 0 S- 35-100 Class: 20 rag. 1001 40 60 75 50 25 ___ L 100 i> 40 60 f 75 X X 50 x ♦ 25 * *x ^ • * X X t 0 •20 Figure 9. 0 20 40 60 Percent Deviation from Desirable Weight Fasting serum lipoprotein class concentrations in relation to percent deviations from desirable weight. K rd rd 1 m Eod p *h o On • O Cn. CO • — d CM CNCM CM VO • • • O O O o CM vo vo • • co co tb •rd © » u © 'Ci cn i ...--.--- ---- --- iH o 4* “ ft *r*4 CO -49 -49 •4 0 “49 - 4 vo ON ts- vO CM oo CO CM CM 00 o o o Q P »-d ^3 R *-3 9 trH OO o • • « CO vO 0 r rd rd © *> |-d VO * ON id 0) *23 CO • VO CO • o vo ---------- CO -=fr rd CN• co CO >* rd 0 O vo Cnrd rd •45 * 4 9 * 4 0 -4 0 rd co rd VO ON O ■rd CO CO K id at -*-> ft •Hi © 5* © *3 S? o © CO rd VO • CM vo Id © > VO • NO CN- Cn• On rd *4 ! -4-0 VO CO VO CO o CO VO • CM -h- CN• CM r— 9 rd CO • NO •ft •rd © JS P « 'S p On o • • CM CO vo rd CO • CO O -4 9 -4 ) “4 * 4 1 -4 9 * 4 9*4 9 © 'P 0 rd O P | CO VO CM OO rd o rd CM CM VO CO CO -P" a} O VO CN- cs- ^ a •S CO « vO CO rd • • CM ON vc\ • CNrd CO CM rd rd -49 -4 I -4 9 -49 *4 - 4 9 *49 -4 0 -4 9 VO ON CV O VO dfr rd CM „=}■ CO dj* rd On CM O CnVO vo O- PCN- s +» P © 0 4> -rd 4» 1/1 P O o •0 fd Pa -»d P Q 3 0 © C/3 © 0 O P © > at •d •H P •fd rd rd d 4> O Ed s4 H CO rd rd P cd o • •. rd a t 3 *rJ •fd o P O •fd rd i—4 • rd a © • © 0 O P ® > dCO at 0 o 0 o O rd — u © + 3 • © H © s rd o J0 o O H O 4 » rd a W) a) +* a +> 0 o o Ed Ed T"1 *a a i 4 O 4 rd • • • H H *v a a © o o o o rd o o o '"•■— •fd ^rd^ • • M) * I 1 —O «* 0 O w'V o fd CM rd © 9 9 I CM fd VO CM CO © H O < d fn © P fd t-3 « E; • t-4 a o o rd • a1 ** o o rd 8 CM rd CO •*> b CD CO a t rd 0 rd o -rd 0 P C0 t> 4 VO VO — © © +> 4» d © s © O o o « o p © p o u o *H •rd s o >» •P J0 o o a © +> *» © i* u © 4 o © > Id © 4 o VO vO •0 r-9 n r-t flj +» •** g I o O rd O • O v/ V / I ... 0 O f t •H 0) > • vo rd © 4» O « •r* © 0 +» ft •H © > © © & _ _ i f-t © t> VO VO -i-8 4*- fe VO at CO T O •Cf 4* § os© -a -a © © VO *© O T- d £ u p © © O T* T d rt u \y ^ PM fd «VD 3 3 U © P fd -l-> © CN- vo nj © © > P © C m © X t +> «M o p« o $3 •P p CO 0 rd 05 ► < Pm © © 0 O P © > o VO •s 0 at •a ft •rd ’f t X 09 © d> o © **“» X 0 at o O «5 P +> aJ P p © > (6 Q VO 4» 3 o o P © If o •ri a o rd >> O VO Milligrams per 100 milliliters of serum for obese subjects when they were consuming their usual diets. Fasting total lipid concentrations determined in this study were higher than mean values frequently reported (Cecil. 1947; Feters and Van Slyke, 1946) and were particularly higher than total lipid values calculated from determined constituents, e. g. Wilmot and Swank (1952). Values in this study were comparable to those reported by Herzstein, Wang and Adlersberg (1953). who determined total serum lipids by the Bloor method, and to those of Gol&bloom (1952) and Kornerup (l950)» who determined total lipids by & gravimetric method. Age was an observed factor in individual variation among the subjects; lower total lipid concentrations occurred generally in younger subjects. 5he relationship of age and serum total lipid concentrations was not con­ sistent, however, conforming to previous studies reported (Herzstein, Wang and Adlersberg, 1953? Man and Peters, 1953). 5he most atypical value among all three groups of subjects was that of average weight subject NH; fasting serum total lipid concentrations were 1146 and 1166 milligrams per 100 milliliters for the two days, respectively. Variations in individuals between the two fasting concentrations of serum total lipids determined ranged from one percent to one extreme case of forty percent. Most between-day variations measured were less than ten percent (Appendix, ?able XXXV). Individual differences between fasting venous and capillary serum total lipids determined simultaneously varied up to almost twenty percent; differences among individuals of all groups were not consistently higher or lower for either venous or capillary concentrations. Mean venous capillary serum total lipids were higher, lower, and higher than capillary serum total lipids among the overweight, average weight and underweight subjects, respectively, Table XV, but none of the differences were statis­ tically significant. Further, for various reasons, the determinations of venous serum total lipids were not complete for all subjects. The lack of consistency of capillary and venous serum total lipid concentrations has been reported. Frazer and Stewart (1939b) concluded that more reliable Information was gained from capillary blood fat determinations. The cholesterol fraction, however, has been found not to differ significantly in capillary and venous serum, (Amen, 1951)• Fasting serum total cholesterols ranged from 151 to 396 milligrams per 100 milliliters; the two subjects with the highest concentrations were of the average weight group, Figure 8; GN and NH had fasting serum cholesterol concentrations greater than 300 milligrams per 100 milliliters. Two underweight, RL and RD, and two overweight subjects, HT and RT, had serum total cholesterol concentrations between 250 and 299 milligrams per 100 milliliters, Table XVI. The mean concentrations were 214, 253 and 228 milligrams per 100 milliliters of serum, respectively, for the underweight, average weight and overweight groups, differences among the groups were not significant. Age had no consistent effect on the marked individual variation within groups, although the subjects over fifty years of age tended to have higher concentrations. Although individual variations between the two days were found, the maximum range between days for an individual was 15 milligrams per 100 milliliters of serum; for the most part, between-day variations of an individual were slight compared to the variations among individuals. TABLE XVI DISTRIBUTION OF SUBJECTS ACCORDING TO FASTING SERUM LIPID FRACTION CONCENTRATIONS! Number of Subjects 300 Lipoprotein class, Sfl2-30. milligrams per 100 milliliters 0-49 50 - 79 > 80 5 0 2 4 2 0 6 0 0 (\> 5 2 0 Overweight O > Average Weight M Cholesterol, milligrams per 100 milliliters < 250 250 - 299 Underweight H Serum Lipid Fractions - > 100 100 O 50 H Lipoprotein class, 8^35“!^°* milligrams per 100 milliliters 0-49 Groupings reported by Walker, Lawry, Love and Mann (1953) The fasting venous total cholesterol concentrations showed a highly significant positive correlation with fasting venous serum total lipid determinations, r = 0.795* (R*C O.Ol). No significant correlation was found between total cholesterol and chylomicron counts. Greatest group differences among the lipoprotein concentrations were in the Sfl2-20 class. Table XV. It was regrettable that duplicate venous samples for lipoprotein determinations were not obtained for all subjects; in fact, no venous samples were obtained for one underweight, one average weight and one overweight subject. Two underweight, YK and NM, and two overweight subjects, RM and SM, had Sfl2~20 concentrations above 50 milli­ grams per 100 milliliters of serum and one underweight, YK, and one over­ weight subject RM, had Sf35-10° concentratioiB above $0 milligrams per 100 milliliters of serum, Table XVI. Chylomicron counts were determined as a measure of particulate tri­ glycerides in the serum. Alipemic blood plasma was reported as containing only a very low triglyceride concentration (Frazer, 1953), but some chylomicrons have always been observed in fasting serum (e.g. Frazer and Stewart, 1939b; Becker, et al., 1949). Venous and capillary fasting chylomicron counts for each subject on both experimental days were determined. Mean capillary serum chylomicron counts were higher in the overweight than in the average or underweight groups; the mean counts were 105 , 48, and 67 per standard dark-ground field for the overweight, average weight and underweight groups, respectively, Table XV. The group variation was not significant due to wide individual variations within each group, although the probability of the group mean differences being due to chance was only slightly greater than one in twenty. Mean venous serum chylomicron counts were lower than those of capillary serum for each group, hut again, like those of total lipids, individual deviations were not consistent in direction. The greater differences between capillary and venous serum chylomicron counts were found among the upper average and overweight subjects. Frazer and Stewart (1937) reported that capillary and venous chylomicron counts were similar when particle counts were low but that there was a marked difference when particle counts were high. Marder, et al. (1952) found venous counts five to fifteen percent higher than capillary counts in their determinations following high fat test meals Fasting chylomicron counts showed no correlations with either serum fasting total lipid concentrations or with total cholesterol concentrations this was anticipated in view of the small fraction of fasting blood lipids which is found in the form of triglycerides (Frazer, 1953). Age had no apparent effect on individual variations within groups; Becker, Meyer and Necheles (1949) likewise recorded no difference in fasting chylomicron concentrations between their young and aged subjects. In this study higher fat intakes on the day prior to an experiment were not correlated with higher chylomicron counts. However, one subject, EL, failed to follow instructions not to eat a high fat food in the evening prior to the study; the subject reported that she had eaten two doughnuts at 10 P.M. The fasting chylomicron count on the following day was decidedly higher than on the other experimental day. The lack of any significant correlation of fasting chylomicron con­ centrations with differences In degrees of adiposity was in agreement with the one report of a similar study which was found. Chylomicrographs for a normal, fat and thin subject, respectively, presented by Frazer and Stewart (1939b), showed no real difference in fasting chylomicron counts. It was of interest to note the lower fasting serum total lipids, serum cholesterol and seruzn chylomicron concentrations for subjects SM and RM, 458 and 466 percent of desirable weight, respectively, relative to values of the other overweight subjects* These women were the most overweight of the subjects in this investigation and both had long histories of being overweight. This same pattern was not true for the various serum lipo­ protein classes measured. RM consistently had high lipoprotein concen­ trations; SM had an Sfl2-20 class concentration of 4-5 and 52 on the two days but other lipoprotein class concentrations measured were low. Serum Total Lipids and Chylomicron Concentrations Following Test Meals Following the test meals, capillary serum chylomicrons and capillary serum total lipids were the only lipid constituents measured. Chylomi­ crons have been shown to be largely neutral fat and to be related to fat absorption following fat meals (e. g. Marder, et al., 1952). Chylomicro- graphs of the overweight and underweight subjects showed distinct group variations following both test meals. Figure 10, Following the high fat test meal the serum chylomicron concentrations of the underweight subjects increased more quickly, reached higher peak concentrations, and then decreased more rapidly than did those of the overweight subjects. Mean chylomicron counts per standard dark-ground field at fasting, at one-half hour and at the first, second, and fifth hours were 67 , 185. 388, 541, 466, 393 and 277 for the under­ weight subjects, 44, 75. 347, 412, 372, 35^, and 290 for the average third, fourth lh-6iO m +* o €> CO CO «*> *8) •H «> e ■a ifHl cfi o s ♦> 09 « EH © l*= CD ► CM O o LO to TP CO CO 03 CO TJ Q t—l TO >H count8 at intervals LO Chylomicron (0 +3 o © **"3 lO on two test days. o O o P. 00 CM 09 3 O w o 09 o 03 Figure 10. 09 V4 -1^7- weight subjects and 9^, 135, 303. 351* 375. 366 and 373 for the overweight subjects. Although there were individual variations within each group, the patterns of six of the underweight and six of the overweight subjects were distinct. Underweight subject, NM, showed a response typical of the overweight subjects, whereas overweight subject, MX#, showed a response typical of the underweight subjects. The average weight subjects individually tended to display patterns typical of the other two groups and generally in order of their evaluated percentage deviations from desirable weight. The chylomicrographs of NS, NH, LP and GN were typical of the overweight subjects, whereas those of EH, SL and RW were typical of the underweight subjects. Certain conspicuous individual variations in chylomicrograph patterns were observed. Variations were not the result of differences in fluid intakes however; fluid intakes were maintained constant throughout the experimental periods. One overweight subject, HM, showed an extremely high concentration of chylomicrons at the fifth hour; the serum sample was visibly milky. The only other serum sample showing the same visible milkiness was the second hour sample of underweight subject, HI*. In both of these cases the chylomicron counts were above 600 for the standard field counted. Underweight subject, RK, also responded with a second hour serum sample having a very high count; this serum sample, however, was not visibly creamy. Although no consistent attempt was made to differentiate sizes of chylomicrons, the smallness of the chylomicrons of the serum of subject R£ was in striking contrast to those of other subjects; the chylomicrons were small and numerous, but distinct. Significant differences in chylomicron concentrations among the three groups following the high fat test meal were observed at one-half hour, P < 0.05, when the mean serum chylomicron concentration of the underweight group was significantly higher than that of the average weight subjects, and at the second hour, P<0.01, when the underweight group showed a significantly higher mean serum chylomicron concentration than did the average weight and overweight groups, Table XVII. It was noted that the mean increment increase at one-half hour was marked only in the under­ weight group; the higher one-half hour mean concentration for the over­ weight group was related to the higher mean fasting concentration in this group. The highest group mean concentrations were found at the second hour for both the underweight and the average weight subjects; the highest mean concentration of the overweight group was at the third hour but there was little change in concentration from the second through the fifth hours. Fifth hour chylomicron concentrations were still well above fasting concentrations for all groups; individually this was also true. Only one subject, RW, even approached fasting concentration by the fifth hour. For individual subjects, the peaks of chylomicrographs shifted toward a later hour with increasing positive deviations from desirable weight; the pattern was not, however, consistent. Age had no apparent effect on the chylomicrographs of these subjects as was observed by Hecheles and co-workers (Becker, Mayer and Uecheles, 19^9*. 1950; Marder, et al., 1952) and by Frazer and Stewart, (1937). differences in this study were not as great, however, as those reported by these workers. The chylomicrographs determined in this study were in contrast to the results reported by Frazer and Stewart (1939b) who stated that their © o d © CvJ 5 a s rH o •tH to* © « rH CM • VO Eh § EH vo O CO •© rH © •rl ON CVf vo* B © rH to* CM « oo © to* - 15 © * rH © to* © Er* S H N M • o Ov IV Ov 00 Cv- I # • OtoV'V• toW-\•Ht o nt^wo4r\H • O >* rH © to rH to* O © © Eh < CO s H ias 1 &H o « o »-H § £ w o m © Pc t o * n © 1 E \O C O •a 1 fe "S © to* 02 © P. 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N/ N O P. vn cn- on O rH Ml H o rH m i og o cn V » o• 00• x Mi x w § rH CM v O 4 1 O CM 0 0 01 +3 © > ( ; o i ! 1 "f f l•=$*j—$*c ON O N -d oo cn O• • e • • NO O n vn O rH M Mi O rH V A4 ON vn • Ml N O • i=> CM N O co• • vn n O n M © 8 e © © £3 s +©> *& © © .d d OS ON +> o rQ o ! t < I ! 1 i 11 t w © M © e M o © rH © d *0 u © d »-H +» *» H H h © 3 3 d -4-3 0 0 © XX XX XX cS ■** «3 xX «M * +• M cn vn •a Ml W 3 & O o -S'S M M © xX xi oi T3 © cn i © © - M> vn in- -dr O U u © © d O •* a a © a o o .d xi .d S S +3 »d -d rO H O € g* +3 tj © •H © W H» CQ rH cn vn subjects © rH O O Ml H o o •» -f-! =T) -f i "3 «e s» -V* I CQ M CM weight and 6 overweight Cn vo co vn h average © 2 ^ 0) »> NO of 5 underweight, iT> N cn «+>!-*=8-H“8 co% -dcn • * •|H cm o CM O O • • Data cn N • • and 6 overweight (S -sfr weight ■a • of 6 underweight, 5 average • 3 Data CO C*- O /l O subjects cn ON - 156- lipid concentrations between groups was found at any hour after either test meal. The rise in total lipid concentrations measured following the high fat test meal were erratic and relatively slight. The underweight subjects showed the highest mean percent deviation, 420 percent, compared to 411 and 47 percents, respectively, for the overweight and average weight groups. The underweight subjects, who showed the greatest increase, also showed the most rapid decrease toward fasting concentration by the fifth hour. Following the high carbohydrate test meal, mean serum total lipid concen­ trations of the underweight subjects were below fasting at all hours measured. The third hour increase of the mean serum lipid concentration of the average weight group was influenced largely by a marked increase for subject 2iH and a lesser increase by SL. The mean of the overweight group, on the other hand, increased above fasting at the first hour, continued to rise to the third hour, then decreased between the third and the fifth hours; two subjects, SM and MR, of this group showed an early decrease and then a gradual increase to concentrations above fasting values. At each hour the mean total lipid concentrations were higher following the high carbohydrate test meal than they were following the hi^i fat test meal among the overweight subjects. The low mean serum total lipid increases of all three groups of subjects following the high fat test meal seemed inconsistent with the marked chylomicron responses observed and the generally accepted view that there is a significant rise in total serum lipids following the Ingestion of fat. InHetenyi'* study (1936), which is frequently cited, blood, fat values were reported as increasing an average of 8h percent of -157= fasting values in control subjects after a feeding of 200 milliliters of cream. Peters and Tan Slyke (19^-6) reported that fatty acids rose to an average 60 percent increase, reaching a peak in four to six hours, after eating. Frazer (1953) stated? '"After a fat-containing meal, human subjects normally show an increase of about 300 to 500 mg./lOO ml. of glycerides in the bloodw . Individual variations in the amplitudes of responses, however, have been generally recognized. Reports in the literature were examined further for some explanation of the data of this study. Responses to exogenous fat have been studied more frequently for individual blood constituents than for composite data of all lipid fractions simultaneously, mainly because of the large amount of blood which has been required for complete analyses. Individual variations in the responses of various blood fractions following fat meals were reviewed in an earlier section. The largest proportion of change was generally believed to be in triglyceride fat. Similarity of the trends of neutral fat values and of chylomicron counts have been demonstrated (Bikes, Frazer and Stewart, 1939; Cooper and iusk, 19^2; Wilmot, 1950), but the magnitude of changes were not necessarily similar. The reliability of chylomicron counts as a measure of total lipids was early questioned. Knudson and Grigg (1923) reported an association of chylomicrons with fats in the blood, but concluded that their number does not conform with the total fatty acids determined by chemical methods. MacArthur (1930) reported some correlation between total lipids and chylomicrons but stated that it was not very high. Recognizing that chylomicrons were largely neutral fat but that they represented only a small part of the total serum triglycerides, it -158- became apparent that the count of these particles per standard dark-ground field indicated at best only changes in the concentration of the tri­ glyceride fraction of the serum lipids and specifically indicated only changes in particulate triglycerides of a structural size visible in darkfield magnification. Frazer (1953) stated? (the chylomicrograph technique) . . "For many reasons . . . . is not a satisfactory method for the quantitative assessment of fat absorption10. Three studies of fat tolerance following fat feeding reported rises of total lipid concentrations of magnitudes similar to those found in this investigation. Rony and Levy (1929) reported increased fatty acid concentrations from 12 to 30 percent of fasting in his control subjects following the ingestion of one pint of 20 percent cream, while fatty acid concentrations in several obese subjects remained at fasting concentrations or even fell during the seven hour post-prandial period; Corcoran and Rabinowitch (1937) observed decreasing concentrations of total lipids as well as total fatty acids, cholesterol esters and phospholipids in some Canadian eastern arctic Eskimos following the ingestion of 200 milliliters of soya oili Herzstein, Wang and Adlersberg (1953) reported mean maximum rises above fasting of 81 and 117 milligrams of total lipids per 100 milliliters of serum for their young and old groups, respectively, following the feeding of one gram of fat per kilogram of body weight to their subjects. The mean maximum rises of total lipid concentrations in this study were 1*4-6 milligrams per 100 milliliters of serum in underweights, 66 milligrams per 100 milliliters in average weights and 69 milligrams per 100 milliliters in overweights following the intake of 32 grams of fat -159= with 26 grams of carbohydrate and. *4-.*+ grams of protein. The fat intake in this investigation was considerably less than the amounts fed in the studies cited above, but was similar to the amounts fed by Frazer and coworkers (Frazer and Stewart, 1939a). The lower increases in serum lipid concentrations observed in this study compared to those reported by Frazer and others might be influenced by the restriction of exercise which was imposed. Herzstein and co-workers (1953), who reported similar values, described their subjects as being at rest with no smoking permitted. Greater rises of serum total lipids have been associated with exercise (Peters and Tan Slyke, l9*+6) ; higher elevations of chylomicron concen­ trations also have been reported with activity (White, Ralston and G am e , 1951* Marder, et al., 1952). Further, the carbohydrate content of the test fat meal may have had a role in the degree of alimentary lipemia measured. Rony and Ching (1930) reported that the administration of glucose by mouth or parenterally inhibited alimentary lipemia in dogs; insulin was found likewise to inhibit alimentary lipemia in their animals. The authors concluded that carbohydrate metabolism played an important, if not essential role, in the regulation of blood fat concen­ trations of normal dogs during alimentary absorption of fat. Finally, it was recognized that total lipids in this study were determined on capillary serum rather than the venous serum commonly used for blood lipid determinations. Differences of blood lipid concentrations in venous and capillary serum have been reported (MacArthur, 1931; Frazer and Stewart, 1939b; Marder, et al., 1952). Arterio-venous differences of other blood constituents are well recognized (e. g. Macy, et al., 195^)- The reported altered pattern of arterio-venous glucose differences in active obesity (Mayer* 1953a) emphasized, the variations one might expect to find between capillary and venous concentrations of other constituents in over­ weight and underweight as well as in average weight individuals. That some of the difference in amplitude of rise observed among the three groups of subjects in this study might be due to differences in blood volume was considered possible. There was no apparent individual correlation with differences in body build, however. The increased concentrations of chylomicrons and/or of total lipids observed in six of the overweight and two of the average weight subjects following the high carbohydrate test meal seemed to indicate an increased rate of mobilisation of depot fat in these subjects. That fats are being continually mobilized from the depots is well established, although the mechanism of this mobilization is unknown (Frazer, 1953). Glycerides have been observed to increase in the blood in starvation; in normal people deprived of food, hyperlipemia has been found to start after about the thirty-sixth hour. The increases of fat observed were transient, usually lasting about an hour (Ibid). Remobilized fat in prolonged fasting was reported to appear as chylomicrons by Gage and Fish (192^). Attempts have been made to differentiate the particles derived from such sources as the fat depots as lipomicrons in contrast to the chylomicrons which are used to describe the particles derived from the fat laden chyle (Elkes, Frazer and Stewart, 1939). Actually, however, the two are indistinguishable microscopically, a fact which was emphasized by Gage and Fish in 192^. These periodic Mfat crisesw , or transient lipemic outbursts have shown chylomicron rises from a base of 10 to concentrations of about $00 particles per standard field (Frazer, 19^-8). Frazer postulated that they were caused "by nervous factors, hormones and possibly by varying metabolic demands. Previous reports of increased chylomicron concentrations in the serum following high carbohydrate feeding were not found. Rather, Gage and Pish (l92h) stated that wthe feeding of neither protein nor carbohydrate nor any combination of them resulted in chylomicron increases in healthy men and animals"*. Fraser and Stewart (1937) likewise reported no marked changes la chylomicron counts following the feeding of a non-fatty break­ fast. A slight initial rise within ten minutes was seen which the authors ascribed to a stimulus to intestinal movement which caused a consequent passage of chyle, laden with fat from the previous meal, into the blood stream. Minor intermittent diurnal maxima and minima in chylomicron concentrations, particularly during the night, have been re­ ported (Bohm, Gernandt and Holmgren, 19^1). Reports of previous studies in which total lipids were measured following non-fat feeding were not found. That marked and sustained increases of total lipid concentrations occurred in five of the overweight subjects and to the same degree in only one average weight subject, NH, and in none of the underweight subjects would indicate a metabolic pattern which appears t© be associated with obesity. Further, the two other overweight subjects after an initial fall were both showing rising total lipid concentrations above fasting values from the third to the fifth hours. This same pattern was observed in only one other subject, YK, an underweight subject, but the amplitude of rise in this subject was much less. - 162- Blood Pyruvic Acid Concentrations Fasting Concentrations Fasting blood pyruvic acid concentrations were significantly different among the three groups of subjects, P<0.01; vealed a linear response among the groups. the analysis of variance re­ The mean fasting concentrations for the underweight, average weight and overweight subjects were, respectively, O. 85 , 1.02 and 1.22 milligrams per 100 milliliters of blood. The mean fasting pyruvic acid concentrations of the overweight and under­ weight groups were not significantly different from that of the average weight group but the difference between the mean values of the overweight and the underweight groups was highly significant (?<0.0l). The fasting blood pyruvic acid concentrations were not significantly correlated with percent deviations from desirable weight of the subjects, however. Individual variations were marked among the overweight and under­ weight subjects; the average weight subjects showed less individual variation. Four jof the seven overweight subjects had fasting blood pyruvic acid concentrations greater than 1.3 milligrams per 100 milli­ liters of blood on at least one of the two experimental days; the concen­ trations for both days were above that value for one subject, MR. Concentrations above 1.3 milligrams per 100 milliliters of blood have been, considered abnormal (Bueding, Stein and Vfortis, 1941; Goldsmith, 1948), but many of the 220 subjects of Kirk and Chieffi (1949) had fasting pyruvic acid concentrations eQual to or greater than those of these ' subjects. One underweight subject, HL, had particularly low fasting blood pyruvic acid concentrations, but again they were well within ranges reported (ibid). Underweight subject YK had fasting blood pyruvic acid concentrations high for her group and overweight subjects RM and HM had concentrations low for their group on both experimental days. Individual variations between the two experimental days were quite high among all three groups of subjects, but variations were particularly high among the overweight subjects. A significant positive correlation between fasting blood pyruvic acid concentrations and fasting blood glucose concentrations was found r s 0.526 (P< 0.05), although the relationship was skewed. Fasting pyruvic acid values were concentrated between 0.90 and 1.00 milligrams per 100 milliliters of blood for a wide range of fasting glucose concentrations, but high glucose concentrations were accompanied by high pyruvic acid concentrations. There was no significant correlation of fasting blood pyruvic acid concentrations with fasting non-protein respiratory quotients, although fasting glucose concentrations and fasting non-protein respiratory quotients were found to have a significantly negative correlation. The differences in fasting blood pyruvic acid concentrations among the overweight, average waight and underweight subjects in this study were indicative of a possible difference in metabolic pattern. The overweight and underweight subjects of Meyer and Winkler (1952) displayed similar tendencies toward higher and lower fasting blood pyruvic acid concen­ trations, respectively; the mean fasting blood pyruvic acid concentrations for their two groups were, overweights, 1.08, and underweights, 0.89 milligrams per 100 milliliters. Wide individual variations occurred, however; their subjects were all patients with a variety of diagnosed metabolic disorders, classed by the authors as ""endocrine disorders’". -164- Following Test Meals The mean, blood pyruvic acid concentrations at the various time inter­ vals measured following both test meals, together with the F-values for the analyses of variance and covariance, are presented in Table XX. No significant differences among the group mean concentrations occurred at any hour following either test meal; at the first hour following the high carbohydrate test meal there was a significant difference among the groups, however, in change from fasting concentration (F-value of covariance was 4.12, P<0.05) . Individual data are presented graphically in Figure 12 and Table XXXIX (Appendix). Following the high fat test meal, blood pyruvic acid concentrations at the first, third, and fifth hours, respectively, in milligrams per 100 milliliters were* 1.27> 1.06 and 1.17 for the overweight subjects; 1.00, 0.94 and 1.05 f o r the average weight subjects; and 1.11, 0.86 and 0.91 for the underweight subjects. In general, there was little change in blood pyruvic acid concentrations from hour to hour although individual variations occurred among all groups. Two of the underweight, KL and ED, none of the average weight and one of the overweight subjects, SM» had increases at the first hour of approximately 0.50 milligrams per 100 milliliters; by contrast, overweight subject MR had definite decreases from fasting value at the first and third hours and underweight subject RK showed no change from fasting at any hour. At the third hour six of the overweight subjects, five of the average weight and only one of the underweight subjects, YK, had blood pyruvic acid concentrations below fasting values. among all groups. Fifth hour concentrations were similar to fasting values -I 65- © O f* O :H <4 cC EH MEAK BLOOD PYRUVIC ACID CONCENTRATIONS AT INTERVALS OK TWO TEST DAYS (> i-9 o 0 4> CM } © © si! o H I 0 <41 c4 CM CM OO H O CM « -4 vo • o VT\ o F-. *>CJ • o meal, ; # csl IV CM O CM O O test vo r- 43 CM and P<0.01, respectivelyt high fat test meal, fasting, 0.23 and 0.33 W -H ;*h r1 f4 e l*»;< ’>■ VO CM• CM vO O GO 00 OB * HI © 4> 3 •a N• H• vr•\ N• VO CM H H n 4 - 00 rt • fr8 •H O vo o r>, o vo r w o o\ O • • • -4" Hi O CM CM .=*• \r% CM r~i• H• HI• H• •a O O H H -+I-+I Q CS- VO IV CM CM • <5 • O H * • VP\ CO as • » • • O H O O © 4 Co cC H I © O • a O © Xi s / 43 PM O • H• H• O• O O O O -ft-II-ft*Hhl=H CM CD• 4 • 00• O n• O o HI o o U O u H a « H w © ° N W t*> ”3 5 ► © d © 43 <4 a +» 43 &« © o nW) hS3 hP d h © 43 0 o o o +3 4* d © +3 ,cj V( (3 h 01 h rl 4J i?^ •a» W W 43 « S I § §§ s o •* a o © o P H *rl ^ ^ *4 <443 (3 « » 4> Tj 4 o a c6 © u ■*» pt, H r"l -h • •» 0 • 0 •a H OS « « +> CO H V PM W * CM differences for P<0.05 0.37; high carbohydrate !» CJ HI i*H Qj aJ Least significant fasting, 0.27 and 1O Figure 12. Subjects Blood pyruvic Underweight acid concentrations Average Overweight on tiro test days. Subjects at intervals Weight Subjects -167“ Following the high carbohydrate test meal, the mean blood pyruvic acid concentrations of the three groups showed an increase at the first hour, a decrease toward fasting values or below at the third hour and a slight increase at the fifth hour. From fasting mean pyruvic acid concentrations of 0.86, 1.00 and 1.2b- milligrams per 100 milliliters of blood in the underweight, average weight and overweight groups, respectively, the mean concentrations at the intervals measured were? and 1.55» first hour, 1.41, 1.92 third hour, 0.88, 0.87 and 1.09 and fifth hour, 0.92, 0.98 and 1.13 milligrams per 100 milliliters of blood. The differences in elevation from fasting concentrations among the three groups were significant at the first hour; the increase in mean concentration from fasting for the average weight group was significantly higher than was that of the overweight group, though not higher than that of the underweight group (Fisher"s t-test). There were three overweight subjects, Y L , HM and EM, and one average weight subject, SL, who displayed no increase in blood pyruvic acid concentration in response to the high carbohydrate test meal. It is difficult to evaluate the significance of the measured blood pyruvic acid concentrations in response to the test meals. The minor changes following the high fat test meal were anticipated. The marked increases in pyruvic acid concentrations, ranging from 0.76 to 1.81 milligrams per 100 milliliters of blood, among five of the seven average weight subjects in response to the ingestion of ninety-seven grams of carbohydrate were unexpected in view of maximum rises of 0.14 to 0.93 milligrams per 100 milliliters of blood reported by Bueding, Stein and Wortis (l94l) following similar carbohydrate intakes; Bueding and coworkers fed 1.75 grams of glucose per kilogram of body weight to their -1.68= subjects. Goldsmith (1948) reported a mean maximum rise of 0.40 milli­ grams per 100 milliliters of blood in normal subjects following glucose administration. Among the twenty-four underweight and overweight patients of Meyer and Winkler (1953), the maximum increase in blood pyruvic acid concentration reported in response to a one-hundred gram test dose of glucose was 1.00 milligrams per 100 milliliters; one underweight and three overweight subjects responded with increased concentrations greater than 0.50 milligrams per 100 milliliters; two underweight and five overweight subjects showed depressed concentrations. The responses of the under­ weight and overweight subjects in this investigation were quite similar to those reported by Meyer and Winkler (1952)» except that all of the underweight subjects in this study showed some increase in blood pyruvic acid concentration at the first hour. It is possible that elevations of blood pyruvic acid concentrations occurred at some time other than the hours measured in this investigation. The data of Meyer and Winkler (1952) in which measurements were made at one-half, one, one and one-half and two hours after glucose ingestion indicated irregularities in the hour of peak concentrations. Among the underweight subjects, peak concentrations occurred at fasting for one, at one-half hour for two, at the first hour for four and at one and onehalf hours for two of the subjects; among the overweight subjects the concentrations were highest at fasting for five, at one-half hour for one, at the first hour for seven and at one and one-half hours for two of the subjects. The greatest proportion of peak concentrations for all subjects occurred at the first hour. Smith (1950) observed maximum blood pyruvic acid concentrations at thirty to fifty minutes after intravenous injections of glucose. -169“ A metabolic defect in the utilization of pyruvic acid by the obese has been postulated (Stadie* 1940; Pennington, 1953a-)» whereas depressed pyruvic acid responses have been reported for obese mice of the hereditary obesity-diabetes syndrome strain (Guggenheim and Mayer, 1952). Five of the fifteen overweight subjects of Meyer and Winkler (1952) had decreases from fasting values of blood pyruvic acid following high carbohydrate feeding. Three of the seven overweight subjects in this study exhibited a depressed blood pyruvic acid response to high carbohydrate feeding. No high elevations of blood pyruvic acid concentrations occurred among the overweight subjects following high carbohydrate feeding. Fasting blood pyruvic acid concentrations among the overweight subjects were higher, however, than those of the average weight subjects and significantly higher than those of the underweight subjects. Fasting Serum Alkaline Phosphatase Concentrations Phosphatase enzymes are distributed widely among various tissues. Serum alkaline phosphatase concentrations are elevated from average ranges in a number of diseases of osseous origin and in several nonosseous conditions, particularly in certain liver disorders (Hawk, Oser and Summerson, 1947; Goldsmith, 1950). Bessey (Goldsmith, 1950) has suggested that determinations of serum alkaline phosphatase might be as useful a tool as hemoglobin determinations in assessing general nutritional status. Fasting venous serum alkaline phosphatase concentrations were determined for the subjects in this investigation as a possible indication of metabolic stability or instability. -170- Fasting serum alkaline phosphatase concentrations for all subjects are presented in Figure 13. There was no consistent relationship between fasting serum alkaline phosphatase concentrations and the percent deviations from desirable weight of the subjects. The mean concentrations of serum alkaline phosphatase for the underweight, average weight and overweight subjects were 1.25 4 0.11^, 1.25 4 0.13 and 1.45 4 0.08 nitrophenol units, respectively. Although the mean concentration of the overweight group was higher than those of the average weight or underweight subjects, the differences among the groups were not statistically significant. Age was not a factor of individual differences. Three of the forty-two serum alkaline phosphatase determinations were made on capillary rather than venous serum. indicated in Figure 13- These individual values are An inconsistent difference between venous and capillary serum alkaline phosphatase concentrations has been reported (Macy, et a l ., 195*0 • The mean fasting serum alkaline phosphatase values of the three groups of subjects were similar to the median value of 1.36 nitrophenol units, using the same method of Bessey, Lowry and Brock (1946), reported by Macy and co-workers (1954) for four hundred and one non-pregnant, white subjects. The range of values of the individual subjects in this study also was well within the tenth to ninetieth percentile range of 0.90 to 1.96 nitrophenol units reported by Macj, et al. (1954) as a standard for normality. No differences in metabolic pattern among the overweight, average weight or underweight subjects in this study were revealed by the deter­ minations of serum alkaline phosphatase concentrations. Standard error of the mean. w u rt tj © o >» o O tv r-< O .o & +> cd O r-4 © «H O tD •§ & CO o X O O m p> ■a •r* 4> I* O ^ to cd (h *r-« CO © B o Sh fl o •H cd o *h iH > © rt © o O f-1 © (X. o iH 13. I CO Figure p f* fS X=> O c ©t si p. o *« +» Fasting venous serun alkaline phosphatase concentrations fro twenty-one women on two test days in relation to percent deviations froa desirable weight. -1.71- $ # 03 O CO ■ i-H O cv> 0 r— t O c£> • O O -172- Urinary Patterns Urinary Albumin, Sugar and Acetone Bodies The results of the qualitative determinations for albumin, sugar and acetone bodies in fasting urine samples and complete collections for the first hour period, the first to third hour period and the third to fifth hour period following both test meals are tabulated in Table FXI. data revealed no group patterns. for urinary albumin. The There were no positive determinations There were two positive urinary sugar tests; both positive tests were in the first hour collection following the high carbo­ hydrate test meal and both were for underweight subjects. subjects, NM, also showed a trace at the third hour. One of these Acetone bodies were not determined for the entire series of experimental days. Among the subjects for whom this test was determined, only one showed a sufficient excretion of acetone substances for a positive test. Underweight subject, SL, excreted acetone substances in the fifth hour sample following both test meals; marked depressions of non-protein respiratory quotients occurred concurrently. In response to the high fat test meal, the non- protein respiratory quotient was depressed from a fasting value of 0.83 to 0.71 by the fifth hour; in response to the high carbohydrate test meal, the non-protein respiratory quotient was depressed from 0.76 to O .65 by the fifth hour, Figure 8 . Traces of acetone excretions were found for one overweight and one other underweight subject, YL and BD, respectively, following the high fat test meal. Under the conditions of this study, there was no evidence of lower urinary concentrations of ketone sub­ stances following low carbohydrate intakes among overweight than among average weight subjects as has been reported (BuBois, 1936; Bauer, X9^l). “173- TABLE XXI QUALITATIVE TESTS FOR UHINARY ALBUMIN, SUGAR AND ACETONE BODIES AT INTERVALS ON TWO TEST DAYS Sub­ ject Sugar Albutain__ ____ ___ _____ __ 1 r Test Meal? High 1 Test Meali High Eat Test Meal i High Eat Carbohydrate East­ Hours Hours FastHours East­ 3rd 5th 3rd 5 th ing ing 1st 3rd 5th 1st ing 1st RM SM HM HT RT MR YL Nog, Nog. Neg. Neg. Neg. Neg, Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. |Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. GN IP NE RW SL NS EN Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg, Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. !Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. RD NM YK RL RE EL NL Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. iNeg. Neg. !Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. - 17 k 'CABLE XXI continued Sugar Test Meals High Carbohydrate 'Elours East­ 3rd 5th ing 1st Acetone Bodies Test Meals High Tat Fast­ ing 1st Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. I Neg. 1 Neg. : Neg. ! Neg. j Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. j Neg. i Neg. Neg.! Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. SI. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg.j Neg. Neg. Neg.! Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Hours 3rd 5 tii Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. t Meal; Hi^i rbohydrate Fast— Hours 3rd 5th ing 1st ! Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg.! Neg. Neg.; Neg. Neg.j Neg. Neg. Neg. Neg. Neg. Neg. Neg. SI. j Neg. ) Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. SI. Neg. Neg. Neg. SI. ! Neg. Neg. Neg. 4 . Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. Neg. 4 Neg. Neg. Neg. — => -175- Vr inary K itrogep Sxcretioaq Marked individual variation characterized the fasting hourly urinary nitrogen excretions among these subjects; this variation existed both within groups and between days for the same individual. The mean fasting hourly urinary excretions, including data of both experimental days, were 350* ^ d 550 milligrams for the underweight, average weight and over­ weight groups, respectively. Because of the individual variations, the differences among groups were not statistically significant. The mean hourly fasting urinary nitrogen excretions and the ex­ cretions for the intervals from fasting to the first hour, first to third hours and third -to fifth hours following each test meal are presented in Table XXXI. Figure lh. The individual data by groups are presented graphically in Individual variations in response in each weight group were apparent. Following the high fat test meal, the mean hourly urinary nitrogen excretions were 3 5 0 , 311 and 258 milligrams for the underweight subjects, h37» ^22 and 3 ^ milligrams for the average weight subjects and 395. ^75 and 351 milligrams for the overweight subjects. The mean hourly nitrogen excretions of the underweight subjects showed little change from fasting values during the first hour and then a small decrease during the next two collection periods; average weight subjects showed a rather consistent decrease in hourly excretions from fasting values during all collection periods, but a more marked decrease from the third to the fifth hours; the overweight subjects showed an initial marked decrease from fasting values, an increase during the subsequent two hour period and a decrease again during the final two hour period. Differences among groups were 176- © ■P © © 00 fa O ft CM © • • « © CM a in • ft o -4 § -s 4-i ] (y fa ft © - © 00 ft COi «S ft d •r-4 © © v* fa «s o a i (fa CM m v o * © VO VO © a © cm H * Cn d >» r-i a rt o CM r\ • +» OO O © a ft • n X! -4 U N O CM CM OO (A -Hi o c°\ -4 .4 cn- ^ © © * * • vxn « © • ON On >* ^ ft o © xi > ft ft * © .4 vr\ cvco vr\ tH • i n © vO O © « o +» © V Ai 2 s «■#■a N O CM N VA ir\ r\ 4 1 n ► c n 4 4 o -O n CO m as o ft w ** ft 3 ■a •H e-« <0 ft o «> T» •§ S££ e a © fa © ft 4cm «©fl h NO 'O «> ft *4 xi •a •H © fa -h h O- n 14 © ft n ca n VO 4 m IP Vi O © « i>* H (0 rt ft t © ft 0 Hi n CA N o (d ft V/ O ft (fa fa © d cti ft d © ft ft ft o a o fa © • £ fa m Vi xi ft S « -4 © vr> O ft vO © © a Vi Vi v/ d g2 ft o S ft ft r > 00 A* Vi O « £ £ r~i ft h O ft 00 »A H in n ^ to © CO no 4 O un cm CM ft ft1a~t=jft*?ft3 CO ON CTN -4 v n © 4 on cn ■=§=■I] «■$“!! Hr fl C*% ol -©i CM N O N 4 tv- >n © £> O -4 ft CM CM CM ft 1ft®Oft”0ft1( 1 -4 ft w\ O g O Oi vr\ -4 rv C\ VA cn -4 -4 -4 c*n fa CO in -4 v o O vrn O X © fa © o o 8 X! A a +» © © a t $ <*> vrv © © o ft ft 4* X3 © © ft ft *M C0 © fa ft C*> A* a +r*f w cn (TV m © fa h 3 B © o © ft XJ xi a ft c*\ fa 3 i cni vr\ M & xj © *® a o■ © © X> ft ft xJ ft ft fa rt ft dJ © to ft’ ft ft o a bj ©t © fa i ft rv ft « ft © W ft ■S fa o fa fa © ft O o o X3 X3 vr\ ft o d ft ft • tio fa fa rv c a o v/ © © © .► Vl +» ft (fa a © ft ft © « ft CO ft ft ift »fa © cm m 14. urinary Subjects Hourly Underweight Figure «> u M xi nitrogen Subjects at intervals Weight excretions Average on two test days. Overweight Subjects -178- statistically significant for the first to third hour collection, P< 0 .05 ; the mean hourly nitrogen excretion of the underwei^it group was signi­ ficantly less than those of the average or the overweight groups. The mean total nitrogen excretions for the five hours following the high fat test meal were? overweight subjects, 2,046 milligrams, average weight subjects, 1,971 milligrams and underweight subjects, 1,486 milligrams. The mean nitrogen excretion of the underweight subjects was significantly lower than those of the other two groups, Table XXIIt. Following the high carbohydrate test meal, the mean hourly nitrogen excretions were 389, 349 and 294 milligrams for the underweight subjects, 404, 431 and 395 milligrams for the average weight subjects and 510* 462 and 387 milligrams for the overweight subjects. Again the patterns of the mean values of the three groups were dissimilar? the underweight group showed an initial rise during the first hour with a gradual decrease in mean hourly excretion during the next two two-hour collection periods; the average weight group showed an increase from fasting in the initial hour collection and then small changes in hourly excretions during the next two two-hour periods; the overweight group showed a consistent decrease from fasting value for each period measured but individual variations within the group were marked. There were significant group differences in hourly mean nitrogen excretions during each collection period following the high carbohydrate test meal, P < 0 . 0 1 (Table XXII) . During the first hour the overweight group excreted significantly more nitrogen than the average or underweight groups, P<0.05; to the third hours, from the first the underweight group excreted significantly less nitrogen than the average or overweight groups, P<0.05; during the last -179- TABLE XXIII TOTAL URINARY NITROGEN' EXCRETIONS DURING FIVE HOURS FOLLOWING TWO TEST MEALS Subjects Experimental Period Following high fat test meal^ Underweight Average Weight mg. mg. i486 + 771 F Value^ Analysis of Variance Total Overweight mg. 1973 4 1801 2046 4 I421 4.72* t Following high carbohydrate test meal^ 1675 4 77 2056 4 76 2208 4 152 6.49** Standard error of the mean 2 * - P < 0 . 0 5 ; ** ~ P< 0.01 (F-values* P<0.05, 3.55'* P<0.01, 6.01) ^ Least significant differences for P < 0 . 0 5 and P<0.01, respectivelys following high fat test meal, 431 and 605 ; following high carbohydrate test meal, 332 and *+65 -180- period the underweight group again excreted significantly less nitrogen than the average or the overweight groups, P< 0.01. The mean total amounts of nitrogen excreted during the five hour period following the high carbohydrate test meal were: overwei^it group, 2,208 milligrams; average weight group, 2,056 milligrams; and underweight group, 1,675 milli­ grams. The mean nitrogen excretions of each group were similar to those for the same period following the high fat test meal, although they were higher in each case, Table XXIII. The higher, though not significantly higher, mean fasting hourly urinary nitrogen excretions among the overweight compared to the under­ weight subjects in this study perhaps was influenced by the overweight subjects having a larger musculature. The anthropometric data presented in Table I led to the evaluation of generally larger frames among the overweight subjects. Obese have been reported to have large musculatures (Meikel John, 1953) I the data of Keys and Brozek (1953) would support an increase of cellular mass with increasing adiposity. Age had no consistent effect on fasting urinary nitrogen among the subjects in this study. No consistent relationship could be discerned between the protein intake of the twenty-four hours preceding experimental collections and fasting hourly urinary nitrogen excretions; there was no apparent relationship between the protein intake and hourly urinary nitrogen excretion among individuals or between the two experimental days for single individuals. There was less individual variability in urinary nitrogen excretions among the subjects after the test meals, particularly among the average weight and underweight subjects. Both test meals, likewise, had the effect of decreasing hourly urinary nitrogen excretions among all groups, even though the protein content of both meals was less than five grams. These data indicated a better protein-sparing effect by the high fat test meal, in which calories were 70 percent from fat, 25.0 percent from carbohydrates and 5.0 percent from protein, than by the high carbohydrate test meal, in which calories were 0.5 percent from fat, 94.5 percent from carbohydrate and 5.0 percent from protein. Five of the overweight, three of the average weight and five of the underweight subjects had lower five hour urinary nitrogen excretions following the high fat test meal than following the high carbohydrate test meal. Total five-hour urinary nitrogen excretions were atypically higher following the high fat test meal than following the high carbohydrate test meal for overweight subjects BM and RT and were slightly higher for underweight subjects NM and EL. Average weight subjects LP, NH and SL had higher total five- hour urinary nitrogen excretions following the high fat test meal, GN, NS and EN had higher total excretions following the high carbohydrate test meal, and RW showed no real difference following the two test meals. Between-Day Variations in Fasting Values Group metabolic patterns were considered in one further aspect. Between-day variations in the fasting observations were evaluated as an indication of the degree of metabolic stability among the subjects. Fasting values of the two experimental days for each metabolite and metabolic product measured were compared and the mean changes for the three groups of subjects were calculated; absolute changes were considered without regard to whether the individual changes were increases or “182 - decreases * These data are tabulated in Table XXIV. The data indicated that day to day metabolic stability is a quality associated to a greater degree with underweight women than with average weight or overweight women. It was recognized that the absolute variation might be related to the magnitude of actual values; higher variations might be expected to be associated with higher actual values. The degree of variation in these data was not consistent with the magnitude of actual values, however; individual variation appeared to be the more important factor. Interrelationships of Metabolic Factors In an attempt to evaluate interrelationships of the various metabolic factors, the data were graphed by a method employing multiple variables adapted from Anderson (1952). These multiple variable scatter diagrams for fasting data and for data of the first, third and fifth hours following both test meals of the overweight, average weight and underweight subjects are presented in Figures 15» l 6 , 17 and 18 . Examination of the data in this way emphasized certain group patterns and individual variations from group trends which have been discussed in previous sections; in addition, interrelationships of the various metabolites and metabolic products between groups and in individuals within groups were readily evident. Figure 15 includes'the fasting non-protein respiratory quotient, energy expenditure, blood glucose concentration, blood pyruvic acid concen­ tration, serum total lipid concentration and hourly urinary nitrogen excretion for each subject for both experimental days. The fasting energy expenditure of each subject was plotted against the corresponding fasting non-protein respiratory quotient; blood glucose, blood pyruvic acid and TABLE XXIV SUMMARY OF THE MEAN DIFFERENCES BETWEEN EXPERIMENTAL DAYS IN FASTING- VALUES OF VARIOUS METABOLITES AND METABOLIC PRODUCTS Subjects Metabolite or Metabolic Product Blood glucose, mg. per 100 ml. Blood pyruvic acid, mg. per 100 ml. Serum alkaline phosphatase, nitrophenol units Total serum lipids, mg. per 100 ml. Serum chylomicrons, count per std. area Serum total cholesterol, mg. per 100 ml. Urinary nitrogen, mg. per hour Non-=protein respiratory quotient Energy expenditure, calories per hour Underweight Average Weight Overweight 5.1 8.2 5.1 0.12 0.15 0.31 0.25 0.21 0.20 66 9^ 32 16 b7 17 23 21 101 85 10L .039 1.8 .068 '+.3 .063 >*.9 -18*4- Figure 15. Multiple variable scatter diagrams of fasting hourly energy expenditures, non-protein respiratory quotients, blood glucose* blood pyruvic acid* serun total lipids and hourly urinary nitrogen excretions for twenty-one women on two test days. Legend: 4X actual size Blood Pyruvic Aeid mg./100 ml. _2.00 ^1.50 .1.00 Blood Glucose mg. /100 m l . k0.50 lOOO Serum Total Lipids mg./ioo ml. 800 A 0 0 6 0 0 ^800 1000 Urinary Nitrogen mg./hour M - Missing value - 185- Calories per hour 80 L Overweight Subjects i — -v i 70 ^ i i 60 L Mr- 60 40 .60 .70 .80 .90 Weight 70 1 60 Average Subjects 80 50 1-1 4 ^ T 40 L__________1__ .60 .70 50 jI 1 ( 40 L_ .60 .70 .80 .90 .80 .90 Underweight Subjects 80 70 60 1 __________J — Non-Protein Respiratory Quotient Figure 16. Multiple variable scatter diagrams of increments from fasting of energy expenditures, blood glucose, blood pyruvic acid, serum total lipids, and hourly urinary nitrogen excretions in relation to non-protein respira­ tory quotients for twenty-one women at the first hour following two test meals. Legend: Figures 16, 17, and 18. 4X actual size Blood Pyruvic Acid mg./lOO ml. 00 Blood Glucose mg./lOO ml. on 30 10 20 Serum Total Lipids mg./lOO ml. 200\ 300 \ 400 ' Urinary Nitrogen mg./hour M - Missing value -187- Test Me a l : High Pat Increment of Calories per hour Test Meals H^gh Carbohydrate Increment of Calories per hour 15 15l >o to +> o © **~5 10 '°L "{5 n -■o- / CO ^ 'T -^n -5 80 0> © .90 1.00 15 .90 1.00 1.10 15 •6 r •rf © E ~o\ 10 10 0 0 © TJ d E> .80 .90 1.00 1.10 Non-Protein Respiratory Quotient .80 .90 1.00 1.10 Non-Protein Respiratory Quotient -188- Test Me a l : High Fat Increment of Calories per hour Test Meal: Increment of Calories per hour 10 10 a> ■p o © •r-3 High Carbohydrate o \r' 5L w Oh 0 © > o .80 . 90 1.00 1.10 .80 .90 1.00 1.10 1.00 1.10 CO g 10 10 &P (O 5 8 •ri • , £ •8m -tpr o 0 9 U © 5 . cf O- n\ 'JD M .80 02 © 10 © ■—3 fO P CO I____________ i .90 1.00 1.10 "O m _ .80 .90 10 M r / O' -*■> •6 «rH © £ O' 0 0 i © E> -5 L .. J_._ .90 1.00 1.10 .80 Non-Protein Respiratory Quotient •5._____ ;______ i. .... .eo .90 i.oo i.io Non-Protein Respiratory Quotient Figure 17. Multiple variable scatter diagrams of increments from fast­ ing of energy expenditures, blood glucose, blood pyruvie acid, serum total lipids, and hourly urinary nitrogen excretions in relation to non—protein respiratory quotients for twenty—one women at the third hour following two test meals. (Legend on page 186) -189Test Meal: Increment of Calories per hour High Fat Test Meal: Increment of Calories per hour 10 10 *> p> o © P CO •a •ri A " 'PM /' -P- A 0 High Carbohydrate 0 A' h © R -5 f O .70 .80 .90 1.00 w ■*» 10 o « *—3 P .70 .80 90 1.00 10 On CO -p 6

-"-8? <0 •H © £ V 'P d .90 P* -O ' 8m P y 0 'P- -5 .70 .80 .90 1.00 Non-Protein Respiratory Quotient .70 .80 .90 1.00 Non-Protein Respiratory Quotient Figure 18. Multiple variable scatter diagrams of increments from fast­ ing of energy expenditures, blood glucose, blood pyruvic acid, serum total lipids, and hourly urinary nitrogen excretions in relation to noxwproteln respiratory quotients for twenty-one women at the fifth hour following two test meals. (Legend on page 186) serum total lipid, concentrations and. hourly urinary nitrogen excretions were indicated by varied lengths of designated appendages to the plotted points. Figures 16 , 17, and 18 are similar scatter diagrams of data for the first, third and fifth hours, respectively, following both test meals. In these Figures, however, energy expenditures, blood glucose, blood pyruvic acid, serum total lipids and hourly urinary nitrogen excretions were all plotted as changes from fasting values. Non-protein respiratory quotients were retained as actual values. In the diagrams of fasting data for the overweight, average weight and underweight subjects in Figure 15, certain interrelationships were apparent. Higher glucose concentrations were associated with lower non- protein respiratory quotients among the overweight and average weight subjects, whereas there was a greater association of higher glucose con­ centrations with high non-protein respiratory quotients among the under­ weight subjects. Lower energy expenditures among the average weight and underweight subjects were somewhat associated with higher non-protein respiratory quotients. There was a greater relative decrease of blood pyruvic acid concentrations than of blood glucose concentrations from over weight to average weight to underweight subjects; the ratio of blood pyruvic acid to glucose was higher among the overweight and lower among the underweight than it was among the average weight subjects. High or low fasting serum total lipid concentrations showed no con­ sistent relationships with other metabolic factors among the groups, although higher blood lipid concentrations were more often associated with lower blood glucose values within groups. Individual subjects who were -191- at the extreme ranges of non-protein respiratory quotient and energy expen­ diture values did not show patterns of glucose, pyruvic acid or total lipid concentrations or hourly urinary nitrogen excretions differing from other individuals within their groups. At the first hour, Figure l6 , differences in relative degrees of change of blood glucose and blood pyruvic acid were evident among the three groups of subjects following both test meals. Following the high fat test meal, increments of both glucose and pyruvic acid were lowest among the average weight subjects, who showed little change from fasting values; glucose elevations were higher and pyruvic acid elevations were lower among the overweight than among the underweight subjects. Following the high carbo­ hydrate test meal, the relative changes of glucose and pyruvic acid were similar among the average and underweight subjects, whereas among the over­ weight subjects the proportion of increment of pyruvic acid to increment of glucose was again low. The highest increments of both glucose and pyruvic acid occurred among the average weight subjects after the high carbohydrate meal; glucose elevations were similar among the underweight and overweight subjects, but pyruvic acid elevations were lower among the overweight than among the underweight subjects. No other relationship among changes from fasting values at the first hour were apparent i there was no interrelationship between non-protein respiratory quotients and calorie increments; non-protein respiratory (juotisnts greater than 1.0 were not associated with consistent changes of other metabolites; elevated serum lipid concentrations following both test meals showed no apparent relation to other metabolic changes, and changes in hourly urinary nitrogen excretions did not appear to be associated with changes of any other metabolic factor. -192- Inspection of the increment data for the third and fifth hours, Figures 17 and 18, revealed no consistent patterns of interrelationships of changes of the various metabolic factors. approached fasting rates or concentrations. By the fifth hour, most values Concerning the hypoglycemia at the fifth hour among the overweight subjects, however, greater decreases from fasting of blood glucose concentrations appeared to be associated with greater decreases of rates of calorie expenditures following the high fat test meal; this relationship was not as apparent following the high carbo­ hydrate test meal. The more consistent group interrelationships discerned among the fasting data than among the increment data at the first, third and fifth hours after the test meals emphasized the greater constancy of postabsorptive metabolic patterns compared to metabolic changes in the absorp­ tive phase. Discussion The interpretation of data of metabolic patterns is difficult because there are individual differences in both the time and intensity of metabolic reactions. Statistical methods for relating the factors of time and degree of change are limited. Variations of individual subjects within the over­ weight, underweight and average weight groups in this investigation corroborated findings of previous studies which have indicated that no single metabolic pattern is associated with the overweight or underweight states. Further, it was not possible to discern consistent patterns of individual variations from group patterns in the data of this study. Nevertheless, certain metabolic patterns associated with the overweight -193- and underweight subjects in this investigation were significently greater than variations among individuals within the groups. The overweight women as a group appeared to exhibit a delay In utilization of carbohydrate, although not of the degree reported for obese subjects with typical "diabetic glucose tolerance curves*5 (Newburgh, 19h2a). There was no question of the ability of the overweight subjects to utilize carbohydrate; a final clearance as complete as that of the other two groups was demonstrated. Following both test meals the overweight group showed a delay in decreasing blood glucose concentrations toward fasting values. The existence of a different stimulus to glucose removal was indicated by the original delay in glucose removal, the significant de­ crease in blood glucose concentrations below fasting values by the fourth or fifth hours, and the significantly higher post-absorptive blood glucose concentrations associated with the overweight group. The significantly lower elevation of blood pyruvic acid concentrations together with mobilization of blood lipids among the overweight subjects following the high carbohydrate test meal likewise indicated the possibility of a different mechanism for the utilization of carbohydrate. Three over­ weight subjects had no increase in blood pyruvic acid concentrations following the high carbohydrate test meal; the other overweight subjects showed blood pyruvic acid increases lower than those of the average weight subjects and subsequent decreases of concentrations below fasting values. A failure of blood pyruvate concentrations to increase in "normal” subjects following glucose infusion with simultaneous administration of glucagon has been interpreted as evidence of a lack of muscle glycogenolysis together with a prompt deposition as muscle glycogen of glucose derived -194- from liver glycogen (Kirtley, et al., 1953 > in. Review, 195^) • Although, "blood pyruvic acid concentrations in tne overweight group decreased below fasting values by the fifth hour, the concentrations were higher than those of the average or underweight subjects in the post-absorptive state and fasting pyruvic acid to glucose ratios were higher among the overweight than among the average weight subjects. Rony and Ching (1930) postulated that carbohydrate metabolism played an important role in the regulation of blood fat concentrations during the alimentary absorption of fat; they reported that the administration of glucose, by mouth or parenterally, or insulin inhibited alimentary lipeaia in dogs. The slower rate of removal of chylomicrons and total lipids following fat feeding among the overweight compared to the under­ weight subjects might further indicate a defect of carbohydrate utilization. The non-protein respiratory quotients provided no real evidence toward clarifying the mechanisms involved; the respiratory quotients, however, increased more slowly following the high fat test meal than those of the average or underweight subjects. Following the high carbohydrate test meal, no difference in non-protein respiratory quotients of the overweight and average weight groups was apparent. The two most overweight subjects in this investigation, RM and SM, were of particular interest because of their respective metabolic patterns. Both subjects had been overweight for many years. Several observations for these subjects made at fasting and following the two test meals were more similar to those for the average or underweight subjects than for those of the other overweight subjects; the metabolic patterns of the t//o subjects were not consistent, hov/ever. Both subjects had lower fasting -195- serum total lipids, total cholesterol and chylomicron concentrations than those of the other overweight subjects, although serum lipoprotein concen­ trations were high. Basal energy expenditures were significantly lower than those predicted by the calculated line of regression. RM had one of the lowest fasting glucose concentrations among the overweight subjects and a low one-half hour maximum blood glucose concentration following the high carbohydrate test meal. Fasting blood pyruvic acid concentrations were relatively low on both days for RM, whereas subject SM had a low value on one day and a very high value on the other. Although RM showed no increase in blood pyruvic acid following either meal, SM showed some increase following both test meals. Neither subject showed any increase in chylomicron concentrations after the high carbohydrate meal. And, SM had a decrease in serum total lipid concentration at the first and third hours after the high carbohydrate test meal. These observations might indicate that some degree of metabolic adjustment had occurred in these subjects during a prolonged overweight condition; evidences of physio­ logical abilities to adjust to low planes of nutrition have been reviewed (Mitchell,' 1 9 ^ ) . The underweight subjects as a group displayed a metabolic pattern which differed less from that of the average weight subjects than that of the overweight group, but there were some indications of a preferential utilization of carbohydrate. The ratio of fasting pyruvic acid to glucose concentration was lower than that of the average weight subjects. Follow­ ing the high fat test meal, particularly, blood glucose concentrations showed lower elevations and decreased to fasting values more rapidly than those of the average weight subjects; concurrently, non-protein respiratory -196- quotients and blood pyruvic acid concentrations showed the most marked elevations of any group and the most rapid decreases to fasting values. Although chylomicron and total lipid concentrations increased to the greatest extent of any group, the rate of removal of these lipids from the blood was most rapid. Following the high carbohydrate test meal, some trend for an early removal of blood glucose was observed and non—protein respiratory quotients were elevated longer than those of the other groups. Significantly higher cumulative calorie increments following the high fat test meal, signifIcantly lower cumulative nitrogen excretions for five hours following both meals and less between-day variations in fasting values were characteristic of the underweight subjects. The number of subjects investigated and the individual variations observed limited the interpretation of the data relative to differences in fat and carbohydrate metabolism among the overweight, average weight and underweight subjects. Increased numbers of subjects undoubtedly would clarify group metabolic patterns in relation to individual metabolic patterns; the inclusion of a greater proportion of subjects whose weights were at the extremes of deviations from desirable weight might clarify types of individual metabolic patterns within the overweight and under­ weight groups. A clarification of patterns of fat and carbohydrate metabolism among the overweight and underweight individual might be gained also by more frequent measurements of blood glucose, blood pyruvic acid, blood lipids, energy expenditures and non-protein respiratory quotients, particularly during the first and second hours. A variable factor in this investigation was the disproportional distribution of calories from carbohydrate and fat in the two test meals. The high carbohydrate test meal provided 95 percent of the calories from carbohydrate, but the high fat test meal pro­ vided only 70 percent of the calories from fat, Carbohydrate was included in the fat test meal to increase its acceptability to the subjects. Test meals in which the calories from fat and carbohydrate were exactly reversed might be a sounder basis of comparison of metabolic changes following the two test meals. It is suggested that test meals in which approximately 70 percent of the calories were provided by fat and carbohydrate, respectively, should yield more representative data of metabolic patterns than relatively pure fat or pure carbohydrate feedings. SUMMARY Metabolic patterns of a group of overweight, underweight and average weight women were investigated at fasting and following two test meals of varying carbohydrate and fat composition. Twenty-one apparently healthy women from twenty-five to fifty-seven years of age served as subjects; their weights ranged from 466 to -21 percent of desirable weight. On the basis of deviations from desirable weights, the women were grouped into three classesJ seven overweight subjects, +66 to 421 percent of desirable weight; seven average weight subjects, 413 to -10 percent of desirable weight; and seven underweight subjects, -12 to -21 percent of desirable weight. The test meals each provided approximately four hundred and fifteen calories; in the high fat test meal, fat, carbohydrate and protein contributed 70, 25 and 5 percent of the calories, respectively, whereas in the high carbohydrate test meal, fat, carbohydrate and protein, respectively, contributed 0.5, 9^*5 5 percent. Respiratory quotients, hourly energy expenditures, concentrations of blood glucose, blood pyruvic acid, serum alkaline phosphatase, serum total lipids, serum total cholesterol, certain serum lipoprotein classes and serum chylomicron counts and hourly urinary nitrogen excretions were determined at fasting. Following the test meals, respiratory quotients, hourly energy expenditures and hourly urinary nitrogen excretions were determined simultaneously with blood glucose, blood pyruvic acid, serum total lipids and serum chylomicron concentrations at the first, third and fifth hours; blood glucose and serum chylomicron concentrations were determined additionally at the one—half, second and fourth hours. - 199 - The mean basal energy expenditure of the overweight subjects was significantly higher than that of the average weight subjects and the mean basal energy expenditure of the underweight subjects vras signif icantly lower than that of the average weight subjects. The hourly mean basal calorie expenditures were 65 , 52 and h7 for the overweight, average weight and underweight subjects, respectively. Mean fasting non-protein respiratory quotients were not significantly different among the three groups, although lower respiratory quotients were found among the over­ weight subjects than among the other subjects; the mean non-protein respira­ tory quotients of the overweight, average weight and underweight groups were 0.79, 0.83 and 0.83, respectively. Fasting blood glucose concen­ trations were significantly higher among the overweight than among the average weight or underweight subjects; the mean values were 93 , 83 and 81 milligrams per 100 milliliters, respectively. Fasting blood pyruvic acid concentrations were significantly higher among the overweight subjects than among the underweight subjects, but neither group mean was signifi­ cantly different from that of the average weight group; the mean fasting concentrations were 1.22, 1.02 and O .85 milligrams per 100 milliliters for the overweight, average weight and underweight subjects, respectively. There were no significant group differences in mean fasting venous serum alkaline phosphatase or in mean fasting concentrations of the various serum lipid constituents, capillary or venous serum total lipids, serum total cholesterol, serum lipoprotein classes Sfl2-20, 21-35 a ^d 35-100, or in capillary or venous serum chylomicrons. Hourly fasting urinary nitrogen excretions were lower among the underweight subjects than among the overweight or average weight subjects, but there were no significant -200- group differences. The mean fasting hourly nitrogen excretions of the overweight, average weight and underweight subjects, respectively, were 550, and 350 milligrams. Group mean observations of the overweight, average weight, and under­ weight subjects for all intervals measured on both test days are graphically summarized in Figure 19. Following the high fat test meal, the hourly calorie expenditures of the overweight subjects were consistently higher at every hour than those of the average or underweight subjects; the cumulative energy incre­ ments for five hours, however, were significantly higher among the underweight subjects than among the average weight or overweight subjects. The non-protein respiratory quotients of the overweight subjects increased more slowly than did those of the average or underweight subjects and maximum quotients were lower; quotient increases were highest among the underweight subjects. Blood glucose concentrations increased more slowly among the overweight subjects than among the average or underweight subjects; blood glucose concentrations of the overweight subjects then decreased to concentrations significantly below fasting values at the fourth and fifth hours. Blood pyruvic acid changes were slight among all groups and there were no significant group differences, although the underweight subjects showed a greater first hour increase and the over­ weight subjects showed a greater third hour decrease in concentrations. Underweight subjects displayed a distinct increase in serum lipid concen­ trations from fasting to the third hour and then a decrease toward fasting; serum total lipid concentrations among the average and overweight subjects showed gradual, lesser increases with little or no subsequent -201- Figure 19. Summary of moan metabolic patterns for over­ weight, average weight and underweight subjects. Legend: Overweight Subjects ------ Average Weight Subjects --------UnderweightSubjects -202- Test Meal: 60 40 .90 .70 140 100 60 ..50 .50 800 600 400 200 0 450 High Fat Test Meal: High Carbohydrate decrease. Ghylomicrographs showed, distinct pattern differences among the underweight and overweight subjects; chylomicrographs of the average weight subjects were generally typical of those of either the overweight or underweight subjects. Among the underweight subjects, chylomicron concentrations showed a significant initial one-half hour rise, reached the highest peak concentrations, and then decreased most rapidly. In the overweight subjects chylomicron concentrations increased more slowly, reached lower peak concentrations, then maintained near-peak concentrations throughout the remainder of the five hours. Mean hourly urinary nitrogen excretions were generally decreased from fasting values in periodic collections among all three groups; changes among the overweight subjects, who had the highest fasting hourly excretions, were the most irregular. The mean total urinary nitrogen excretion of the underweight subjects for five hours following the high fat test meal was signif icantly lower than those of the average or overweight subjects. Following the high carbohydrate test meal, the hourly calorie expenditures of the overweight subjects were again consistently higher at every hour than those of the average or underweight subjects; cumulative calorie increments above basal for five hours were higher among the over­ weight and average weight subjects than those following the high fat test meal, but were lower among the underweight subjects. Non-protein respiratory quotients of the underweight subjects appeared to reach peak values later than those of the average weight or overweight subjects and quotients generally remained elevated above fasting values longer, measured non-protein respiratory quotients showed no significant differences among the three groups, however. Overweight subjects had the highest one-half hour blood glucose concentrations in response to the high carbo­ hydrate test meal; at the fifth hour, glucose concentrations of the over­ weight subjects were significantly below fasting concentrations. Blood pyruvic acid concentration increases from fasting values were significantly lower among the overweight subjects than among the average weight subjects; changes from fasting concentration were not significantly different among the average weight and underweight subjects, although the mean increase for the underweight subjects was less than that for the average weight subjects. Mean serum lipid concentrations were increased from fasting in a greater amount following the high carbohydrate test meal than following the high fat test meal among the overweight subjects; serum total lipid concentrations increased only slightly among the average weight subjects and decreased among the underweight subjects following the high carbo­ hydrate test meal. Chylomicro graphs of the mean data of the average weight end underweight groups were characterized by no hourly changes; the chylomicrograph of mean data of the overweight group showed significant peaks at the one-half and the third hours. Mean hourly urinary nitrogen excretions were decreased from fasting to the greatest extent among the overweight subjects, to a lesser degree among the average weight subjects and least among the underweight subjects. Total urinary nitrogen excretions for five hours following the high carbohydrate test meal were significantly less among the underweight than among the average or over­ weight subjects. Certain group interrelationships of metabolites were evident. There was an association of higher fasting glucose concentrations with lower fasting non—protein respiratory quotients among the overweight subjects -205- and higher fasting glucose concentrations with higher fasting non-protein respiratory quotients among the underweight subjects. The ratio of fasting blood pyruvic acid to fasting blood glucose was higher among the overweight and lower among the underweight than it was among the average weight subjects. At the first hour, the ratio of increments from fasting of blood pyruvic acid to blood glucose concentrations were highest among the average weight and underweight subjects and lowest among the overweight subjects following the high carbohydrate test meal; following the high fat test meal, the ratio of pyruvic acid to glucose increments was highest among the underweight and least among the average weight and overweight subjects. Individual variations from all group metabolic patterns occurred. No consistent patterns of individual variations could be discerned. CONCLUSION Certain differences in metabolic patterns were observed among the overweight, underweight and average weight women in this investigation at fasting and following two test meals. The overweight women as a group appeared to exhibit a delay in utilization of carbohydrate in the test meals compared to the average weight and underweight women. 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Lipoprotein Classes Subject SfO-11 Spi2-20 Sf21-35 Sf35-100 RL — — 21 7 16 RK —— — 3 2 5 140 12 2 --- 43 13 21 SL Sf100-400 h Analyses were obtained on two days for some subject aad on one day for others; no lipoprotein analyses obtained for subjects RT, NH and SL. -2*4-1- H (0 © £ 49 w vn «> EH © +> rt 41 >* o ,0 u co> © o oo >h g E-i EH O EH ! zj o © 49 u © p« o o s 0 O, § s iH CV1 a rH 00 c n a rH -ao o oO a a o o o 00 a n CM CN -R a a CM H CO CM H O NO • o a H • • • * « rH rH O O O O O © R 00 n Q XT\-^t CO ON ON I -3- rH rH NO O rH i—IO o o rH £ *ri O © © -R n o V N C O C M CN- o O NO o -rt" O ON NO a a a a a • © H C M ir-4 H H H H « « © EH 49 © to 00 COi ttf U © 4» v-i '**! OB rH O W 4I» M) OB R © **H to 4* O © *r-a rt tn CO • © © O nOn CO Q On CO 0 \N • »t O O * » O rH rH rH VN VN » rH CN- O '- CO O C n - ON H-t ON N O C- CM rH -3* UN,-rt" O> f t * © * * * • NO rH O CD rH O O n rH O rH H rH O NO 0 0 ON CO H CO 0 0 N tN C O ON* VN Ov CO CM NO Cvl • « * * • • O H O O H H H © O R ,Q y^riiCHiH o hi >TlCO O ON N H O H s rH rH tf=H O O HI O O rH O » • • • » * * rH O C © © © X ttf) & © O © On O IN- On O vO H O O H H O O o o cn co -R o -R ONa ONa Oa ONa Na H a C-a O O H o O H o &cvl -R ^ CNrH H CO r\ o- o I5 0 0• O N* N • rH O rH o o o O- H V\VN Cn- £"-CO 00a Csal ONaCO CnCnvn a a a a O H OO O O O CO ON ON H CM On O n H © O 00 rH»NO* H O NO O n n On O n H O On CO xi © o -R H H H»I ON CM •H • • H O H H pO O N H pO N H 4" O H O CO •CO O NO On H H O determinations o o 1 o < o I—« rH oo oa CoNa o 1— « r H * © O - V N O N C N CM 0 0 rH V N O CN) r N O n Cna a a a a a a CO HI H H H O O O © O On 00 rH VNNO CM CN O O n10$ pq •-4 EH *<; CO fe5 O M Ei d ) r-H rH IX)o H CM H C M S C - C . O V differ u © pq E-* Sa? X rH O O N *§> •H m t- § O H O GO VC VN 0- O f'•J CO• H* H• CvCO• ON• • rH O f'H t—I O O O Duplicates C/1 t> © c^. r-r^- cm \o o n•- ^• o •n o• n ♦c ^• o -3© © & £ m § s a ta O - 242 - TABLE XL FASTING SERUM ALKALINE PHOSPHATASE CONCENTRATIONS ON TWO TEST PAYS Serum Alkaline Phosphatase Subject Nitrophenol units RM SM RM HT RT MR YL 1.35 1.60 1.25 1.16 1.90 1.50 0 .9 2 1.80 1.50 I.65 1.10 1 .8 4 1.65 1.12 GN IP NH RW SL NS EN O.65 0.9 5 2.25 1.29 1.15 1.45 1.60 0.80 0.90 2.05 0,86 0.90 1.20 1.45 RD NM YK RL RK EL NL 0.90 0 .8 4 I.65 1.00 1 .3 6 1.20 1.0? O.85 1.45 0 .9 2 1 .4 8 2.12 1.40 _ _ -2^3- Cv- m m o\ H O N \Q O CM vo CO CMvf l CM CM rH CM rH _ 0} -d m v o H 4 S m m - d -CO m CM d CM C^-vO ^ V O GO CO nfr < n -d m v O 00 rH -d m e n d on m m » w O vo O N On H rH CM V\vO N O O H CO CM rH 00 rv- O v rH O n CM rH rH CM rH OV OV \T\00 On H H «30 d CM C V M) M) H H m CM VP\m Ovd H H CM rH vO H IN »A H H CNJ UN, ^ \N 4 -M ) Q N O cn cn d c*~v -ct- -2F Qv O m CV ov cn Cv. d O-VO OO o v o v Ov m CM CM CM CM CM CM O - rH CM V O d v O d C V O n H n£) v o CM CM rH O v \ n Cv- #H CO O m o mvO h 4 N -3 c n m m d cm m -3--3" £ V A C ^ N O OV © N H Ov e n rH CO m v O m m d vo °o o q> d 00 CO m n cm fiv- v r \ d 3" v o © m m CM Ov CM m CM HI O C V O v rH Cr\ 2 VT\ m m d (8 v m s rH rH on m d m o m o m oo oo ov rH v O 4 n m m d m v o o n ,d N CO »C| On H OQ nO m o m m cn m m en m CO Ov moo w m N N m ov co d CM rH vo r ^ a p ov d m d CM Ov m m CM m cm rH £ u u> o 09 > d •rH 4-» ■H 4-3 rH © o Em <8 a ^ g o o p4 0Q U 3 o tn m cm m VO o d vo CM CM rHov m CMH oo rH CM rH cv. cm d t>CM d c v -o - rH rH ctv d m v p n- d m CM rH rH m m CM d m oo oo o oo m rH CM CM rH CM rH rH H ONOn® Q n N H V O rH ^ in- rH m d rH d Ov rH vo d rH rH rH irH rH rH rH +» 0$ d 09 V b pe» !*3) uw S CM f- O m H d eS woo m n o m H N m m m m Ov rH rH O v rH c n O n CO V O Q n d O n H O cm CM CM CM CM CM CM CM u O +* CO 4 CMvO O n v O o d m ov d m m vo m m m 3 O IN- cv- rH m d o v Cv- CM m m v£) rH rH w tu q d dr d Ov v o N cm Q rH c m m vB m n d M) d d m m CM rH m d m 0O 00 O rH rH CM Ov O- rH m m m cm c m m cm rH CO >3 rH +> 09 O rH W S m cm m m m cn cm ^ m O N d rH rH rH rH Ov VPN 00 00 envo m cn d d cm (8 Ov m rH CM m O v Ov rH cn O H 00 09 W) oft d (k, ^ d O m o o v p C- rH Cv- vjO CM m d rH 00 s O v O d 00 CM d CM m m m d d m ) 5$ •o u m +» © h N cm d differ n d o © &H S m Q m N O rH cn m m rH OS i4<-3D s O o -v o m d m O V Ov O m cm cm m ’Duplicates •rH m Trf cm a ■*» o © *«"a ■3 co X CO EH EH m pi g s g s t A CO m - 2^ 4- CASE HISTORIES Subject RM. RM was 39 years of age and was evaluated, to be sixty— six percent above desirable weight. The rate of fasting energy expenditure was significantly lover than that predicted by the calculated line of re­ gression, although the actual rate of energy expenditure was the highest of all subjects. Pasting non—protein respiratory quotients were higher than the mean of the overweight subjects, while fasting blood pyruvic acid concentrations were lower than the group mean. Fasting serum lipoprotein fraction Sf12-20 and Sf 35~100 concentrations were greater than 80 and 50 milligrams per 100 milliliters, respectively. Following the high fat test meal, responses were generally typical of the overweight group; serum total lipids were increased from fasting at all hours measured. Following the high carbohydrate test meal, the one-half hour blood glucose concentration was low and deviated markedly from the rest of the group; blood pyruvic acid concentrations showed no increase from fasting values; serum total lipids were increased above fasting through the third hour and then decreased markedly at the fifth hour; chylomicron concentrations, however, showed almost no hour to hour variation. Total urinary nitrogen excretion was higher following high fat than high carbohydrate test meal. Subject SM. SM was 53 years of age and was evaluated to be fifty-eight percent above desirable weight. The rate of fasting energy was slower than that predicted by the calculated line of regression; the concentration of Sf12-20 fraction of serum lipoproteins was greater than 50 milligrams per 100 milliliters; other fasting values were typical of the overweight group but between day variation in blood pyruvic acid concentration was very high. Following the high fat test meal, the increase in rate of energy expenditure was high, serum total lipids showed a marked increase in concentration to the third hour, and blood pyruvic acid was increased to the greatest extent of the overweight subjects. Following the high carbohydrate test meal, energy expenditure and non-protein respiratory data were not obtained for the fifth hour; at the first hour the non­ protein respiratory quotient was 1 .01 ; chylomicron concentrations showed little hour to hour variation; and serum total lipid concentrations were decreased from fasting value at the first and third hour, but were increased above fasting at the fifth hour. Subject HM. HM was 30 years of age and was evaluated to be thirty-one percent above desirable weight. Fasting values were generally typical of those of the overweight group; chylomicron concentrations were the highest of any subject, however; pyruvic acid concentrations were somewhat low, but only single determinations were made; between day variation for all values was very slight. Following the high fat test meal, the increase in energy -2^5- expenditure was low; the fifth hour serum sample was extremely creamy and the chylomicron count at that hour was extremely high; serum lipid concen­ trations were not changed. Following the high carbohydrate test meal, responses were generally typical, HM had a very marked increase in serum total lipids and erratic changes in serum chylomicron concentrations; blood pyruvic acid concentrations showed no increase from fasting value. Subject HT. HT was ^5 years of age and was evaluated to be twenty-nine percent above desirable weight; she was in a period of active weight gain. Fasting values were generally typical of the overweight group means; fasting hourly urinary nitrogen excretions were, however, extremely high and .fasting cholesterol concentrations were 282 and 2*42 milligrams per 100 milliliters for the two test days, respectively. Following the high fat test meal, responses were generally typical of the group; non-protein respiratory quotient showed a marked elevation at one-hour, however; serum total lipid concentration was markedly reduced at the first hour; and the change in serum chylomicron concentration was the least of any subject. Following the high carbohydrate test meal, hourly energy expenditure was markedly decreased from the first to third hours, maximum non-protein respiratory quotient measured was at the third hour, serum chylomicron concentrations were highly erratic, while serum total lipids were increased at the first hour and then gradually were decreased. Cumulative calorie increments measured for five hours were greater after the high fat test meal but low following either. Subject RT. RT was 57 years of age and was evaluated to be twenty-two percent above desirable weight. Fasting values were typical of the overweight subjects, except that fasting hourly urinary nitrogen excretions were low and serum chylomicron concentrations were low for the overweight group; fasting serum total lipid concentrations were greater than 1000 milli­ grams per 100 milliliters and fasting cholesterol concentrations were 258 flucl 311 milligrams per 100 milliliters. Following the high fat test meal, hourly energy expenditures continuously decreased from fasting value, blood glucose showed a definite one-half hour peak concentration, the chylomicrograph was typical of overweight subjects and hourly urinary nitrogen excretion was markedly increased at first hour. Following the high carbohydrate test meal, responses were generally typical of the over­ weight group; chylomicron concentrations, however, showed no hour to hour irregularity, although serum total lipid concentrations were markedly increased. Total urinary nitrogen excretion for five hours was greater following high fat test meal. Subject MR. , , . MR was 29 years of age and was evaluated to be twenty-two percent above desirable weight. Fasting non-protein respiratory quotients were very low and fasting blood glucose concentrations were both near 100 millip’ams per 100 milliliters of blood; other values were typical of the overweight group. Following the high fat test meal, the non-protein respiratory quotient Increased to the third hour, but was never greater than 0.79; blood -246- pyruvic acid was decreased from fasting value at the first and third hours; cumulative calorie increments for five hours were higher following the high fat test meal than the high carbohydrate meal; the chylomicrograph was typical of the underweight subjects. Following the high carbohydrate test meal, non-protein respiratory quotient was 1.10 at one hour and still elevated above fasting value at the fifth hour; tile one-half hour blood glucose concentration was the highest of all subjects; serum total lipids were decreased at one hour but then increased at the third and fifth hours, while chylomicron concentration displayed erratic increases arifi decreases. Subject YL. YL was 25 years of age and was evaluated to be twenty-one percent above desirable weight; she was in a period of active weight gain. Fasting values were all typical of the overweight group; fasting energy expendi­ ture and non-protein respiratory quotients showed marked day to day variation. Following the high fat test meal, responses were generally typical of the overweight group, although cumulative calorie increments for five hours were similar after both the high fat and high carbohydrate test meals. Following the high carbohydrate test meal, responses were again generally typical of the overweight group; serum total lipids and chylomicron concentrations both showed marked increases at the third hour; hourly urinary nitrogen excretion was increased from fasting value at the first and the first to third hours; there was no change in blood pyruvic acid concentration. Subject GH. GN was 38 years of age and was evaluated to be thirteen percent above desirable weight. Basal energy expenditure was slightly below that pre­ dicted by the regression line; the fasting serum total lipid concentration was high and serum total cholesterol concentration was greater than 300 milligrams per 100 milliliters; other fasting values were within average weight group range and showed very minimum day to day variation except for basal energy expenditures. Following the high fat test meal, non-protein respiratory quotient was above fasting value at the fifth hour; the chylomicrograph was of the overweight pattern; blood pyruvic acid concentration showed a gradual increase at each hour; other responses were typical of the average weight subjects. Following high carbohydrate test meal, one-half hour blood glucose concentration was low and third, fourth and fifth hour values were below fasting value. Total urinary nitrogen excretion for five hours was higher following high carbohydrate test meal than following high fat test meal. Subject IP* LP was <^0 years of age and was evaluated to be six percent above desirable weight. Fasting values were typical of those of the average weight group, but between day variation was high for basal energy expendi­ ture, fasting non-protein respiratory quotients and serum total lipids. Following the high fat test meal, cumulative calorie increment above fasting was the highest of any subject and greater than that following high carbohydrate meal; non-protein respiratory quotient showed little change from fasting; the chylo micrograph was typical of the overweight subjects. Following the high carbohydrate test meal, all responses were generally typical of the average weight group, but non-protein respiratory Quotient was below fasting value at fifth hour. Total urinary nitrogen for five hours was higher after high fat than high carbohydrate test meal. Subject NH. 7JH was 52 years of age and -was evaluated to be about two percent above desirable weight. Her fasting energy expenditure was slightly below that estimated by the regression line; fasting serum total lipids and serum total cholesterol were the highest of all subjects; other fasting values were within group ranges. Following the high fat test meal, non-protein respiratory quotient showed no change at the first hour, then decreased continuously at the third and fifth hours; chylomicron concentration changes were typical of the overweight subjects; serum total lipids showed marked and continuous increase throughout the five hours; and hourly urinary nitrogen excretions showed no decrease from fasting value. Following the high carbohydrate test meal, the one-half hour glucose con­ centration was highest of average weight group, fifth hour non-protein quotient was decreased from fasting value; serum total lipids increased markedly from the first to the third hours and then decreased, and hourly urinary nitrogen excretions showed no decrease from fasting value. Total urinary nitrogen excretions for five hours were higher following high fat than high carbohydrate test meal. Subject RW. RW was 37 years of age and was evaluated to be at desirable weight. Fasting non-protein respiratory quotients were low and fasting chylomicron counts were low for the average weight group; other fasting values were typical. Following the high fat test meal, expired gas samples were lost for the first hour and serum total lipids were not determined; the chylomicrograph was typical of the underweight subjects; the non-protein respiratory quotient was markedly above fasting value at the fifth hour. Following the high carbohydrate test meal, serum total lipids were determined at the second, fourth and fifth hours; both the second and fifth hour samples showed serum total lipid concentrations elevated from fasting. Non-protein respiratory quotient was similar to fasting value by the third hour following carbohydrate meal. Total urinary nitrogen excretions were similar following both test meals. Subject SL. SL was 25 years of age and was evaluated to be seven percent below desirable weight. Subject SL had the lowest calorie per hour expenditure of the average weight subjects; hourly energy^expenditure slightly below that estimated by regression line; other fasting values were typical. Following the high fat test meals the non-protein respiratory quotient was below fasting value at the fifth hour; the chylomicrograph showed no change at one-half hour and then the highest one-hour peak concentrations. Serum total lipids were not determined. Following the high carbohydrate test meal: the non-protein respiratory quotient peak above 1.0 was delayed until the third hour; there was the most pronounced decrease 01 blood^glucose concentration below fasting of average weight subjects; pyruvic acid concentrations were depressed below fasting at all hours measured; serum total fats increased and the chylomicron concentrations were slightly elevated from fasting. Total urinary nitrogen excretion for five hours was higher following high carbohydrate than high fat test meal. Subject NS. NS was 29 years of age and was evaluated to be seven percent below desirable weight. Fasting values were all typical of the average weight group. Following the high fat test meal, the chylomicrograph was typical of overweight subjects; the non-protein respiratory quotients, blood glucose and pyruvic acid concentrations, serum total lipids and hourly urinary nitrogen excretions were typical of average weight group, though highest non-protein respiratory quotient was at third hour. Following the high carbohydrate test meal serum total lipids were not determined; responses measured were typical of the average weight group, except that hourly urinary nitrogen excretions showed little decrease from fasting values. Total urinary nitrogen excretion for five hours was higher following high carbohydrate than high fat test meal. Subject EN. BN was 32 years of age and was evaluated to be ten percent below desirable weight. Fasting values were typical of the average weight pattern. Following the high fat test meal, no increased calorie response to the test meal was measured until the fifth hour; the chylomicrograph was typical of the underweight subjects: other responses were typical of average weight subjects. Following the high carbohydrate test meal: calorie expenditures, non-protein respiratory quotients, blood glucose and serum chylomicron concentrations were typical of those of the average weight group; blood pyruvic acid changes were typical of those of the average weight group, but the peak concentration was the maximum value determined for any subject; serum lipid concentrations decreased. Total urinary nitrogen excretion for five hours was higher following high carbohydrate than following high fat test meals. Subject ED. ED was 51 years of age and was evaluated to be twelve percent below desirable weight. Fasting values were all typical of the group pattern except serum total cholesterol concentrations which were 235 and. 233 milligrams per 100 milliliters on the two days. Following the high fat test meal, peak glucose concentration was delayed to the first hour; the blood pyruvic acid concentration increase at one hour was the greatest of the underweight subjects. Following the high carbohydrate test meal, the blood glucose concentration increased to 185 milligrams per 100 milli­ liters of blood at one—half hour, decreased slowly until the second hour, then decreased sharply to below fasting concentrations at the third hour; the non-protein respiratory quotient increased to 1.15 at the first hour. Other metabolic responses to the test meals were typical of the under­ weight group. -2h9~ Subject NM. NM was hO years of age and was evaluated to be thirteen percent below desirable weight. Fasting values of all constituents measured were typical of the underweight group, except fasting hourly urinary nitrogen excretions, which were low and lipoprotein fraction S^12-20 concentrations which were somewhat high. Following the high fat test meal, the chylomicrograph of HM was typical of the overweight rather than that of the underweight subjects; peak concentration was delayed and there was no decrease toward fasting concentrations during the five hour period. Following the high carbohydrate test meal, the blood glucose concentration was 182 milligrams per 100 milliliters at one-half hour; the renal threshold for glucose of the subject was exceeded during the first .hour and during the first to third hours. Following the high carbohydrate test meal, the serum total lipid concentration showed the most marked decrease from fasting of that of any subject and total urinary nitrogen excretion for five hours was slightly less than following high fat meal. Tot.nl cumulative calorie increments above fasting for the five hours after feeding were higher folloxving the high carbohydrate test meal then follow­ ing the high fat test meal. Subject YK. YK was 51 years of age and was evaluated to be fourteen percent below desirable weight; YE was Mactivelyw losing weight. The lowest measured basal energy expenditure was that of YK, ^2 calories per hour. Only single basal energy expenditure and respiratory quotient values were obtained for each experimental day; the between day variations were marked. Fasting blood pyruvic acid concentrations were the highest of the underweight group; fasting serum lipoprotein fractions S^.12-20 and S^35“l°0 concen­ trations were relatively high. Other fasting values were typical. Following the test meals, certain responses were atypical of the under­ weight group. Non-protein respiratory quotients following both test meals increased to a greater extent than those of any other underweight subject; peak quotients also occurred at later hours. The chylomicrograph following high fat feeding was typical, but peak concentration was delayed to the third hour. Total cumulative calorie increments above fasting for the five hours after feeding were higher following the high carbohydrate test meal than following the high fat test meal. Blood glucose concen­ trations of one-half hour following high fat test meal was not changed from fasting value; one hour blood glucose value following high carbohydrate test meal was below fasting concentration. Subject RL. RL was 3h years of age and was evaluated to be fifteen percent below desirable weight. Fasting respiratory quotients were low for the under­ weight group. RL responded with the lowest non-protein respiratory quotients following both test meals. In both cases acetone bodies were excreted in the third to fifth hour urine collections; traces of acetone substances were indicated in the first to third hour urine collection following the high fat test meal. Other fasting values and metabolic responses measured showed no unique pattern. Fasting serum total cholesterol concentrations were relatively high, however, 2oh and 369 milligrams per 100 milliliters. Following the high carbohydrate test meal, serum total lipids were decreased markedly at the first hour; subsequent measurements were made at the second, fourth and fifth hours and showed consistant increases toward fasting concentrations. Subject RK. RK was 25 years of age and evaluated to be seventeen percent below desirable weight. Fasting glucose and fasting chylomicron concentrations were in the upper range of the underweight group; fasting serum total lipid concentrations were the lowest. Following the high fat test meal: the energy increment response was low; blood pyruvic acid concentration showed no change; chylomicrograph was generally typical, but the peak serum chylomicron concentration was the highest measured for any subject, and the maximum total blood lipid response was quantitatively low but typical in terms of percent of fasting concentration. Following the high carbohydrate test meal responses were generally typical, except that the rate of energy expenditure was the most erratic of the group; chylomicron counts were relatively erratic and the decrease in hourly urinary nitrogen excretion was the most marked of the underweight subjects. Subject EL. EL liras 27 years of age and evaluated to be seventeen percent below desirable weight. One fasting non-protein respiratory quotient of 0.79 was low for the underweight group. The high fasting chylomicron count measured on the first experimental day appeared to be the result of the ingestion of two doughnuts by the subject late in the evening prior to that experimental day. Following the high fat test meal, EL had the highest increase in serum total lipids of all underweight subjects; other responses conformed to group pattern. Following the high carbohydrate test meal: serum total lipid values were not determined; urinary nitrogen excretion was slightly lower than following the high fat test meal; and blood glucose concentration was maximum at one-half hour, decreased at the first hour, increased again at the second hour and then decreased below fasting at the fifth hour. Subject NL. NL was 27 years of age and evaluated to be twenty-one percent below desirable weight. Her fasting energy expenditure deviated from the rest of the underweight group; the hourly rate of calorie expenditure was significantly higher than that estimated by the regression line. Hourlyfasting urinary nitrogen excretions were low. Other fasting- values con­ formed to the group pattern. Following the high fat test meal, chylomicron concentrations reached a high peak concentration at the second hour; the serum sample was visibly milky. Serum total lipids showed the smallest increase in concentration of all underweight subjects and then fell below fasting concentrations; serum total lipids were determined, at the one-half, first, second, fourth and fifth hours because sufficient serum was not available at the regular intervals. The third hour calorie increment was greater than that of the first hour. Other^ responses following the high fat test meal were typical of the underweight ^roup. Following the high carbohydrate test meal, metabolic responses generally conformed to the group patten*; however, a positive qualitative super test was found for the first hour urine collection (estimated, 0.l£) -whereas the one-half hour blood glucose value was relatively low. -251- Directions for Subjects We should like to request your cooperation for two separate days from early morning until approximately 2:00 P.M. On the day preceding an experiment, no food should be con­ sumed after 7 P.M. and supper should be as low in fats as possible. (Do not eat fats as butter, mayonnaise and salad dressing, cream, gravies, or rich desserts.) Eight hours sleep should be obtained on the night preceding an experiment. On arising in the morning, the bladder should be emptied as completely as possible and the time noted. (This should preferably be by 6:45 A.M.) Please drink a glass of water and then do not urinate again until after you come to the laboratory. Please arrive at the laboratory by 7:15 A.M. in activity! Be leisurely You will be asked to rest quietly (lying or sitting) during the experimental period. Bring reading matter or hand-work, if you desire. ‘ A test meal breakfast will be served. Basal metabolism tests collections of blood and urine samples will be made during the course of the experiment. -25 2- DIBT HISTORY Name Date, Address______ ___ Birth date Age Place of birth Sex. _____ __ ____________ _______ Nationality Are you a citizen of the U.S.7, Father *s birthplace. Mother®s birthplace. How many generations has your family lived in the U.S.?. How many members are there in your family?. Do you live in a) Country b) Small town Have you always lived here? Yes lived most of your life? ___ No If not, where have you __________ Do you eat vegetables? . Fresh? Do you usually eat vegetables? (a) Once per day?_____ c) City^ ___ Twice per Canned?. _ Yes_ day?_ _ No_ More?. (b) What vegetables do you dislike? .___ __ (c) Favorite vegetables^ ___ Do you eat potatoes? ___ — _ Yesg (a) Once per day? Twice per „— How often? Once or twice per day? Do you eat fruits? Yes No No__— _ More?__ (b) Favorite method of preparation^, iju ui-_ Do you eat any vegetables raw? — .— .... — Yes__-- — ± Several times per w e e k ? „ _ Fresh____ C a n n e d _ _ Dried, -253- Do you usually use some fruits In your diet? Yes, (a) Once per day? Twice per day?. No More? (b) What fruits do you dislike? (c) Favorite f r u i t s ____ Do you eat meat? Yes No H ow often do you plan meat in your diet? Once per day. Twice per day? Several times per week?. Do y o u buy (a) liver? No Yes, (b) kidney? Yes, No, (c) brains? Yes No sweetbreads? No Yes H o w often do you eats Once per week? Once per month. Lesji (b) brains? Once per week? Once per month. Less (c) kidney? Once per week? Once per month. Less. (d) sweetbreads? Once per month. Less (a) liver? w M What meats do you dislike? Favorite meat___ Do you eat fish? No Yes Several times per week?. Once per week? Do you drink milk? (a) Yes, No H ow many glasses per day?. Do you use cream? (a) Yes. No Sparingly, (b) Liberally, Do you eat eggs every day? Yes. No No. per week(average) Do you ©at cheese regularly? Yes No Kind of cheese _ Do you eat cereals regularly? Yes _____ No_________ Kinds most often used_____________________ _____ ________ Average number of slices of bread used per day Do you eat many home-baked products? How many servings of butter and/or margarine do you estimate you eat per day _ Do you eat nuts regularly? (a) Yes No (h) Favorite nuts How often do you eats (a) Pie? Once per day? Other ? _____ (b) Cake? Once per day? Other? Twice per week? Once per month? Twice per week? Once per month?_ __ (c) Cookies? Once per day? Other ?__ Twice per week? Once per month?_ (d) Milk puddings? Once per d a y ? „ „ Twice per week? Other (©) Ice Cream? Once per day? Other? (f) Other desserts? Once per month? Twice per w e e k ? _ _ Once per month? — — ---- --- ---- What is your favorite dessert?_^.... ,, ^ How often do you drinks (a) (b) Coffee? _ Servings per & a y „ _ „ _ Servings per week ________ _ (c) (d) Soft drinks?_____ ___ ___ — — (e) Alcoholic beverages?^— ^ What foods not listed above do you dislikes_ ----------- -- -255- Do you have any food allergies? Yes No, If so, what are they What method is used most in. preparing meats? Deep Frying__ Broiling or Roasting. l . Stewing ___ Panbroll Do you wash your meats before cooking? Do you cook vegetables (a) in large amounts of water?Some (b) in small amounts of water?Some How long do Yes_________ you usually cook vegetables? No, All, All^ Until well done? Until tender?. Do you use the stock from canned or home cooked vegetables? Yes No How used (a) With vegetable? Y e s , No In soups or gravies? Yes_______ No, Do you use soda in vegetables? Yes No„ Do you boil such vegetables as potatoes in the skin? Do you commonly add fat for seasoning in cooking? (a) Yes (b) Liberally No , Sparingly_____ Do you take vitamin preparations? Do you take other medication? What kind?. — What kind?. Do you take lascatives?.^^^,.^.^, How How many glasses of water do you drink daily?. What foods do you usually eat for breakfast? Dinner? Supper? What kind?. Peeled?, Do you eat betweengines.! snacks? Regularly?...... What are some typical snacks? _ _ Often? _ __ Do you eat at bedtime?________ Often^____ Seldom _____ Regularly? ,_ ,lju __________. _ What are some typical examples Seldom? -257“ MEDICAL HISTORY Name ____ Date__ Check once the conditions which you have had and give approximate dates Check twice those you now have. Arterio sclerosis Jaundice High blood pressure Arthritis or Gout, Other heart conditions________ Ulcers Measles Colds, frequent. Whooping Cough Pneumonia Diarrhea Migraine headaches, Diphtheria Diabetes Scarlet Fever Smallpox Tuberculosis Gall Bladder disturbances. Typhoid fever Mumps Rheumatic Fever Other (specify) Joint pains __ Have you ever had any surgical operational ___ Explain Have you ever had any broken bones?,, ExplaIn Have you ever been confined to bed for longer than 2 weeks?. If so, why and how long? ._ ^ .. . ----- Do you have a family doctor? When did you last see a dentist?rCTOT_ ^ , When were you last under the care of a doctor? you taking any medications Dentist?^ ^ Is any member of your family now under doctor1 1s care? Why?, Do you ever have: Loss of appetite Nausea or vomiting Cramps Chest pain Fainting spells Shortness of breath Swellings, Boils, Sore mouth. Has either of your parents or any brother or sister had: Tuberculosis Diabetes. Epilepsy Cancer, G o u t __________________ Heart Disease Any significant loss or gain in weight last year?. Approximate range in body weight during adulthood: Have you had children?. How many and what ages?. Menstrual history: Age of menarche Length of cycle. Duration of period. Is medication necessary. Have you completed the menopause? How long did it last? Yes In progress. M„ ^ _ J f e a r s . How long ago was the menopause completed? Years. Did you have? (a) Hot flashes How long? _ _ _ _ _ _ Years Yes No Yes No (b) Nervousness How long? (c) Other Ills _____ Years ___ Were any of these symptoms serious enough to consult a doctor? Yes_ / List the ones that were severe enough to call a doctor v_ _____