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Biomedical subjects

B A Gower

Publications and source records attributed to B A Gower.

At least 19 recordsLinked to original sources

Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when compared with the minimal model.

OBJECTIVE: To compare insulin sensitivity (Si) from a frequently sampled intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses with surrogate measures of insulin sensitivity and resistance and to compare features of the metabolic syndrome between Caucasians and Indian Asians living in the UK. SUBJECTS: In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si of 2.85+/-0.37. MEASUREMENTS: Si was determined from an FSIGT with subsequent minimal model analysis. The concentrations of insulin, glucose and nonesterified fatty acids (NEFA) were analysed in fasting plasma and used to calculate surrogate measure of insulin sensitivity (quantitative insulin sensitivity check index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index, fasting insulin, insulin-to-glucose ratio). Plasma concentrations of triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and low density cholesterol, (LDL-C) were also measured in the fasted state. Anthropometric measurements were conducted to determine body-fat distribution. RESULTS: Correlation analysis identified the strongest relationship between Si and the revised QUICKI (r=0.67; P=0.000). Significant associations were also observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009), FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive (Si) than the Caucasian group (P=0.02). CONCLUSION: The revised QUICKI demonstrated a statistically strong relationship with the minimal model. However, it was unable to differentiate between insulin-sensitive and -resistant groups in this study. Future larger studies in population groups with varying degrees of insulin sensitivity are recommended to investigate the general applicability of the revised QUICKI surrogate technique.

Adult↗

Anti-lipolytic effects of insulin in African American and white prepubertal boys.

OBJECTIVE: Relative to whites, African Americans have lower circulating triglycerides (TG) and greater highdensity lipoprotein cholesterol. The metabolic basis for this difference is not known. This study was conducted to test the hypothesis that insulin-induced suppression of free fatty acids (FFA) results in lower serum TG in African American versus white prepubertal children. RESEARCH METHODS AND PROCEDURES: Insulin, FFA, and TG were determined at baseline and during a frequently sampled, intravenous glucose tolerance test in eight African American and eight white prepubertal males pair-matched for whole-body insulin sensitivity. RESULTS: Baseline TG was lower in African Americans (0.43 +/- 0.10 vs. 0.79 +/- 0.37 mM/L; mean +/- SD; p < 0.01). African Americans had higher peak insulin (218 +/- 102 vs. 100 +/- 30 pM/L; mean +/- SD; p < 0.01) and a greater acute insulin response (9282 +/- 4272 vs. 4230 +/- 1326 pM/L x 10 minutes; mean +/- SD; p < 0.05). FFA and TG values determined at the FFA nadir were lower in African Americans (0.26 +/- 0.02 vs. 0.30 +/- 0.03 mEq/L; mean +/- SD; p < 0.01 for FFA nadir and 0.49 +/- 0.07 vs. 0.77 +/- 0.33 mM/L; mean +/- SD; p < 0.05 for TG). Among all subjects, FFA nadir was correlated with peak insulin (r = -0.54; p < 0.05). After adjusting for FFA nadir, neither baseline nor postchallenge TG differed with ethnicity (p = 0.073 and 0.192, respectively). The ethnic difference in FFA nadir disappeared after adjusting for peak insulin (p = 0.073). DISCUSSION: These data suggest that hyperinsulinemiainduced suppression of FFA among African Americans is a determinant of lower TG in this group.

Arteriosclerosis↗

Defining health-related obesity in prepubertal children.

OBJECTIVE: The purpose of this study was to develop percentage of fat and waist circumference cut-points in prepubertal children with the intention of defining obesity associated with cardiovascular disease (CVD) risk. RESEARCH METHODS AND PROCEDURES: A cross-sectional analysis of 87 prepubertal children aged 4 to 11 years was used. Percentage of body fat was determined by DXA. Waist circumference was measured to the nearest millimeter. Receiver Operating Characteristic analyses of percentage of fat and waist circumference were used to develop cut-points for individuals with adverse levels of CVD risk factors. RESULTS: The risk factors selected for analyses (i.e., fasting insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol/high-density lipoprotein cholesterol) were significantly related to percentage of body fat and waist circumference. Likelihood ratios were used to identify percentage of fat and waist circumference cut-points associated with adverse cardiovascular risk profiles. Two cut-points, an upper cut-point of 33% body fat and a lower cut-point of 20% body fat, were derived. Waist circumference cut-points indicative of adverse and normal risk-factor profiles were 71 cm and 61 cm, respectively. DISCUSSION: The data indicate that children with > or =33% body fat and children with a waist circumference > or =71 cm were more likely to possess an adverse CVD risk-factor profile than a normal risk-factor profile. The likelihood of children with < 20% body fat or a waist circumference < 61 cm possessing an adverse CVD risk-factor profile as opposed to a normal risk-factor profile was small. The cut-points describe an adequate health-related definition of childhood obesity.

Absorptiometry, Photon↗

Effect of scalp and facial hair on air displacement plethysmography estimates of percentage of body fat.

OBJECTIVE: The objective of this study was to determine the effect of body hair (scalp and facial) on air displacement plethysmography (BOD POD) estimates of percentage of body fat. RESEARCH METHODS AND PROCEDURES: A total of 25 men (31.4 +/- 8.0 years, 83.4 +/- 12.2 kg, 181.8 +/- 6.9 cm) agreed to grow a beard for 3 weeks to participate in the study. Total body density (g/cm(3)) and percentage of body fat were evaluated by BOD POD. To observe the effect of trapped isothermal air in body hair, BOD POD measures were performed in four conditions: criterion method (the beard was shaven and a swimcap was worn), facial hair and swimcap, facial hair and no swimcap, and no facial hair and no swimcap(.) RESULTS: The presence of only a beard (facial hair and swimcap) resulted in a significant underestimation of percentage of body fat (16.2%, 1.0618 g/cm(3)) vs. the criterion method (17.1%, 1.0597 g/cm(3), p < 0.001). The effect of scalp hair (no swim cap worn) resulted in a significant underestimation in percentage of body fat relative to the criterion method, either with facial hair (facial hair and no swimcap; 14.8%, 1.0649 g/cm(3)) or without facial hair (no facial hair and no swimcap; 14.8%, 1.0650 g/cm(3), p < 0.001 for both). DISCUSSION: A significant underestimation of percentage of body fat was observed with the presence of facial hair ( approximately 1%) and scalp hair ( approximately 2.3%). This underestimation in percentage of body fat may be caused by the effect of trapped isothermal air in body hair on body-volume estimates. Thus, excess facial hair should be kept to a minimum and a swimcap should be worn at all times to ensure accurate estimates of body fat when using the BOD POD.

Adipose Tissue↗

Influence of total vs. visceral fat on insulin action and secretion in African American and white children.

OBJECTIVE: To examine whether total body fat (FAT) in general or visceral fat (VFAT) in particular is associated with greater metabolic risk in white and African American children. RESEARCH METHODS AND PROCEDURES: A total of 68 white and 51 African American children had measures of insulin sensitivity (Si) and acute insulin response (AIR) by a frequently sampled intravenous glucose tolerance test, total body fat by DXA and abdominal fat distribution (visceral vs. subcutaneous) by computed tomography. The influence of FAT and VFAT on insulin parameters were examined by comparing subgroups of children with high or low FAT vs. high or low VFAT and by multiple regression analysis. RESULTS: In whites, fasting insulin, Si, and AIR were significantly influenced by FAT, but not VFAT (e.g., for Si, 9.8 +/- 0.8 in low FAT vs. 4.6 +/- 0.7 x 10(-4)/min/[microIU/mL[ in high FAT, p < 0.05; 6.8 +/- 0.7 in low VFAT vs. 7.5 +/- 0.8 x 10(-4)/min/[microIU/mL] in high VFAT, p > 0.1). In African Americans, fasting insulin and Si were also primarily influenced by FAT (e.g., for Si, 4.9 +/- 0.4 in low FAT vs. 2.8 +/- 0.5 x 10(-4)/min/[microIU/mL] in high FAT, p < 0.05) but not by VFAT, and there were no significant effects of either fat compartment on AIR. In multiple regression analysis, Si was significantly influenced by FAT (negative effect), ethnicity (lower in African Americans), and gender (lower in females), whereas fasting insulin was significantly influenced by VFAT (positive effect), ethnicity (higher in African Americans), and fat free mass (positive effect). DISCUSSION: Body fat in general is the predominant factor influencing Si, but VFAT may have additional effects on fasting insulin. The lack of major effects of VFAT on Si in children may be explained by lower levels of VFAT or because VFAT affects aspects of whole body insulin action that are not measured by the minimal model.

Adipose Tissue↗

Body fat, fat distribution and serum lipids, lipoproteins and apolipoproteins in African-American and Caucasian-American prepubertal children.

OBJECTIVE: The purpose of the present study was to determine the impact of body fat mass and fat distribution on serum lipids, lipoproteins and apolipoproteins in African-American and Caucasian-American prepubertal children. SUBJECTS: Study participants included 62 African-American children (age 8.3+/-1.4 y; body mass 37.3+/-13.6 kg; height 133+/-11 cm) and 39 Caucasian children (age 8.6+/-1.2 y; body mass 34.1+/-11.0 kg; height 131+/-9 cm). METHODS: Venous blood samples were obtained after a 12 h overnight fast and serum was analyzed for total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), triacylglycerol (TAG), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and lipoprotein (a) (Lp(a)) concentrations. Body composition and body fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography, respectively. RESULTS: African-American children had lower TAG (46+/-20 vs 61+/-32 mg/dl, P=0.015) and higher Lp(a) (34+/-25 vs 17+/-28 mg/dl, P=0.001) and HDL-C (44+/-11 vs 39+/-8 mg/dl, P=0.041). There were no ethnic differences in TC, ApoA-I and ApoB (P=0.535, P=0.218, P=0.418, respectively). The ethnic difference in TAG and Lp(a) was not explained by total fat or abdominal fat. The ethnic difference in HDL-C was explained by visceral fat and TAG. CONCLUSION: In prepubertal children, neither body fat nor fat distribution explain the ethnic difference in TAG or Lp(a), but visceral fat and TAG may contribute to differences in HDL-C.

Absorptiometry, Photon↗

A longitudinal study of resting energy expenditure relative to body composition during puberty in African American and white children.

BACKGROUND: Body composition and resting energy expenditure (REE) have not been examined longitudinally during puberty. OBJECTIVE: The purpose of this longitudinal study was to examine the influence of pubertal maturation on REE relative to body composition in African American and white children. DESIGN: The study included 92 white and 64 African American children (mean age at baseline: 8.3 and 7.9 y, respectively) from Birmingham, AL. The children had 2-5 annual measurements of fat mass (FM), lean mass (LM), and REE. The Tanner stages of the children ranged from 1 to 5. Mixed-model repeated-measures analyses were used to test the change in REE relative to body composition with increasing Tanner stage among ethnic and sex groups. RESULTS: LM increased from Tanner stage 1 to subsequent stages. FM relative to LM decreased from Tanner stage 1 to stages 3, 4, and 5 but not from stage 1 to stage 2. The African American children had relatively higher limb LM and lower trunk LM than did the white children. REE declined with Tanner stage after adjustment for ethnicity, sex, FM, and LM. This decline was significant from Tanner stage 1 to stages 3, 4, and 5 but not to Tanner stage 2. After adjustment for age, Tanner stage, FM, and LM or LM distribution, REE was significantly higher in white than in African American children (by approximately 250 kJ/d). CONCLUSION: In a large sample of children at various Tanner stages, we found an ethnic difference in REE after adjustment for age, Tanner stage, FM, and LM that was not explained by the difference in LM distribution.

Basal Metabolism↗

Age-related decrease in resting energy expenditure in sedentary white women: effects of regional differences in lean and fat mass.

BACKGROUND: Lean mass and resting energy expenditure (REE) decrease with age. However, it is unknown whether age-related changes in regional lean and fat mass are responsible for the age-related decrease in REE. OBJECTIVE: Our objective was to determine how regional lean and fat mass vary with age and whether age is independently related to REE after adjustment for regional fat and lean mass. DESIGN: The study was a cross-sectional evaluation of 58 white women aged 23-77 y. Regional and whole-body lean and fat mass were measured by dual-energy X-ray absorptiometry, subcutaneous abdominal tissue (SAT) and intraabdominal adipose tissue (IAF) by computed tomography, and REE by ventilated-canopy indirect calorimetry. RESULTS: Independent of other significant correlates, age was significantly and independently associated with greater IAF (beta = 0.49) and less leg lean mass (beta = -0.35). IAF (r = -0.28) and IAF:SAT (r = -0.31) correlated negatively with REE. REE was negatively associated with greater age (beta = -0.42), independent of changes in lean and fat mass in different parts of the body. By contrast, trunk lean (beta = 0.27) and leg fat (beta = 0.27) mass were associated with greater REE independent of age and other body-composition variables. CONCLUSIONS: These results suggest that trunk lean mass (presumably primarily organ tissue) is relatively resistant to age-related changes in body composition, whereas muscle mass, especially leg muscle, tends to be lost. These data also suggest that the age-related decreases in REE are not fully explained by changes in body composition.

Absorptiometry, Photon↗

Body fat distribution in white and black women: different patterns of intraabdominal and subcutaneous abdominal adipose tissue utilization with weight loss.

BACKGROUND: Intraabdominal adipose tissue (IAAT) is the body fat depot most strongly related to disease risk. Weight reduction is advocated for overweight people to reduce total body fat and IAAT, although little is known about the effect of weight loss on abdominal fat distribution in different races. OBJECTIVE: We compared the effects of diet-induced weight loss on changes in abdominal fat distribution in white and black women. DESIGN: We studied 23 white and 23 black women, similar in age and body composition, in the overweight state [mean body mass index (BMI; in kg/m(2)): 28.8] and the normal-weight state (mean BMI: 24.0) and 38 never-overweight control women (mean BMI: 23.4). We measured total body fat by using a 4-compartment model, trunk fat by using dual-energy X-ray absorptiometry, and cross-sectional areas of IAAT (at the fourth and fifth lumbar vertebrae) and subcutaneous abdominal adipose tissue (SAAT) by using computed tomography. RESULTS: Weight loss was similar in white and black women (13.1 and 12.6 kg, respectively), as were losses of total fat, trunk fat, and waist circumference. However, white women lost more IAAT (P < 0.001) and less SAAT (P < 0.03) than did black women. Fat patterns regressed toward those of their respective control groups. Changes in waist circumference correlated with changes in IAAT in white women (r = 0.54, P < 0.05) but not in black women (r = 0.19, NS). CONCLUSIONS: Despite comparable decreases in total and trunk fat, white women lost more IAAT and less SAAT than did black women. Waist circumference was not a suitable surrogate marker for tracking changes in the visceral fat compartment in black women.

Abdomen↗

Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans.

The mechanism(s) of load-induced muscle hypertrophy is as yet unclear, but increasing evidence suggests a role for locally expressed insulin-like growth factor I (IGF-I). We investigated the effects of concentric (CON) vs. eccentric (ECC) loading on muscle IGF-I mRNA concentration. We hypothesized a greater IGF-I response after ECC compared with CON. Ten healthy subjects (24.4 +/- 0.7 yr, 174.5 +/- 2.6 cm, 70.9 +/- 4.3 kg) completed eight sets of eight CON or ECC squats separated by 6-10 days. IGF-I, IGF binding protein-4 (IGFBP-4), and androgen receptor (AR) mRNA concentrations were determined in vastus lateralis muscle by RT-PCR before and 48 h after ECC and CON. Serum total testosterone (TT) and IGF-I were measured serially across 48 h, and serum creatine kinase activity (CK), isometric maximum voluntary contraction (MVC), and soreness were determined at 48 h. IGF-I mRNA concentration increased 62% and IGFBP-4 mRNA concentration decreased 57% after ECC (P < 0.05). Changes after CON were similar but not significant (P = 0.06-0.12). AR mRNA concentration increased (P < 0.05) after ECC (63%) and CON (102%). Serum TT and IGF-I showed little change. MVC fell 10% and CK rose 183% after ECC (P < 0.05). Perceived soreness was higher (P < 0.01) after ECC compared with CON. Results indicate that a single bout of mechanical loading in humans alters activity of the muscle IGF-I system, and the enhanced response to ECC suggests that IGF-I may somehow modulate tissue regeneration after mechanical damage.

Adult↗

Longitudinal study on pubertal insulin resistance.

Previous cross-sectional studies show that puberty is associated with a reduction in insulin sensitivity (S(I)), but no longitudinal studies have examined this change in detail. This study is a longitudinal study in 60 children (33 male and 27 female subjects; 32 Caucasian and 28 African-American) examined at Tanner stage I (age 9.2 +/- 1.4 years) and after 2.0 +/- 0.6 years of follow-up, by which time 29 children remained at Tanner stage I and 31 had progressed to Tanner stage III or IV. Tanner stage was assessed by physical examination. S(I), the acute insulin response (AIR), and the disposition index (DI) were determined by the tolbutamide-modified intravenous glucose tolerance test and minimal modeling, body fat mass was assessed by dual-energy X-ray absorptiometry, visceral fat was determined by computed tomography, and fasting blood was analyzed for hormone levels. In children progressing to Tanner stage III, S(I) fell significantly by 32% (4.4 +/- 3.0 to 3.0 +/- 1.7 x 10(-4)min(-1)/[microIU/ml]), AIR increased by 30%, DI fell by 27%, and there was a significant increase in fasting glucose (93.5 +/- 5.0 to 97.0 +/- 4.1 mg/dl) and insulin (14.3 +/- 8.1 to 18.6 +/- 11.0 microIU/ml). In children remaining at Tanner stage I, there was a slight increase in S(I) (6.4 +/- 3.1 to 7.4 +/- 3.5 x 10(-4)min(-1)/[microIU/ml]) with no significant change in AIR or fasting glucose and insulin. The pubertal fall in S(I) was more consistent in African-Americans; remained significant after controlling for age, sex, and change in fat mass, visceral fat, and fat-free mass; and was similar in children at low, medium, and high body fat. Change in S(I) was not significantly related to change in fasting hormone levels, but change in AIR was significantly related to change in androstendione (r = 0.39; P = 0.04). Pubertal transition from Tanner stage I to Tanner stage III was associated with a 32% reduction in S(I,) and increases in fasting glucose, insulin, and AIR. These changes were similar across sex, ethnicity, and obesity. The significant fall in DI suggests conservation in beta-cell function or an inadequate beta-cell response to the fall in S(I). The fall in S(I) was not associated with changes in body fat, visceral fat, IGF-I, androgens, or estradiol.

Adipose Tissue↗

Levels of progesterone, testosterone, and estradiol, and androstenedione metabolism in the gonads of Lytechinus variegatus (Echinodermata:echinoidea).

Levels of progesterone (P4), testosterone (T) and estradiol (E2) indicated significant variation among individual echinoids during the annual cycle, reflecting generally the variation in gamete development that can be observed among individuals. Testosterone and E2 levels in both the ovaries and testes were higher during the period of gonadal growth. Levels of all steroids were greatly reduced compared to those levels reported for asteroids. Differences in the levels of P4, T, and estrogens between asteroids and Lytechinus variegatus may be related to differences in gonad morphology and nutrient storage capacity between asteroids and echinoids. It was hypothesized that the low levels of steroids detected in L. variegatus reflect paracrine-like mechanisms in cell signaling as compared to endocrine-like mechanisms proposed to be involved in regulating gonad function in asteroids. Both the ovaries and testes of L. variegatus had the capacity to synthesize T and a variety of 5alpha-reduced androgens including 5alpha-androstane-3beta,17beta-diol and 5alpha-androstane-3alpha,17beta-diol (5alpha-adiols) from androstenedione (AD) in 8 h. Estrogen synthesis was not detected. The sex-specific pattern of accumulation of 5alpha-adiols in the ovaries and testes suggests that the 5alpha-adiols may affect processes related to reproduction in L. variegatus.

Androstenedione↗

Racial differences in insulin secretion and sensitivity in prepubertal children: role of physical fitness and physical activity.

OBJECTIVE: To investigate in prepubertal children whether physical fitness and/or physical activity are: 1) associated with insulin secretion and sensitivity and 2) account for racial differences in insulin secretion and sensitivity. RESEARCH METHODS AND PROCEDURES: Subjects included 34 African American and 34 white nondiabetic children aged 5 to 11 years. Data were divided into two sets according to the availability of VO2max and physical activity data. Body composition was measured by dual-energy X-ray absorptiometry. Subcutaneous abdominal adipose tissue and intra-abdominal adipose tissue were examined by computed tomography. Insulin sensitivity (S1) and acute insulin response (AIR) were determined by a frequently sampled intravenous glucose tolerance test. An all-out, progressive treadmill exercise test was used for measuring VO2max. Physical activity data were collected by questionnaire. RESULTS: African American children had lower SI and higher AIR than white children, after adjusting for total body fat mass. African Americans reported higher levels of physical activity (hours/wk) than whites, but had a lower VO2max. In multiple linear regression analysis, hours/wk of activity and hours/wk of vigorous activity, but not moderate activity, were independently related to SI and AIR after adjusting for race, total body fat mass or fat distribution, and total lean tissue mass. VO2max was not related to AIR, and was inversely related to SI, after adjusting for body composition. Race remained significantly associated with both SI and AIR, even after adjusting for body composition, fat distribution, and hours/wk of activity or hours/wk of vigorous activity. DISCUSSION: In summary, overall physical activity and, especially, vigorous activity were associated with insulin secretion and sensitivity. However, neither physical activity nor VO2max explained the racial difference in insulin secretion (higher in African Americans) and sensitivity (lower in African Americans). Thus, racial (African American to white) differences in aspects of insulin action seem to be due to factors other than body composition, fat distribution, cardiovascular fitness, and amount of physical activity.

Absorptiometry, Photon↗

Role of dietary factors in ethnic differences in early risk of cardiovascular disease and type 2 diabetes.

BACKGROUND: The disparity in the prevalence of cardiovascular disease and type 2 diabetes between African Americans and whites has been well established, and ethnic differences in several risk factors for these diseases are evident in childhood. OBJECTIVE: The current study explored whether dietary factors explain ethnic differences in serum lipids and insulin profiles in children, independent of body composition and social class background. DESIGN: The sample included 95 African American and white children (mean age: 10.0 y). Macronutrient and food group intakes were derived from three 24-h recalls. Cardiovascular disease and type 2 diabetes risk were determined on the basis of total cholesterol, triacylglycerol, insulin sensitivity (S(i)), and acute insulin response (AIR). Data were analyzed by using t tests, analysis of covariance, and multiple regression. RESULTS: African American children had lower triacylglycerol (P < 0.01), lower S(i) (P < 0.001), and higher AIR (P < 0.001) than whites. Intake of fruit and vegetables was significantly higher, and dairy intake lower, in African American than in white children after adjustment for social class and total energy intake. Several direct relations were observed between diet and insulin action: carbohydrate and fruit intakes were positively associated with S(i) (P = 0.02), and vegetable intake was negatively associated with AIR (P = 0.01). However, neither macronutrient nor food group intake accounted for the ethnic differences in triacylglycerol and AIR. CONCLUSIONS: The African American children in our sample showed a greater disease risk than did the white children, even after body composition, social class background, and dietary patterns were adjusted for.

Adolescent↗

Associations among oral estrogen use, free testosterone concentration, and lean body mass among postmenopausal women.

Circulating concentrations of sex hormone-binding globulin (SHBG) are increased by use of oral estrogen. The objective of this study was to determine whether postmenopausal women who used oral estrogen had higher serum concentrations of SHBG and lower serum concentrations of free testosterone (T) than nonusers, and whether free T was associated with lean body mass, particularly skeletal muscle mass. Subjects were 70 postmenopausal women, 46-55 yr old, 46 of whom used oral estrogen. Total and regional body composition were determined by dual-energy x-ray absorptiometry. Serum concentrations of SHBG, total T, and estradiol (E(2)) were determined by RIA. Free T was calculated from concentrations of total T and SHBG. Hormone users had higher serum concentrations of E(2) and SHBG (182.0 +/- 58. 5 vs. 82.9 +/- 41.1 nmol/L, mean +/- SD, P: < 0.001) and lower concentrations of free T (3.7 +/- 2.2 vs. 7.9 +/- 4.1 pmol/L, mean +/- SD, P: < 0.001); total T did not differ. Total lean mass and leg lean mass were significantly correlated with free, but not total T [r values of 0.29 (P: < 0.05) and 0.31 (P: < 0.01) for total and leg lean mass, respectively, vs. free T]; arm lean mass was not correlated with either measure of T. Serum E(2) was significantly correlated with SHBG (r = 0.50, P: < 0.001) and free T (r = -0.33, P: < 0.01). These observations imply that, by reducing the concentration of bioavailable T, oral estrogen therapy may accelerate or augment lean mass loss among postmenopausal women. This conclusion awaits confirmation by longitudinal observation.

Body Composition↗

Leptin in postmenopausal women: influence of hormone therapy, insulin, and fat distribution.

Whether use of hormone-replacement therapy (HRT) influences menopause-related changes in body weight is unclear. HRT may affect energy balance by influencing synthesis of the adipocyte-derived hormone leptin. The objectives of this study were to: 1) identify factors influencing circulating leptin in postmenopausal women; 2) determine whether HRT influences serum leptin after adjusting for confounding factors; and, 3) identify potential independent effects of HRT or leptin on resting energy expenditure (REE). Subjects were 54 postmenopausal women, 45-55 yr old, 35 of whom used HRT (estrogen plus progestin). Total and regional body composition and fat distribution were determined by dual-energy x-ray absorptiometry and computed tomography; fasting serum leptin and insulin, by RIA; and REE, by indirect calorimetry. Stepwise multiple linear regression analysis indicated that serum leptin could best be predicted from total fat mass, fasting serum insulin, and total lean mass [log leptin = 1.08 x log fat mass) + (0.46 x log insulin) + (-1.25 x log lean mass) + 1.88; model R2 = 0.78, P < 0.001]. Multiple linear regression analysis indicated that visceral fat was independently related to leptin (parameter estimate = 0.23, P < 0.05), after adjusting for s.c. abdominal fat and leg fat, as well as lean mass and insulin. After adjusting for total fat mass, total lean mass, and fasting insulin, serum leptin did not differ between users and nonusers of HRT (21.7 +/- 1.0 vs. 20.2 +/- 1.3 ng/mL, P = 0.369, adjusted mean +/- SE, respectively). Serum estradiol was inversely correlated with (adjusted) leptin in non-HRT users (r = -0.50), suggesting that ovarian senescence may lead to an increase in leptin. Multiple linear regression analysis indicated that REE (adjusted for fat mass, fat-free mass, and ethnicity) was not associated with leptin (P = 0.298) or hormone use status (P = 0.999; 1323 +/- 31 vs. 1316 +/- 42 kcal/day, adjusted mean +/- SE for users and nonusers, respectively). These results indicate that, in postmenopausal women: 1) total fat mass, lean mass, and fasting insulin, but not HRT, are significant determinants of serum leptin; 2) visceral and s.c. fat contribute to serum leptin; and, 3) neither HRT nor leptin is independently related to REE.

Absorptiometry, Photon↗

Transgenic studies of fatty acid oxidation gene expression in nonobese diabetic mice.

Type 1 diabetes mellitus is a devastating disorder affecting both glucose and lipid metabolism. Using the nonobese diabetic (NOD) mouse model, we found that diabetic mice had a liver-specific increase in steady state mRNA levels for enzymes involved in oxidation of fatty acids. Increased mRNA abundance was observed in very long-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase (LCAD), medium-chain acyl-CoA dehydrogenase (MCAD), carnitine palmitoyltransferase I (CPT-1a), and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, whereas short-chain acyl-CoA dehydrogenase mRNA remained unchanged. In contrast, minimal elevations in LCAD and CPT-1a mRNA were observed in hearts of diabetic mice with no significant differences found for the other enzymes. We developed NOD mice with transgenes containing regulatory elements of human MCAD gene controlling a reporter gene to determine if the increase in MCAD gene expression occurred via the well-characterized nuclear receptor response element (NRRE-1). These results demonstrated that the transgene containing the NRRE-1 and adjacent 5' sequences had elevated liver expression in diabetic mice compared with prediabetic or normal control mice. Surprisingly, the transgene that contains NRRE-1 with adjacent 3' sequences and the transgene with the NRRE-1 deleted showed minimal response to the fulminant diabetic condition.Collectively, these results indicate that in type 1 diabetes there exists an excessive and liver-specific activation of fatty acid oxidation gene expression. Using human MCAD as a prototype gene, we have shown that this increased expression is mediated at the transcriptional level but does not occur via the well-characterized NRRE-1 site responsible for baseline expression in normal mice.

Acyl-CoA Dehydrogenase, Long-Chain↗

Predicting body composition from anthropometry in pre-adolescent children.

The objectives of this paper were to: a) evaluate the accuracy and precision of previously published pediatric body composition prediction equations and b) develop additional prediction equations from a large, heterogeneous group of Caucasian (n = 133) and African-American (n = 69) children. The combined cohort of 202 children included a wide range of ages (4.0-10.9 y), weights (14.0-70.8 kg), fat mass (FM: 1.2-28.5 kg) and percent body fat (% body fat: 6.2-49.6%). Skinfold measurements were obtained using a Lange caliper and body fat was measured with a Lunar DPX-L densitometer. The previously published equations of Slaughter et al and Goran et al did not accurately predict body fat. The entire cohort was randomly divided into two sub-groups for purposes of deriving and cross-validating a new prediction equation. In stepwise regression analysis in the development group (n = 135), weight, triceps skinfold, gender, ethnicity and abdominal skinfold estimated FM measured by dual energy x-ray absorptiometry (DEXA) with a model R2 of 0.95. The new prediction equation was cross-validated in the control group (n = 67) and each ethnic and gender subgroup. We conclude that a) the equations of Slaughter et al and Goran et al did not accurately predict FM in a heterogeneous group of children and b) a new anthropometric prediction equation is proposed that may provide accurate estimates of FM in both Caucasian and African-American children aged 4-10 y with a wide range of FM and body composition.

Alabama↗