The Association between Plasma Adiponectin and Insulin Sensitivity in Humans Depends on Obesity

Objective: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. Research Methods and Procedures: We investigated the cross‐sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose‐tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. Results: In cross‐sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin × PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R² = 0.10, p = 0.13, OGTT; and R² = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R² = 0.36, p < 0.0001, OGTT; and R² = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. Discussion: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin‐resistant individuals.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.     

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

Objective: To examine the relationship between fasting plasma leptin and 24‐hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. Research Methods and Procedures: Twenty‐one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m²) and 13 lean (body mass index: 20.4 to 24.7 kg/m²) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1–23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty‐four‐hour EE and substrate oxidations were measured by whole‐body indirect calorimetry. SPA was assessed by microwave radar. Results: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24‐hour EE before (r = ?0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24‐hour and resting nonprotein respiratory quotient (r = ?0.47, p < 0.05 and r = ?0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = ?0.41, p = 0.07), 16 weeks (r = ?0.51, p < 0.05), and 24 weeks (r = ?0.50, p < 0.05). Discussion: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.     

The effect of moderate alcohol consumption on fat distribution and adipocytokines

Objective: To investigate the effect of moderate alcohol consumption on fat distribution, adipose tissue secreted proteins (adiponectin and resistin), and insulin sensitivity in healthy middle‐aged men with abdominal obesity. Research Methods and Procedures: Thirty‐four healthy men between 35 and 70 years old, with increased waist circumference (≥94 cm), participated in a randomized, controlled cross‐over design trial. They drank 450 mL of red wine (40 grams of alcohol) or 450 mL of de‐alcoholized red wine daily during 4 weeks. At the end of each treatment period, fat distribution, adipose tissue proteins, and insulin sensitivity index (ISI) were measured. Results: Subcutaneous and abdominal fat contents and body weight did not change after 4 weeks of moderate alcohol consumption. Liver fat (quip index) was slightly higher after consumption of red wine (6.8 ± 0.1) as compared with de‐alcoholized red wine (6.5 ± 0.1) but not significantly different (p = 0.09). Plasma adiponectin concentration increased (p < 0.01) to 6.0 ± 0.1 μg/mL after 28 days of moderate alcohol consumption compared with de‐alcoholized red wine (5.5 ± 0.1 μg/mL). Serum resistin concentrations and ISI were not affected by alcohol consumption. Percentage changes in serum resistin correlated significantly with changes in ISI (r = ?0.69, p < 0.01), whereas this correlation was not present between changes in plasma adiponectin and ISI (r = 0.31, p = 0.22). Discussion: Moderate alcohol consumption for 4 weeks is not associated with differences in subcutaneous and abdominal fat contents or body weight. Thus, the 10% increase in adiponectin was not associated with a change in fat distribution or body weight change.     

Validation and Calibration of Physical Activity Monitors in Children

Objective: This study was designed to validate accelerometer-based activity monitors against energy expenditure (EE) in children; to compare monitor placement sites; to field-test the monitors; and to establish sedentary, light, moderate, and vigorous threshold counts. Research Methods and Procedures: Computer Science and Applications Actigraph (CSA) and Mini-Mitter Actiwatch (MM) monitors, on the hip or lower leg, were validated and calibrated against 6-hour EE measurements by room respiration calorimetry, activity by microwave detector, and heart rate by telemetry in 26 children, 6 to 16 years old. During the 6 hours, the children performed structured activities, including resting metabolic rate (RMR), Nintendo, arts and crafts, aerobic warm-up, Tae Bo, treadmill walking and running, and games. Activity energy expenditure (AEE) computed as EE − RMR was regressed against counts to derive threshold counts. Results: The mean correlations between EE or AEE and counts were slightly higher for MM-hip (r = 0.78 ± 0.06) and MM-leg (r = 0.80 ± 0.05) than CSA-hip (r = 0.66 ± 0.08) and CSA-leg (r = 0.73 ± 0.07). CSA and MM performed similarly on the hip (inter-instrument r = 0.88) and on the lower leg (inter-instrument r = 0.89). Threshold counts for the CSA-hip were <800, <3200, <8200, and ≥8200 for sedentary, light, moderate, and vigorous categories, respectively. For the MM-hip, the threshold counts were <100, <900, <2200, and ≥2200, respectively. Discussion: The validation of the CSA and MM monitors against AEE and their calibration for sedentary, light, moderate, and vigorous thresholds certify these monitors as valid, useful devices for the assessment of physical activity in children.     

Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans

Objective: To explore the potential role of the endogenous peptide YY (PYY) in the long‐term regulation of body weight and energy homeostasis. Research Methods and Procedures: Fasting and postprandial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21 men/8 women) non‐diabetic subjects, 16 of whom had a follow‐up visit 10.8 ± 1.4 months later. Ratings of hunger and satiety were collected using visual analog scales. Resting metabolic rate (RMR) (15‐hour RMR) and respiratory quotient (RQ) were assessed using a respiratory chamber. Results: Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15‐hour RMR (r = ?0.46, p = 0.01). Postprandial changes in PYY (area under the curve) were positively associated with postprandial changes in ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved after the meal (peak PYY) were negatively associated with 24‐hour RQ (r = ?0.41, p = 0.03). Prospectively, the peak PYY concentrations were negatively associated with changes in body weight (r = ?0.58, p = 0.01). Discussion: Our data indicate that the endogenous PYY may be involved in the long‐term regulation of body weight. It seems that this long‐term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism.     

Effect of a thermogenic beverage on 24-hour energy metabolism in humans

Objective: To test whether consumption of a beverage containing active ingredients will increase 24‐hour energy metabolism in healthy, young, lean individuals. Research Method and Procedures: Thirty‐one male and female subjects consumed 3 × 250‐mL servings of a beverage containing green tea catechins, caffeine, and calcium for 3 days in a single‐center, double‐blind, placebo‐controlled, cross‐over design study. On the 3rd day, 23‐hour energy metabolism, extrapolated to 24‐hour, was measured in a calorimeter chamber. Blood pressure and heart rate were measured, and total day and night urines were analyzed for urea and catecholamine excretion. Results: Twenty‐four‐hour energy expenditure (EE) and 24‐hour fat oxidation were lower in women than in men (p < 0.0001 and p < 0.015, respectively). Although there were no treatment or treatment/gender effects on substrate oxidation, treatment increased 24‐hour EE by 106 ± 31 kcal/24 hours (p = 0.002), equivalent to 4.7 ± 1.6 kcal/h (day; p = 0.005) and 3.3 ± 1.5 kcal/h (night; p = 0.04). No significant differences were observed in hemodynamic parameters. Discussion: The present study provides evidence that consumption of a beverage containing green tea catechins, caffeine, and calcium increases 24‐hour EE by 4.6%, but the contribution of the individual ingredients cannot be distinguished. Although this increase is modest, the results are discussed in relation to proposed public health goals, indicating that such modifications are sufficient to prevent weight gain. When consumed regularly as part of a healthy diet and exercise regime, such a beverage may provide benefits for weight control.     

Ghrelin and the Hyposomatotropism of Obesity

Objective: Human obesity is characterized by growth hormone (GH) deficiency, which appears primarily related to a central pattern of obesity and is reverted on weight loss. As yet, the metabolic basis of the GH deficiency remains to be elucidated. The recently discovered endogenous ligand for the GH secretagogue receptor, ghrelin, stimulates GH secretion when administered to rodents or healthy humans. It may thus be hypothesized that low ghrelin levels underlie the hyposomatropism in obesity. Research Methods and Procedures: We have tested this hypothesis in individuals with widely varying body mass and fat distribution and evaluated whether the improved GH concentrations on weight loss are associated with enhanced ghrelin levels. Results: Both plasma GH and ghrelin levels were reciprocally related with body mass index (r = −0.67, p < 0.001). However, whereas 24-hour GH secretion was negatively related to the visceral fat area (r = −0.72, p < 0.01), ghrelin levels showed a positive relationship with the visceral fat area (r = 0.49, p < 0.02). Weight loss resulted in increased GH secretion (median 24-hour GH area under the curve: 1983 vs. 4024 mU/day before and after weight loss, respectively; p < 0.01) but did not affect ghrelin levels. No relationship could be found between GH and ghrelin plasma levels in obese subjects when comparing diurnal concentration profiles. Discussion: We showed that plasma ghrelin and GH levels are both reciprocally related with body mass index, but no causative relationship could be demonstrated between low ghrelin levels and the hyposomatropism in human obesity.     

In Utero Gender Dimorphism of Adiponectin Reflects Insulin Sensitivity and Adiposity of the Fetus

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin‐sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. To further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition, and gender. Umbilical cord adiponectin, adiponectin complexes, and metabolic parameters were measured at term by elective cesarean delivery. The associations between adiponectin, measures of body composition, and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in female compared with male fetuses (34.3 ± 9.5 vs. 24.9 ± 8.6, P < 0.001) were associated with a 3.2‐fold greater abundance in circulating HMW complexes (0.20 ± 0.03 vs. 0.08 ± 0.03, P < 0.001, n = 9). Adiponectin was positively correlated with neonatal fat mass (r = 0.27, P < 0.04) and percent body fat in female fetuses (r = 0.28, P < 0.03) and with lean mass in males (r = 0.28, P < 0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.     

Plasma Leptin Response to an Epinephrine Infusion in Lean and Obese Women

Objective: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. Research Methods and Procedures: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 μg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index ± SD: 22.6 ± 1.1 kg/m²) and 15 obese (30.0 ± 1.3 kg/m²) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (−15 and 0 minutes) and at every 30 minutes over the 90-minute period. Results: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = −0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from −12 to −570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = −0.14, p = 0.55). Discussion: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.     

Twenty-four-hour metabolic responses to resistance exercise in women

Seven nonobese adult females (40 +/- 8 years) were studied in a room calorimeter on a day that resistance exercise (REX) was performed (4 sets of 10 exercises) and on a nonexercise control day (CON). Twenty-four-hour energy expenditure (EE) on the REX day (mean +/- SD, 2,328 +/- 327 kcal.d(-1)) was greater than CON (2,001 +/- 369 kcal.d(-1), p < 0.001). The net increase in EE during and immediately after (30 minutes) exercise represented 76 +/- 12% of the total increase in 24-hour EE. Twenty four-hour RQ on the REX day (0.86 +/- 0.06) did not differ from CON (0.87 +/- 0.02). Twenty four-hour carbohydrate oxidation was elevated on the REX day, but 24-hour fat and protein oxidation were not different. Thus, in women, the increase in EE due to resistance exercise is largely seen during and immediately after the exercise. The increased energy demand is met by increased carbohydrate oxidation, with no increase in 24-hour fat oxidation.     

Higher 24‐h Respiratory Quotient and Higher Spontaneous Physical Activity in Nighttime Eaters

We have previously shown that a higher 24‐h respiratory quotient (24‐h RQ) predicts greater ad‐libitum food intake and that nighttime eaters (NE) ingested more calories during an in‐patient food intake study and gained more weight over time. We investigated whether 24‐h RQ was higher in individuals who exhibited nighttime eating behavior. Healthy nondiabetic Pima Indians (PI; n = 97, 54 male/43 female) and whites (W; n = 32, 22 male/10 female) were admitted to our Clinical Research Unit. After 3 days of a weight maintaining diet, 24‐h energy expenditure (24‐h EE), 24‐h RQ, rates of carbohydrate (CHOX) and lipid oxidation (LIPOX), and spontaneous physical activity (SPA) were measured in a metabolic chamber whereas volunteers were in energy balance and unable to consume excess calories. Individuals subsequently ate ad libitum from a computerized vending machine for 3 days with amount and timing of food intake recorded. Fifty‐five individuals (36%; 39 PI, 16 W) were NE, who ate between 11 pm and 5 am on at least one of the 3 days on the vending machines. There were no differences in BMI or percentage body fat between NE and non‐NE. After adjusting for age, sex, race, fat‐free mass, fat mass, and energy balance, NE had a higher 24‐h RQ (P = 0.01), higher CHOX (P = 0.009), and lower LIPOX (P = 0.03) and higher 24‐h SPA (P = 0.04) compared to non‐NE. There were no differences in adjusted 24‐h EE or sleep RQ between the groups. Individuals with nighttime eating behavior have higher 24‐h RQ, higher CHOX and lower LIPOX, a phenotype associated with increased food intake and weight gain.     

Effects of pronounced weight loss on adiponectin oligomer composition and metabolic parameters

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters. Research Methods and Procedures: Thirteen severely obese female subjects were examined before and 1 year after surgical treatment. Total adiponectin was determined by radioimmunosorbent assay, and oligomer composition was detected by nondenaturing Western blot. Results: BMI decreased substantially (p < 0.001), which was associated with an increase of total adiponectin from 12.9 ± 5.9 to 14.3 ± 6.1 μg/mL (p = 0.055). Medium molecular weight (MMW) adiponectin increased from 7.5 ± 3.6 to 9.1 ± 4.1 μg/mL (p = 0.009), whereas high (HMW) and low molecular weight adiponectin remained unchanged. Δ values of total adiponectin correlated significantly with Δ values of anthropometric parameters. Similar correlations were found for Δ values of MMW (Δ weight: r² = 0.4132, p = 0.0178; Δ BMI: r² = 0.3319, p = 0.0393; Δ fat mass: r² = 0.5202, p = 0.0054). Discussion: Thus, profound weight loss was associated with an increase in total adiponectin, which was mainly and consistently caused by increases in MMW adiponectin (p = 0.009). These changes result in a shift from low molecular weight to MMW and HMW adiponectin isoforms, which may be related to improvements in both anthropometric and metabolic parameters.     

Relationship of Serum Adiponectin and Leptin Concentrations with Body Fat Distribution in Humans

Objective: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin. Research Methods and Procedures: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist‐to‐hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of the lower leg as assessed by magnetic resonance imaging. Results: After adjusting for sex and percentage of body fat, adiponectin was negatively (r = ?0.17, p < 0.001) and leptin was positively (r = 0.22, p < 0.001) correlated with waist‐to‐hip ratio. Leptin, but not adiponectin, correlated with both waist (r = 0.49, p < 0.001) and hip circumference (r = 0.46, p < 0.001). Furthermore, leptin, but not adiponectin, correlated with the proportion of subcutaneous fat of the lower leg cross‐sectional area (r = 0.37, p < 0.001). Discussion: These data suggest that both adipocytokines are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment.     

Impact of Visceral Fat on Blood Pressure and Insulin Sensitivity in Hypertensive Obese Women

Objective: The relationship among body fat distribution, blood pressure, serum leptin levels, and insulin resistance was investigated in hypertensive obese women with central distribution of fat. Research Methods and Procedures: We studied 74 hypertensive women (age, 49.8 ± 7.5 years; body mass index, 39.1 ± 5.5 kg/m²; waist-to-hip ratio, 0.96 ± 0.08). All patients were submitted to 24-hour blood pressure ambulatory monitoring (24h-ABPM). Abdominal ultrasonography was used to estimate the amount of visceral fat (VF). Fasting blood samples were obtained for serum leptin and insulin determinations. Insulin resistance was estimated by homeostasis model assessment insulin resistance index (HOMA-r index). Results: Sixty-four percent of the women were postmenopausal, and all patients showed central distribution of fat (waist-to-hip ratio > 0.85). The VF correlated with systolic 24h-ABPM values (r = 0.28, p = 0.01) and with HOMA-r index (r = 0.27; p = 0.01). VF measurement (7.5 ± 2.3 vs. 5.9 ± 2.2 cm, p < 0.001) and the systolic 24h-ABPM (133 ± 14.5 vs. 126 ± 9.8 mm Hg, p = 0.04), but not HOMA-r index, were significantly higher in the postmenopausal group (n = 48) than in the premenopausal group (n = 26). No correlations were observed between blood pressure levels and HOMA-r index, leptin, or insulin levels. In the multiple regression analysis, visceral fat, but not age, body fat mass, or HOMA-r index, correlated with the 24h-ABPM (p = 0.003). Discussion: In centrally obese hypertensive women, the accumulation of VF, more often after menopause, is associated with higher levels of blood pressure and insulin resistance. The mechanism through which VF contributes to higher blood pressure levels seems to be independent of leptin or insulin levels.     

Plasma Adiponectin Levels in High Risk African‐Americans with Normal Glucose Tolerance,Impaired Glucose Tolerance,and Type 2 Diabetes**

Objective: We studied plasma adiponectin, insulin sensitivity, and insulin secretion before and after oral glucose challenge in normal glucose tolerant, impaired glucose tolerant, and type 2 diabetic first degree relatives of African‐American patients with type 2 diabetes. Research Methods and Procedures: We studied 19 subjects with normal glucose tolerance (NGT), 8 with impaired glucose tolerance (IGT), and 14 with type 2 diabetes. Serum glucose, insulin, C‐peptide, and plasma adiponectin levels were measured before and 2 hours after oral glucose tolerance test. Homeostasis model assessment‐insulin resistance index (HOMA‐IR) and HOMA‐β cell function were calculated in each subject using HOMA. We empirically defined insulin sensitivity as HOMA‐IR < 2.68 and insulin resistance as HOMA‐IR > 2.68. Results: Subjects with IGT and type 2 diabetes were more insulin resistant (as assessed by HOMA‐IR) when compared with NGT subjects. Mean plasma fasting adiponectin levels were significantly lower in the type 2 diabetes group when compared with NGT and IGT groups. Plasma adiponectin levels were 2‐fold greater (11.09 ± 4.98 vs. 6.42 ± 3.3811 μg/mL) in insulin‐sensitive (HOMA‐IR, 1.74 ± 0.65) than in insulin‐resistant (HOMA‐IR, 5.12 ± 2.14) NGT subjects. Mean plasma adiponectin levels were significantly lower in the glucose tolerant, insulin‐resistant subjects than in the insulin sensitive NGT subjects and were comparable with those of the patients with newly diagnosed type 2 diabetes. We found significant inverse relationships of adiponectin with HOMA‐IR (r = ?0.502, p = 0.046) and with HOMA‐β cell function (r = ?0.498, p = 0.042) but not with the percentage body fat (r = ?0.368, p = 0.063), serum glucose, BMI, age, and glycosylated hemoglobin A1C (%A1C). Discussion: In summary, we found that plasma adiponectin levels were significantly lower in insulin‐resistant, non‐diabetic first degree relatives of African‐American patients with type 2 diabetes and in those with newly diagnosed type 2 diabetes. We conclude that a decreased plasma adiponectin and insulin resistance coexist in a genetically prone subset of first degree African‐American relatives before development of IGT and type 2 diabetes.     

Relationship Between Birth Weight and Body Composition,Energy Metabolism,and Sympathetic Nervous System Activity Later in Life

Objective: Epidemiological studies suggest that high birth weight might be associated with an increased risk of obesity later in life. Programming of metabolic, endocrine, and/or autonomic pathways during intrauterine development has been proposed to explain this association. Research Methods and Procedures: To determine the relationship between birth weight and body composition and energy metabolism later in life, we measured fat mass and fat‐free mass (hydrodensitometry or double‐energy X‐ray absorptiometry), 24‐hour energy expenditure, sleeping metabolic rate, and 24‐hour respiratory quotient (respiratory chamber) in 272 adult nondiabetic Pima Indians (161 males/111 females, age 25 ± 5 years, mean ± SD). In these subjects, birth weight varied over a wide range (2000 to 5000 g). Individuals known to be offspring of diabetic pregnancies were excluded. In 44 of the 272 subjects, muscle sympathetic nerve activity was assessed by microneurography. Results: Birth weight was positively correlated with adult height (r = 0.20, p < 0.001) and fat‐free mass (r = 0.21, p < 0.001), but not with fat mass (r = 0.01, not significant). Sleeping metabolic rate, adjusted for age, sex, fat‐free mass, and fat mass, was negatively related to birth weight (r = ?0.13, p < 0.05), whereas adjusted 24‐hour energy expenditure (r = 0.07, not significant) and 24‐hour respiratory quotient (r = ?0.09, not significant) were not. There was no relationship between birth weight and muscle sympathetic nerve activity (r = 0.12, not significant, n = 44). Discussion: In Pima Indians who are not offspring of diabetic pregnancies, high birth weight is associated with increased height and lean body mass, but not with increased adiposity later in life. Although high birth weight may be associated with relatively low resting energy expenditure, it is not associated with major abnormalities in 24‐hour energy metabolism or with low muscle sympathetic nerve activity later in life.     

Association of Physical Activity and Visceral Adipose Tissue in Older Women and Men

Objective: Physical inactivity, abdominal fat, and age are known risk factors for diabetes, cardiovascular disease, and certain cancers. Previous evidence supports an inverse relationship between physical activity (PA) and abdominal fat estimated by waist circumference. However, few investigations used computed tomography (CAT) scanning for precise measures of abdominal fat. Research Methods and Procedures: Sixty-five female and 106 male (age, 64.5 ± 5.2 years) participants in the Prostate, Lung, Colon and Ovarian Cancer Screening Trial underwent a cross-sectional L4–L5 CAT scan to differentiate visceral adipose tissue (VAT). Subjects were also interviewed by phone to determine PA and physical difficulties (PD). Results: Women had lower VAT (170 ± 84 vs. 205 ± 95 cm², p = 0.014), lower VAT/total fat (29.9 ± 7.2% vs. 42.6 ± 10.2%, p < 0.001), and higher total fat (596 ± 385 vs. 482 ± 183 cm², p = 0.010) than men. PA was inversely correlated to VAT (r = −0.164, p = 0.034) and total fat (r = −0.231, p = 0.003) in men and women. Those who reported a PD had higher VAT (249 vs. 180 cm², p < 0.001) and total fat (652 vs. 500 cm², p = 0.008). Multiple regression analysis indicated total PA and PD were independently associated to VAT and total fat. Discussion: This investigation suggests a beneficial effect of PA and a negative influence of PD on abdominal fat accumulation. Although the cross-sectional design limits cause-effect designations, these results are consistent with other studies showing PA/abdominal fat relation.     

Pleiotropic Effects of Genes for Insulin Resistance on Adiposity in Baboons

Objective: Previous research has suggested a genetic contribution to the development of insulin resistance and obesity. We hypothesized that the same genes influencing insulin resistance might also contribute to the variation in adiposity. Research Methods and Procedures: A total of 601 (200 male, 401 female) adult baboons (Papio hamadryas) from nine families with pedigrees ranging in size from 43 to 121 were used in this study. Plasma insulin, glucose, C‐peptide, and adiponectin were analyzed, and homeostasis model assessment of insulin resistance (HOMA IR) was calculated. Fat biopsies were collected from omental fat tissue, and triglyceride concentration per gram of fat tissue was determined. Body weight and length were measured, and BMI was derived. Univariate and bivariate quantitative genetic analyses were performed using SOLAR. Results: Insulin, glucose, C‐peptide, and adiponectin levels, HOMA IR, triglyceride concentration of fat tissue, body weight, and BMI were all found to be significantly heritable, with heritabilities ranging from 0.15 to 0.80. Positive genetic correlations (r_Gs) were observed for HOMA IR with C‐peptide (r_G = 0.88 ± 0.10, p = 0.01), triglyceride concentration in fat tissue (r_G = 0.86 ± 0.33, p = 0.02), weight (r_G = 0.50 ± 0.20, p = 0.03), and BMI (r_G = 0.64 ± 0.22, p = 0.02). Discussion: These results suggest that a set of genes contributing to insulin resistance also influence general and central adiposity phenotypes. Further genetic research in a larger sample size is needed to identify the common genes that constitute the genetic basis for the development of insulin resistance and obesity.