Abdominal adiposity and physical fitness are major determinants of the age associated decline in stimulated GH secretion in healthy adults

Growth hormone (GH) secretion is reduced with age in normal subjects. Aging is furthermore associated with a decline in lean body mass and an increase in relative adiposity, and overt obesity is a negative determinant of GH secretion in all age groups. We tested the hypothesis that differences in body composition and physical fitness rather than age determine stimulated GH secretion in healthy adults. Forty-two clinically nonobese adults [22 women and 20 men, mean age 39.4 yr (range 27-59), mean +/- SE body mass index (BMI) = 23.9 +/- 0.5 kg/m2] underwent 2 GH stimulation tests (arginine and clonidine), determination of maximal oxygen consumption (VO2-max), and a number of anthropometric measurements: body mass index (BMI), waist to hip (W/H)-ratio, intraabdominal fat and thigh muscle to fat (M/F)-ratio (computed tomography scan), total body fat, and lean body mass (DEXA scan). Peak GH levels were lower with clonidine [mean +/- SE (micrograms/L): 9.79 +/- 1.29 (arginine) vs. 3.56 +/- 0.57 (clonidine) (P < 0.001)]. Arginine-stimulated GH peak levels correlated negatively with indices of adiposity and age [intraabdominal fat: r = -0.72, P < 0.001; W/H-ratio: r = -0.58, P < 0.001; age: r = -0.54, P < 0.001], and positively with VO2-max [r = 0.60, P < 0.001]. Clonidine-stimulated GH peak correlated negatively with intraabdominal fat [r = -0.60, P < 0.001] and age [r = -0.46, P = 0.008]. Multiple linear regression revealed multicollinearity among several of the independent variables. In all equations abdominal adiposity and physical fitness, rather than age, contributed significantly to predict changes in arginine stimulated GH secretion. Intraabdominal fat was a more important determinant of the clonidine evoked GH response than age. In clinically nonobese, healthy adults relative adiposity, in particular in the abdominal region, is a major negative determinant of stimulated GH secretion, and physical fitness is an important positive predictor. The cause-effect relationship of these observations remains to be elucidated, but our findings may have clinical implications in the diagnosing of GH-deficiency in adults.     

Are anthropometric changes in healthy adults caused by modifications in dietary habits or by aging?

The aim of this work was to investigate to what extent age-dependent anthropometric changes are causally related to changes in dietary habits. In a randomly obtained sample of 246 healthy adults in the age range of 20-90 years from a well-defined agrarian population, the intake of proteins, fat and carbohydrates in males decreases with age (r = -0.65, p < 0.001; r = -0.65, p < 0.001; r = -0.5, p < 0.01, respectively), but in females it remains unaltered (e.g. the mean +/- SD daily protein intake in young adult females is 74 +/- 31 vs. 71 +/- 11 g in individuals over 80); in males it decreases from 140 +/- 34 to 71 +/- 13 g. On the contrary, in both sexes the muscle-mass-related measurements decrease (r = -0.45, p < 0.001; vs. r = -0.41, p < 0.001; mean values of the quotient lean body mass with body length in young adult females and males were 41.9 +/- 4.4 and 52.7 +/- 5.9 vs. 35.0 +/- 3.1 and 43.2 +/- 5.0, respectively, in individuals over 80, p < 0.001 in both sexes). From 35 onwards, the daily urea excretion-as a marker of the protein degradation rate-declines significantly with age, but without a clear correlation to the protein intake (r = 0.38), as occurs during young adulthood (r = 0.63). Furthermore, body fat content tends to increase with age, but the differences are statistically significant only in males of very advanced age (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Body composition and age in African-American and Caucasian women: relationship to plasma leptin levels

Leptin is a recently isolated peptide hormone released from adipocytes that has been postulated to play a role in appetite regulation and energy metabolism. Aging affects both food intake and body composition. Body composition is also affected by ethnicity. We have evaluated the relationships between serum leptin levels, age, body composition (by dual-energy x-ray absorptiometry), and hormonal parameters in a cross-sectional study of 94 women, 53 African-American (AAF) and 41 Caucasian (CF). Our hypotheses were as follows: (1) changes in body composition would be related to age in a sinusoidal pattern, (2) changes in serum leptin would parallel changes in body fat, (3) serum leptin levels would be influenced by body fat distribution, and (4) serum leptin would be related to serum concentrations of sex hormones. Serum leptin paralleled changes in body fat and body mass index (BMI) with age. In the entire group, serum leptin correlated closely with measures of body fat, including BMI and total fat mass, and there was no difference in leptin levels between the two ethnic groups. In simple regression analysis, serum leptin was related to both serum estradiol and testosterone. The relationship between serum leptin and trunk fat was linear in both groups, but significantly different in AAF and CF (P = .014). Serum leptin was associated with the trunk to lower-extremity fat ratio in CF (r = .67, P = .001) but not in AAF. Body fat was increased with advancing age until about 65 years and then declined. Measures of lean body mass declined linearly with age in the entire group, as well as both subgroups. In the entire group, total lean body mass and lean body mass corrected for BMI (lean body mass/BMI) were inversely related to age. In subjects aged less than 60 years AAF were stronger (P < .05) and had both a larger BMI and fat mass (P < .05) than CF. However, the patterns of age-related changes in fat body mass, lean body mass, and BMI were similar in both groups. In the entire group, multiple regression analysis indicated that the age, free thyroxine index (FTI), and leptin concentration were predictors of the body composition and distribution of trunk to lower-body fat. These observations indicate that there is a sinusoidal relationship between body fat and age, with a decline in body fat in extreme old age in both AAF and CF, and that serum leptin concentrations are more closely related to body fat and BMI than to age or ethnicity.     

Body composition in normal subjects: relation to lipid and glucose variables

OBJECTIVE: To describe sex- and age-dependent values of total and regional body composition as determined by dual-energy X-ray absorptiometry (DXA) in normal subjects, and furthermore to relate body composition measurements to blood lipids, glucose and insulin concentrations. DESIGN: A cross-sectional study. SUBJECTS: 173 (84 male and 89 female) healthy subjects, BMI < 30 kg/m2. MEASUREMENTS: Body composition parameters including data on total bone mineral content (TBMC), total bone mineral density (TBMD), lean body soft tissue mass (LTM), total and regional fat mass (FM) were estimated in all subjects. In 87 of the subjects fasting blood glucose, S-insulin and lipid profile were measured. RESULTS: The study population was for each sex divided into five decades for which results on body composition and blood lipids are presented. Body weight increased 2 kg per age decade, representing a significant increase in both total FM and relative FM (FM%BW) with age, and in males a central accumulation of FM. LTM decreased significantly in males but not in females, whereas TBMC and TBMD remained constant in males, but decreased in females. A significant correlation between relative FM and S-cholesterol, S-triglyceride, and in males S-insulin was found. CONCLUSION: The present study gives coherent data on bone mineral content, lean body soft tissue mass total and regional fat mass for 173 healthy subjects with a BMI below 30 kg/m2. Total body fat mass increases, and lean mass decreases with age. In males a simultaneous central accumulation of fat mass is observed. The well-known relationship between central obesity and lipids is confirmed even in non-obese subjects.     

Sagittal abdominal diameter as a practical predictor of visceral fat

OBJECTIVE: To evaluate the relationships between the supine sagittal abdominal diameter (SAD) and visceral fat, as well as to evaluate intra- and inter-observer reliability of sagittal diameter measurement. PATIENTS: Twenty-eight women ranging in age from 27-78 y with a body mass index (BMI) ranging from 16.9-48.1 kg/m2 and 23 men ranging in age from 32-75 y with BMI ranging from 20-41.6 kg/m2. MEASUREMENT: Body fat distribution was measured by waist circumference, waist to hip ratio (WHR), SAD, anthropometrically assessed and a single slice of computed tomography (CT) at the L4-L5 level. RESULTS: In both genders, a significant association was found between visceral adipose tissue (AT) and SAD, as evaluated by CT (women r = 0.80; men r = 0.83, P < 0.001), and SAD by anthropometry (women r = 0.76; men r = 0.82, P < 0.001), as well as between visceral AT and waist circumference (women r = 0.76, men r = 0.86, P < 0.001) and WHR (women r = 0.57, P < 0.01, men r = 0.80, P < 0.001). A significant association was also found between subcutaneous AT and SAD by anthropometry (women r = 0.79, men r = 0.74, P < 0.001). After adjusting for BMI, the association between subcutaneous AT and SAD was no longer significant in men and only moderately significant in women (r = 0.42, P < 0.05), while the association between visceral AT and SAD by anthropometry remained significant in both genders (women r = 0.63, P < 0.001; men r = 0.66, P < 0.001). When the subjects were divided into two groups according to BMI (lean to moderately overweight women with BMI < 28 and men with BMI < 30 and obese women with BMI > 28 and men with BMI > 30) we found that the relationships between SAD by anthropometry, as well as SAD by CT and visceral AT, were higher in lean to moderately overweight subjects than in those who were obese. High inter-observer correlation was found concerning SAD measurement (r = 0.99, P < 0.001). Intra- and inter-observer precision as evaluated by coefficient of variation and intraclass correlation coefficient for SAD measurement was very high. CONCLUSION: Our study shows the usefulness of SAD by anthropometry to predict visceral fat and its very high inter- and intra-observer precision.     

Climatic influences on human body size and proportions: ecological adaptations and secular trends

This study reevaluates the long-standing observation that human morphology varies with climate. Data on body mass, the body mass index [BMI; mass (kg)/stature (m)2], the surface area/body mass ratio, and relative sitting height (RSH; sitting height/stature) were obtained for 223 male samples and 195 female samples derived from studies published since D.F. Roberts' landmark paper "Body weight, race, and climate" in 1953 (Am. J. Phys. Anthropol. 11:533-558). Current analyses indicate that body mass varies inversely with mean annual temperature in males (r=-0.27, P < 0.001) and females (r=-0.28, P < 0.001), as does the BMI (males: r=-0.22, P=0.001; females: r=-0.30, P < 0.001). The surface area/body mass ratio is positively correlated with temperature in both sexes (males: r=0.29, P < 0.001; females: r=0.34, P < 0.001), whereas the relationship between RSH and temperature is negative (males: r=-0.37, P < 0.001; females: r=-0.46, P < 0.001). These results are consistent with previous work showing that humans follow the ecological rules of Bergmann and Allen. However, the slope of the best-fit regressions between measures of body mass (i.e., mass, BMI, and surface area/mass) and temperature are more modest than those presented by Roberts. These differences appear to be attributable to secular trends in mass, particularly among tropical populations. Body mass and the BMI have increased over the last 40 years, whereas the surface area/body mass ratio has decreased. These findings indicate that, although climatic factors continue to be significant correlates of world-wide variation in human body size and morphology, differential changes in nutrition among tropical, developing world populations have moderated their influence.     

The reliability of upper limb anthropometry in older Chinese people

OBJECTIVE: To evaluate the validity of the Durnin-Womersley equations and to derive our local predictive equations for body fat from upper limb skinfold thicknesses in older Chinese people in Hong Kong. To evaluate the validity of mid-arm circumference and corrected arm muscle area in predicting lean tissue mass in the same population. DESIGN: Comparison of fat percentages predicted by Durnin-Womersley (D-W) equations with those estimated by Dual energy X ray absorptiometry (DXA). Predictive equations derived from regression between upper limb skinfold thicknesses and fat percentages estimated by DXA were similarly evaluated in internal and external validation groups. Mid-arm circumference (MAC) and corrected arm muscle area (CAMA) were correlated with the limb lean tissue mass, body lean tissue mass and fat percentage. SUBJECTS: 354 female and 263 male, apparently well, community dwelling subjects, aged 69-82 y; of which 40 subjects of each sex were randomly selected from the study population for internal validation of the local predictive equations; 60 female and 33 male hospital medical outpatients, aged 61-87 y, were recruited for external validation. MEASUREMENTS: Triceps and biceps skinfold thicknesses, mid-arm circumference, body mass index, fat percentages, limb and whole body lean tissue masses estimated by Hologic QDR-2000 bone densitometer. RESULTS: Fat percentages calculated by D-W equations were significantly different from those estimated by DXA (average difference -2.4 (s.d. 4.8)% and +2.1 (5.2)% in females and males respectively). The corresponding differences for our local predictive equations were not significant (-0.9 (4.7)% and -0.5 (5.0)% in females and males respectively). There was a trend of under-estimation of body fat with increasing fatness. In the hospital medical outpatients, there was a significant difference between fat percentages predicted by our equation and those by DXA in female (-2.9(5.3)%), but not in male (+0.3(4.3)%) subjects. In males, MAC correlated with limb and body lean tissue masses as well as with fat percentage (r = 0.60, 0.68, 0.65 respectively). CAMA correlated similarly well with lean tissue masses but was more independent of fat percentage (r = 0.61, 0.65, 0.44 respectively). In females, both MAC and CAMA correlated poorly with limb and body lean tissue masses. Moreover, MAC correlated well with fat percentage (r = 0.80). CONCLUSION: Upper limb skinfold thicknesses measurement is a valid means of predicting body fat in older Chinese people. Local predictive equations were more reliable that D-W equations. They were, however, subject to errors at the extreme ends of body fatness and in the presence of disease. In older females, MAC and CAMA were not reliable in predicting lean tissue mass, but MAC could be used to predict fat percentages. In older males, CAMA was more reliable than MAC in predicting lean tissue mass.     

Disruption of the relationship between fat content and leptin levels with aging in humans

Leptin released from adipose tissue is believed to participate in a negative feedback loop regulating appetite, and malfunction of this mechanism could lead to obesity. We measured plasma leptin and body composition (dual energy x-ray absorptiometry) in 70 healthy subjects, divided into 3 age groups (young, 25 +/- 1 yr; middle-aged, 53 +/- 1 yr; old, 70 +/- 1 yr), while on a 5-day weight-maintaining diet. Pairwise correlations were assessed using product-moment correlation, and regression analysis was used to evaluate relationships between leptin and other variables. Leptin concentrations and relative body fat content were correlated in young females (r = 0.71; P = 0.009) and in young males (r = 0.76; P = 0.007), but not in the combined middle-aged and elderly groups (r = 0.19; P = 0.36 and r = 0.19; P = 0.38 in females and males, respectively). Regression analysis showed a clear correlation between circulating leptin and relative fat mass in the young subjects (P = 0.0001), but not in the older subjects (P = 0.199). We conclude that body fat content in young subjects correlates with plasma leptin in both genders, whereas this relationship is disrupted in elderly subjects, thus possibly contributing to the obesity occurring with age.     

Protection of both auditory hair cells and auditory neurons from cisplatin induced damage

Knowledge about body composition is important in metabolic and nutritional studies. In this cross-sectional study the body composition of 403 healthy white Dutch children and adolescents was evaluated by using dual-energy X-ray absorptiometry (DXA). Possible determinants of body composition were analyzed. In 85 subjects the results of bioelectrical impedance analysis (BIA) were compared with DXA. Fat mass, lean tissue mass, and bone mineral content were greater in older boys and girls. Percentage body fat was greater in older girls but not in boys and it was higher in girls than in boys at all ages. From the age of 14 y boys had higher lean tissue mass and bone mineral content than girls. Tanner stage had a significant relation with body composition in both sexes. Percentage body fat was lower in boys in stage 4 than in stage 3 and was higher in consecutive Tanner stages in girls. After adjustment for age, Tanner stage was significantly positively related to lean tissue mass and bone mineral content in boys and girls and to percentage body fat and fat mass in girls. The profession of the parents and the education of the father had a significant negative correlation with percentage body fat and fat mass in girls (P < 0.01). Physical activity was related to lean tissue mass (P = 0.001) but not to fat mass in boys after adjustment for age. A high correlation and a small difference was found between lean body mass by BIA and lean tissue mass by DXA. Body composition in healthy Dutch children and adolescents is related to age, sex, Tanner stage, socioeconomic status, and physical activity.     

Diabetes during pregnancy does not alter whole body bone mineral content in infants

A previous study using single photon absorptiometry has reported low bone mineral density of the radius in infants of diabetic mothers. The aim of this study was to assess by dual x-ray absorptiometry the whole body bone mineral content (WbBMC) and the body composition of 40 infants of diabetic mothers at birth (mean gestational age +/- SD, 37.5 +/- 1.3 weeks; mean birth weight +/- SD, 3815 +/- 641 g). WbBMC was not correlated with gestational age, but was well correlated with birth weight (r = 0.73; P = 0.0001) and also with fat mass (r = 0.87; P = 0.0001) and lean mass (r = 0.42; P = 0.008). The z-scores +/- SD adjusted for weight for WbBMC and fat mass were significantly increased (1.3 +/- 0.9 and 2.6 +/- 1.3, respectively (P < 0.0001), but were not significantly influenced either by in utero growth or by the type of the diabetes mellitus of the mother. Bone mineralization and fat mass studied by whole body dual x-ray absorptiometry are increased at birth in these infants compared with reference curves.     

Heart failure and atrial fibrillation: current concepts and controversies

OBJECTIVE: Leptin is the product of ob gene shown to regulate body fat in mice. It is produced by human adipose tissue as well, but its physiological functions in man are not known. We explored if there is a relationship in obese humans with serum leptin and energy and fuel metabolism. DESIGN: Cross-sectional study including 45 obese (10 men, 35 women; age and body mass index: 42 +/- 7 y and 35.1 +/- 3.6 kg/m2, respectively). MEASUREMENTS: Food intake by a four-day-food record, blood samples for serum leptin concentrations and resting energy expenditure by indirect calorimetry. RESULTS: Leptin concentrations showed an inverse association (adjusted for fat mass, age and sex) with resting energy expenditure, respiratory quotient and carbohydrate oxidation rate (r = -0.324, P < 0.05; r = -0.420, P < 0.01; r = 0.478, P = < 0.01, respectively), and interestingly, also with dietary fat intake (unadjusted r = -0.30, P < 0.05). Especially, leptin concentrations were elevated in those with low resting energy expenditure and respiratory quotient (below the median). CONCLUSION: Serum leptin concentrations in obese subjects showed an inverse association with resting energy expenditure, respiratory quotient and carbohydrate oxidation rate. The physiological significance of these associations is unclear at the moment but could indicate that obese subjects show resistance to the actions of leptin also outside the brain in terms of regulating metabolic rate and fuel metabolism.     

Genetic influences on plasma catecholamines in human twins

We examined the relative genetic and environmental influences on the variability in plasma epinephrine, norepinephrine, and dopamine levels in 109 twin pairs. Epinephrine levels were lower in females (P = 0.048). The norepinephrine concentration increased with age (r = 0.40; P < 0.001). Blood pressure (BP) was not associated with epinephrine levels in either sex or with norepinephrine levels in females. In males, there was a positive association between norepinephrine concentration and diastolic BP (r = 0.31; P = 0.020). A negative association between dopamine levels and systolic and diastolic BP in females (r = -0.22; P = 0.014 and r = -0.20; P = 0.027, respectively) was not maintained after accounting for age, body mass index, and sex. Using path analysis and maximum likelihood model fitting, genetic, unique environment, and age effects contributed 57% (P < or = 0.001), 27% (P < or = 0.001), and 16% (P < or = 0.001) to the variability in norepinephrine, respectively. Genetic effects explained 64% (P < 0.1) and 74% (P < 0.1) of the variability in epinephrine concentrations in females and males, respectively. Unique environmental influences explained the remainder. Genetic and unique environmental effects explained 72% (P < 0.01) and 28% (P < or = 0.001) of the variability in dopamine levels. These results indicate a substantial genetic influence on plasma catecholamine levels. Although consistent associations between plasma catecholamines and BP were not evident in this study, the observed genetic influence on circulating catecholamines may be relevant to the potential role of the sympathetic nervous system in the early stages of essential hypertension.     

Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women

OBJECTIVE: To compare the effects on body composition and body weight of tibolone vs two different sequential oral or transdermal oestrogen-progestogen hormone replacement therapies versus no therapy. PATIENTS AND METHODS: One hundred postmenopausal women were assigned to a control group (n = 26), or randomized to 1) tibolone (TIB) 2.5 mg/day (n = 28), 2) oral oestradiol 2 mg/day (PO) plus sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 26), or 3) transdermal oestradiol patch (TTS) releasing 50 micrograms/day plus oral sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 20). Body composition was measured at the base-line and every 6 months for 2 years by DXA (Hologic QDR 1000 W). RESULTS: Total body fat mass increased (P < 0.05) in controls (+3.6 +/- 1.5%) and in TTS treated (+4.7 +/- 2.2%), but not in PO (-1.2 +/- 2.4%) and TIB (-1.6 +/- 2.2%) treated subjects. This increase in total fat mass in controls and TTS treated women was mostly due to an increase in fat mass of the trunk (P < 0.05), but not legs. As a result, a redistribution of body fat to the trunk occurred in controls, TTS and TIB, but not in PO treated women (P < 0.05). Total lean body mass decreased (P < 0.02) in controls (-1.7 +/- 0.7%) and PO (-1.4 +/- 0.6%) but not in TTS (+0.3 +/- 0.8%) and TIB (+0.4 +/- 0.5%) treated subjects. CONCLUSIONS: The menopause is associated with an increase in total body fat and a decline in lean body mass. Oral oestradiol/dydrogesterone and tibolone prevent total body fat changes, whereas transdermal oestradiol/oral dydrogesterone and tibolone prevent the lean mass changes. Furthermore, oral oestradiol/dydrogesterone prevents the shift to a central, android fat distribution.     

A cross-sectional analysis on relationships between maximum oxygen uptake and risk factors for cardiovascular diseases

We examined the relationships between maximum oxygen uptake (Vo2max) and cardiovascular risk factors including age (year), systolic blood pressure (mmHg), diastolic blood pressure (mmHg), serum total cholesterol level (mg/dl), serum high-density lipoprotein level (mg/dl), serum triglyceride level (mg/dl), blood glucose level (mg/dl), serum uric acid level (mg/dl), body fat (%bw), Body Mass Index (BMI), alcohol (points/day), cigarettes (/day), and physical activity (METs.exercise time/30 days). The alcohol point was defined as follows: beer 633ml = a glass of whiskey and water - sake 180ml = 1 point, and totaled at 30 days. The subjects of our study were 162 males (aged 40.6 +/- 13.1) and 133 females (aged 41.3 +/- 11.1) who underwent medical and physical examinations at the Fukui Industrial Health Center from April, 1991 to June, 1992. As a result of simple correlation analysis in males, Vo2max had significantly negative correlations with age (r = -0.223, p < 0.01), systolic blood pressure (r = -0.228, p < 0.01), diastolic blood pressure (r = -0.239, p < 0.01), or serum triglyceride level (r = -0.258, p < 0.001), serum uric acid level (p < 0.05), body fat (r = -0.230, p < 0.01), and BMI (r = -0.312, p < 0.001), and was positively correlated with physical activity (r = -0.249, p < 0.01). On the other hand, in females, age (r = -0.224, p < 0.01), systolic blood pressure (r = -0.222, p < 0.01), diastolic blood pressure (r = -0.267, p < 0.01), serum triglyceride level (r = -0.261, p < 0.001), body fat (r = -0.280, p < 0.01), and BMI (r = -302, p < 0.001), had significantly negative correlations with VO2max. However, partial correlations were tested after controlling body fat, BMI, cigarette, alcohol, physical activity, and age, none of the factors correlated with VO2max significantly. These findings suggest that the risk factors for cardiovascular diseases are related to VO2max, and the life style has an influence on these correlations. Thus, VO2max may be a comprehensive indicator for health promotion among the working population. Furthermore a longitudinal study is required to determine whether the increase in VO2max is related to the improvement in the risk of cardiovascular diseases.     

What makes a life good?

OBJECTIVE: The objective of this study was to evaluate the longitudinal changes in energy expenditure and body composition in relationship to alterations in carbohydrate metabolism in women with normal and abnormal glucose metabolism. We hypothesized that women with decreased insulin sensitivity before conception would have less fat accretion and smaller increases in energy expenditure. STUDY DESIGN: Six women with normal glucose tolerance and 10 women with abnormal glucose tolerance were evaluated before conception, and in early (12 to 14 weeks) and late (34 to 36 weeks) gestation. Body composition was estimated by hydrodensitometry, resting energy expenditure, and glucose and fat metabolism by indirect calorimetry, endogenous glucose production by infusion of [6-6 2H2] glucose, and insulin sensitivity using a hyperinsulinemic-euglycemic clamp (40 mU/m2/min). RESULTS: There was a smaller increase in fat mass (1.3 kg [P = .04]) in early pregnancy in women with abnormal glucose tolerance before pregnancy. Indirect calorimetry measured gestational age-related increases in basal oxygen utilization, with or without correction for fat-free mass (VO2, P = .002), resting energy expenditure (expressed in kilocalories, P = .0001), and carbohydrate oxidation (P = .0003). The insulin-mediated elevation in VO2 increased in later gestation VO2 (P = .005), as did resting energy expenditure (P = .0001) and fat oxidation (P = 0.0001). However, there was a decrease in respiratory quotient (P = .0001), carbohydrate oxidation (P = .002), and nonoxidative carbohydrate metabolism (P = .0001) with advancing gestation during insulin infusion. In early pregnancy, changes in fat mass correlated inversely with changes in insulin sensitivity (r= -0.52, P = .04) and changes in basal VO2 correlated inversely with decreases in basal endogenous glucose production (r = -0.74, P = .01). CONCLUSION: In early gestation, the changes in maternal fat mass and basal oxygen consumption are inversely related to the changes in insulin sensitivity. This response in lean women with decreased insulin sensitivity before conception may have survival value by providing a larger amount of available substrate to meet fetoplacental needs during gestation.     

The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin

Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass with age, is an important age-related cause of frailty and loss of independence in the elderly. Because the decline in BCM with age parallels a decline in GH secretion from young adulthood to old age, loss of GH secretion has been considered an important contributory cause of sarcopenia in the elderly. To test this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD age, 66.9 +/- 7.8 yr), 24-h GH concentrations and secretory kinetics were correlated with BCM (measured by whole body counting of 40K) and percent body fat (measured by dual energy x-ray absorptiometry or neutron inelastic scattering). Serum leptin levels were determined as a measure of adipocyte mass. Contrary to prediction, GH secretion was lower in women with higher BCM (r = 0.50; P < 0.05), whereas their mean fat mass was higher (r = 0.51, P < 0.05). These data indicate that sarcopenia in postmenopausal women is not associated with reduced GH secretion and is inversely correlated with fat mass. Serum leptin levels were inversely associated with GH secretion (r = -0.67; P < 0.006). Although a causal relationship has not been demonstrated, these data suggest that leptin could modulate GH secretion through its action on the aging hypothalamic-pituitary axis, or that GH regulates leptin secretion.     

Fat distribution and hemostatic measures in obese children

We examined the relation of general and visceral adiposity to plasma hemostatic factors [fibrinogen, D-dimer, and plasminogen activator inhibitor 1 (PAI-1)] in obese boys and girls 7-11 y of age (n = 41). Boys had significantly greater fibrinogen and D-dimer concentrations than girls (P < 0.05). whereas blacks had significantly greater fibrinogen and D-dimer concentrations than whites (P < 0.05). Univariate analyses revealed that fibrinogen was positively associated with percentage body fat (%BF) (r = 0.42, P < 0.01), subcutaneous abdominal adipose tissue (SAAT) (r = 0.40, P < 0.01), total fat mass (r = 0.42, P < 0.01), and body mass index (r = 0.41, P < 0.01). PAI-1 was positively associated with visceral adipose tissue (VAT) (r = 0.49, P < 0.01), SAAT (r = 0.32, P < 0.05), fat-free mass (r = 0.50, P < 0.01), and insulin (r = 0.61, P < 0.001). D-Dimer was positively associated with %BF (r = 0.40, P < 0.01), SAAT (r = 0.37, P < 0.05), total fat mass (r = 0.40, P < 0.01), and body mass index (r = 0.43, P < 0.01). Multiple regression analysis revealed that for fibrinogen, sex and higher %BF explained significant independent portions of the variance. For PAI-1, higher amounts of VAT and fat-free mass were significant predictors. For D-dimer, ethnicity was a significant predictor. These results suggest that general adiposity and VAT may play a role in regulating plasma hemostatic factors in obese children. Even early in childhood, adiposity is associated with unfavorable concentrations of hemostatic factors that are in turn implicated in cardiovascular morbidity and mortality later in life.     

Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans

Stimulation of beta3-adrenoceptors by selective agonists improves insulin action and stimulates energy metabolism in various rodent models of obesity and type 2 diabetes. Whether selective beta3-adrenoceptor stimulation exerts metabolic actions in humans remains to be proven. The effects of a highly selective beta3-adrenoceptor agonist on insulin action, energy metabolism, and body composition were assessed in 14 healthy young lean male volunteers (age 22.5 +/- 3.3 years, 15 +/- 5% body fat [mean +/- SD]) randomly assigned to 8 weeks of treatment with either 1,500 mg/day of CL 316,243 (n = 10) or placebo (n = 4). Insulin-mediated glucose disposal (IMGD), nonoxidative glucose disposal (NOGD), oxidative glucose disposal (OGD) (indirect calorimetry), and splanchnic glucose output (SGO; beta3-[H3]glucose) were determined during a 100-min hyperinsulinemic-euglycemic glucose clamp (40 mU x m(-2) x min(-1)) before and after 4 and 8 weeks of treatment. The 24-h energy expenditure (24-EE), 24-h respiratory quotient (24-RQ), and the oxidation rates of fat and carbohydrate were determined in a respiratory chamber before and after 8 weeks. After 4 weeks, treatment with CL 316,243 increased IMGD (+45%, P < 0.01) in a plasma concentration-dependent manner (r = 0.76, P < 0.02). This effect was due to an 82% increase in NOGD (P < 0.01), while OGD and SGO remained unchanged. The effects on insulin action were markedly diminished after 8 weeks; this was significantly related to an unexpected decline in the plasma concentrations of CL 316,243 (-36%, P = 0.08). At this time, 24-RQ was lowered (P < 0.001), corresponding to a 23% increase in fat oxidation (P < 0.01) and a 17% decrease in carbohydrate oxidation (P = 0.05). The 24-EE after 8 weeks did not differ from baseline, and there was no change in body weight or body composition. Plasma concentrations of glucose, insulin, and leptin were unaffected by treatment, while free fatty acid concentrations increased by 41% (P < 0.05), again linearly with the achieved plasma concentration of CL 316,243 (r = 0.67, P < 0.05). Treatment with CL 316,243 had no effect on heart rate or blood pressure and caused no cases of tremors. We conclude that treatment of lean male subjects with CL 316,243 increases insulin action and fat oxidation, both in a plasma concentration-dependent manner. This is the first study to demonstrate unequivocal metabolic effects of a highly selective beta3-adrenoceptor agonist in humans.     

A dual-luciferase reporter system for studying recoding signals

OBJECTIVE: Growth hormone status is an important determinant of serum IGF-I but it is well known that hypopituitary adults with pronounced GH-deficiency (GHDA) may exhibit normal IGF-I levels. To elucidate possible causes of this apparent paradox we compared the significance of putative IGF-I predictors in GHDA and normal subjects. DESIGN: A cross-sectional study. SUBJECTS: Twenty-seven GHDA (9 females, 18 males, mean +/- SE age 44 +/- 1 years) and 27 healthy control subjects (9 females, 18 males, mean +/- SE age 43 +/- 2 years). RESULTS: Serum IGF-I and IGFBP-3 were significantly lower in GHDAs, but a considerable overlap existed (IGF-I (microgram/l) 87 +/- 12 (GHDA) vs 177 +/- 10 (Control) (P < 0.001)). In both Controls and GHDA, IGF-I was higher in males than females (Control: 196 +/- 12 vs 138 +/- (P = 0.004); GHDA: 97 +/- 16 vs 56 +/- 11 (P = 0.05)). In GHDA, males on testosterone substitution had the highest IGF-I concentrations. The molar IGF-I:IGFBP-3 ratio was significantly lower in GHDAs (0.18 +/- 0.01 vs 0.23 +/- 0.02 (P = 0.002)). IGFBP-1 (microgram/l) was significantly elevated in GHDAs (6.28 +/- 1.11 vs 3.07 +/- 0.32 (P < 0.001)) despite comparable fasting insulin levels. Percentage total body fat (TBF, DEXA, waist/hip ratio, and intra-abdominal fat (CT) were all elevated in GHDAs. IGF-I correlated positively with lean body mass (DEXA) and negatively with TBF and IGFBP-1 in both groups. IGF-I correlated negatively with age in CON but not in GHDAs, whereas IGF-I correlated positively with IGFBP-3 only in GHDAs. Multiple regression analysis revealed that age and IGFBP-1 were the only significant predictors of IGF-I in CON, whereas IGFBP-3 and, to a lesser extent TBF, were the only independent predictors of IGF-I in GHDAs. Neither peak stimulated GH, nor physical fitness contributed in any equations in the two groups. CONCLUSIONS: 1) IGF-I levels are regulated by several variables in addition to GH status 2) age per se is an independent negative determinant in healthy subjects but not in GHDA 3) it is probable that some cases of paradoxically high IGF-I levels in GHDA are secondary to inappropriately elevated IGFBP-3 levels. 4) in mid-adulthood males have higher IGF-I levels than females and it is likely that testosterone directly stimulates IGF-I. The influence of gender and sex steroids must therefore be accounted for when comparing IGF-I levels between hypopituitary and healthy subjects.     

Body composition in children receiving recombinant human growth hormone after renal transplantation

BACKGROUND: Recombinant human growth hormone (rhGH) is an anabolic hormone promoting protein synthesis in various tissues. Therefore, changes in body composition may be expected during rhGH treatment. METHODS: We studied changes in body composition during two years of rhGH treatment in 21 children after at least one year with a functioning renal transplant. The mean +/- SD age was 12.9+/-2.5 years at the start of rhGH therapy. A whole body, dual energy X-ray absorptiometry (DEXA) exam was performed before the initiation of rhGH therapy (T0), and was repeated at one and two year intervals after initiation of the therapy (T1 and T2, respectively). RESULTS: Lean body mass increased by a median of 0.48 SDS during the first year of treatment (P = 0.022), and the median increase during two years of therapy was 0.36 SDS (P = 0.061). On the contrary, the median fat body mass decreased by 2.17 SDS during the T0 to T1 period (P = 0.04) and by 1.99 SDS during the T0 to T2 period (P = 0.055). The index for fat body mass/lean body mass (FBM/LBM) decreased by a median of 5.3% during T0 to T1 (P < 0.001), however, a slower but still significant decrease by a median of 4.2% was noted at T2 (P < 0.05). Bone mass content did not change significantly during rhGH treatment. The medians in caloric and protein intakes were stable during rhGH treatment. CONCLUSION: A significant increase of lean body mass and a decrease of fat body mass was noted during rhGH therapy in children after renal transplantation.