Interrelationships between body weight, body fat distribution and insulin in obese women before and after hypocaloric feeding and weight loss

The effects were investigated of weight loss on the relationship between hyperinsulinemia, body weight and body fat distribution in two groups of women with central-type obesity (CTO) (waist-to-hip ratio WHR greater than 0.85) or peripheral-type obesity (PTO) (WHR less than 0.85). An oral glucose tolerance test was carried out before and after a hypocaloric nutritional treatment lasting 4 months. Both groups were matched for age, body mass index and amount of body fat. At the basal condition, group CTO had fasting and glucose-stimulated insulin levels significantly higher than group PTO; fasting (but not stimulated) C peptide levels were also higher in CTO compared with PTO. Weight and fat loss were significantly higher in CTO than in PTO women. Moreover, unlike PTO, CTO subjects significantly reduced their WHR values. In both groups weight loss led to a significant drop in fasting and glucose-stimulated insulin and C peptide levels. However, PTO women reduced their C peptide levels significantly less than CTO. In conclusion, weight loss only modified body fat distribution in women with CTO, who appeared to be prone to a greater weight loss than the PTO women. Compared to PTO, CTO women were characterized by higher insulin levels and peripheral insulin resistance, which improved during hypocaloric feeding probably due to the combined effect of weight loss and the change in body fat distribution.     

Comparison of different methods to assess body composition of weight loss in obese and diabetic patients

Recombinant human epidermal growth factor (REGEN-D 150), which was cloned and over expressed in E. coli, has shown enhanced healing of chronic diabetic foot ulcers (DFU) by significantly reducing the duration of healing in addition to providing excellent quality of wound healing and reepithelization. Post-marketing surveillance (PMS) study of REGEN-D 150 in 135 patients of DFU in India was compared with Phase III clinical trial data of REGEN-D 150 in India. Statistical analysis of study data determined that the empirical survival probability distribution, in terms of non-healing of ulcers, was lowest in the case of PMS study, better than that for Phase III; more DFU patients were healed in PMS study. Percentage of patients cured in any given week (e.g., in week 10) is above 90% in PMS study, as compared to 69% in Phase III clinical trial; this percentage was around 18% for the control group with placebo in the Phase III trial. The average wound healing time was significantly lower in PMS study, 4.8 weeks, while it was 9 weeks in Phase III clinical trials while the average wound healing with REGEN-D 150 was found to be 86% in this study. REGEN-D 150 has been found to result in healthy granulation and stimulate epithelization, thus leading to final wound closure. The PMS study has established the efficacy of REGEN-D 150 in faster healing of diabetic foot ulcers.     

Melatonin improves insulin sensitivity independently of weight loss in old obese rats

In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8‐ and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1‐fold increase both after 8‐ and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. The acute insulin‐induced phosphorylation of the analyzed ISP proteins increased 1.3‐ and 2.3‐fold after 8‐ and 12 wk of melatonin supplementation. The total protein content of the insulin receptor (IR) and the IR substrates (IRS‐1, 2) remained unchanged in all investigated tissues, except for the 2‐fold increase in the total amount of IRS‐1 in the periepididymal adipose tissue. Therefore, the known age‐related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.     

Effects of weight loss on insulin sensitivity and arterial stiffness in overweight adults

Obesity is characterized by metabolic and vascular abnormalities. We examined the effects of weight loss on insulin sensitivity and arterial stiffness in overweight adults. Twelve (9 females; 3 males) overweight (body mass index, 30.3 +/- 3.7) adults (54.9 +/- 3.9 years) without diabetes or vascular disease were counseled by a registered dietician to lose weight over 6 months. Vascular structure, function, and wall mechanical properties were measured via ultrasound. Intravenous glucose tolerance test, 24-hour blood pressure, body composition (dual-energy x-ray absorptiometry), and lipids were also assessed. There were significant reductions in body mass (86.3 +/- 14.2 vs 79.5 +/- 13.8 kg, P < .0001) and percentage of fat (44.3% +/- 7.0% vs 41.0% +/- 8.5%, P < .01) after weight loss. There were significant improvements in total cholesterol (6.0 +/- 0.9 vs 5.0 +/- 0.8 mmol/L, P < .0001), low-density lipoprotein cholesterol (3.9 +/- 0.7 vs 3.2 +/- 0.6 mmol/L, P < .0001), triglycerides (3.4 +/- 2.3 vs 2.4 +/- 0.9 mmol/L, P < .05), and insulin sensitivity (3.3 +/- 1.7 vs 5.4 +/- 1.6 microU x 10(-4) min(-1) mL(-1), P < .0001) after weight loss. Brachial artery compliance (P < .05) and distensibility (P < .05) curves over the physiologic pressure range improved, whereas endothelial function and intima-media thickness remained unchanged. In overweight adults, 6 months of weight loss resulted in improvements in body composition, insulin sensitivity, lipid profile, and brachial artery compliance and distensibility.     

Beta-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults

CONTEXT: Type 2 diabetes mellitus (T2DM) is estimated to account for 10-45% of incident pediatric diabetes cases. OBJECTIVE: Our objective was to characterize the metabolic defects underlying T2DM in adolescents and young adults. DESIGN, SETTING, AND PATIENTS: We conducted a cross-sectional study of islet function and insulin sensitivity in 16 adolescents with T2DM and 13 obese (OB) and 13 lean (LN) age-matched nondiabetic subjects at a University Medical Center. INTERVENTION: We provided oral and iv glucose tolerance tests. MAIN OUTCOME MEASURES: We measured insulin and glucagon levels, insulin sensitivity, acute insulin responses to iv glucose, and the ratio of proinsulin to immunoreactive insulin. RESULTS: The diabetic subjects had elevated fasting insulin levels and significantly reduced insulin sensitivity (P < 0.05). The acute insulin response to iv glucose was comparable in the T2DM and LN groups (P < 0.05 for the OB vs. LN and T2DM), but insulin secretion adjusted for insulin resistance, the disposition index, was severely impaired in the diabetic subjects (P < 0.05 for the T2DM vs. LN and OB). The ratio of proinsulin to immunoreactive insulin did not differ among the three groups in the basal or stimulated state. Plasma glucagon levels were comparable before and after ingestion of glucose. CONCLUSIONS: These findings demonstrate that diabetic adolescents have significant insulin resistance, even compared with subjects of similar obesity and body fatness, and impaired insulin secretion relative to their degree of insulin resistance. However, the adolescent diabetic subjects retained a first-phase insulin response to glucose that was comparable to lean controls and did not have hyperproinsulinemia or hyperglucagonemia.     

Effects of a multidisciplinary weight loss intervention on body composition in obese adolescents

OBJECTIVE: To investigate if a multidisciplinary weight loss program in adolescents suffering severe obesity allows adequate growth and development and avoid lean mass loss. DESIGN: A total of 55 adolescents (33 girls and 22 boys) suffering severe obesity were enrolled in an interdisciplinary weight reduction program lasting 6-12 months. Progressive submaximal physical activity was performed and national dietary allowances for adolescents with low levels of physical activity energy were provided. MEASUREMENTS: Total and segmental body composition was assessed by means of dual-energy X-ray absorptiometry. RESULTS: The mean height significantly increased (P<0.001). The mean body mass index (BMI) dropped in boys from 34.5+/-3.2 to 25.5+/-2.3 kg/m(2) and in girls from 38.4+/-4.1 to 28.4+/-4.1 kg/m(2). Height increased according to the expected pattern (P<0.001). Total lean mass (LM) did not vary and was positively correlated to pubertal development in both sexes before and after weight loss. Steepest drop in fat mass (FM) was observed in the trunk (-63.2+/-10.1% in boys and -51.5+/-11.4% in girls). Decrease in BMI and FM was tightly correlated in both sexes. However, slopes significantly differed (P<0.0005) so that a decrease of 1 kg/m(2) in BMI corresponded to a decrease of 3.92 kg in FM in girls and of 5.44 kg in boys. In each sex, FM at baseline and duration of the treatment were the main determinants of the decrease in FM. CONCLUSION: During adolescence, despite a major weight loss, adequate growth and preservation of LM can be achieved. Weight loss kinetics markedly differs between boys and girls. Low-calorie diets are unnecessary to achieve a marked reduction of severe obesity during puberty.     

Hepatic insulin clearance increases after weight loss in obese children and adolescents.

BACKGROUND: Obesity is a rapidly increasing health problem among US youth. Hyperinsulinemia is associated with obesity and has been found to be a contributory factor for the development of cardiovascular disease in the obese. It has been suggested that hyperinsulinemia of obesity is a result of increased insulin secretion caused by insulin resistance. However, it has been shown in adults that decreased hepatic insulin clearance (HIC) is the primary cause of hyperinsulinemia in this population. METHODS: We studied 15 obese children and adolescents (11 F, 4 M; 8.6 to 18.1 years) before and 10 weeks after their enrollment in a multidisciplinary weight reduction program, which included a protein-sparing modified fast, a moderate intensity progressive exercise program, and a behavior-modification intervention. RESULTS: All patients lost weight (P < 0.05). Measurements of immunoreactive insulin (IRI) and C-peptide reactivity (CPR) were performed before the program and at 10 weeks. IRI levels dropped significantly, whereas CPR levels did not change. CPR/IRI molar ratios, considered an indirect estimation of HIC, rose significantly after weight loss. CONCLUSIONS: Our data suggest that hyperinsulinemia seen in obese children and adolescents is caused by decreased HIC. The cause for this decrease remains unknown, but it is reversible upon weight loss.     

Changes in fat-free mass in obese subjects after weight loss: a comparison of body composition measures.

Estimates of body composition by densitometry were made in 84 apparently healthy subjects (42 men, 42 women) with a mean age of 40 +/- 6 years (mean +/- s.d.), before and after weight loss. The initial body mass index (BMI) was 30.7 +/- 2.3 kg/m2 and the achieved weight loss on a 4.2 MJ/day energy deficit diet for 13 weeks was 12.2 +/- 3.7 kg. The results by densitometry were compared with estimates obtained by four other techniques: deuterium oxide dilution, skinfold thickness, bioelectrical impedance (three equations) and BMI (two equations). The fat-free mass (FFM) loss estimated by densitometry in men and women was 2.8 +/- 1.8 kg and 1.3 +/- 1.3 kg respectively. The dilution technique gave comparable results with densitometry. The losses of FFM assessed by skinfold thicknesses, BMI and impedance equations were almost similar, but significantly larger than the reduction in FFM measured by densitometry. These deviations were mainly the result of significantly larger differences from densitometry before compared to after weight loss. No correlation was found between change in FFM by densitometry and change in resistance measured by the bioelectrical impedance method in both sexes. It is concluded that application of published prediction formulae in weight loss studies are less appropriate and will lead to changes in FFM that are significantly different from the changes estimated by densitometry or deuterium oxide dilution.     

Secretion and hepatic extraction of insulin after weight loss in obese noninsulin-dependent diabetes mellitus

We assessed the effects of weight loss on pancreatic secretion and hepatic extraction of insulin in 11 obese subjects with noninsulin-dependent diabetes mellitus. Weight loss of 15.4 +/- 2.0 kg (mean +/- SE) resulted in decreased fasting insulin [20.2 +/- 2.5 to 9.8 +/- 2.5 microU/mL (145 +/- 18 to 70 +/- 18 pmol/L); P less than 0.02] and C-peptide (850 +/- 80 to 630 +/- 110 pmol/L; P less than 0.05) levels. The plasma glucose response to oral glucose and iv glucagon was improved with unchanged peripheral insulin levels. When plasma glucose levels were matched to those before weight loss, peripheral serum insulin and plasma C-peptide responses to iv glucagon were increased and similar to those in obese nondiabetic subjects studied at euglycemia. The total insulin response (area under the curve) to iv glucagon was reduced 30% (P less than 0.005), while the total C-peptide response area did not change after weight loss. At matched hyperglycemia, the total response area was enhanced 72% for insulin (P less than 0.002) and 64% for C-peptide (P less than 0.001). Incremental (above basal) response areas after weight loss did not change for insulin, but increased 66% for C-peptide (P less than 0.05). The incremental areas were augmented nearly 2-fold (196%) for insulin (P less than 0.01) and 1.7-fold (173%) for C-peptide (P less than 0.01) when assessed at matched hyperglycemia. Both basal (7.3 +/- 0.5 to 14.1 +/- 1.8; P less than 0.01) and total stimulated (6.1 +/- 0.4 to 8.8 +/- 1.4; P less than 0.05) C-peptide to insulin molar ratios increased after weight loss. We conclude that after weight loss in noninsulin-dependent diabetes mellitus, 1) insulin secretion is decreased in the basal state but increased after stimulation; 2) changes in insulin secretion are reflected by peripheral levels of C-peptide but not insulin, due in part to enhanced hepatic insulin extraction; and 3) at matched levels of hyperglycemia insulin secretion is markedly increased and similar to that in obese nondiabetic subjects studied at euglycemia.     

Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children

OBJECTIVE: To study the relationships between leptin, soluble leptin receptor (sOB-R), and insulin resistance in obese children before and after weight reduction. METHODS: We determined fasting serum leptin, sOB-R, and insulin resistance index (Homeostasis model assessment (HOMA)) in 36 obese children at baseline and 1 y later and compared them to 72 lean children matched for age, gender, and pubertal stage. The changes of leptin (Deltaleptin) and sOB-R (DeltasOB-R) over the 1 y period were correlated to the changes of HOMA (DeltaHOMA), the changes of weight status, and the changes of percentage body fat (Delta%BF) based on skinfold measurements. Multiple linear regression analyses were conducted for the dependent variables Deltaleptin and DeltasOB-R, including DeltaBMI and DeltaHOMA as independent variables adjusted for age, gender, and pubertal stage. Changes of leptin and sOB-R levels were analyzed in 11 obese children after they had lost weight substantially (decrease SDS-BMI>0.5) and compared to 11 obese children without substantial weight loss matched for age, gender, and pubertal stage. RESULTS: Obese children showed significantly (P<0.001) higher leptin and lower sOB-R levels. Deltaleptin correlated significantly to DeltaSDS-BMI (r=0.28, P<0.05), Delta%BF (r=0.44, P<0.05), and DeltaHOMA (r=0.42, P<0.01), while DeltasOB-R correlated significantly to DeltaSDS-BMI (r=-0.42, P<0.01) and Delta%BF (r=-0.47, P<0.01), but not to DeltaHOMA. In contrast to DeltasOB-R, Deltaleptin correlated significantly to DeltaHOMA (P=0.02) in multiple linear regression analysis. Substantial weight loss led to a significant increase in sOB-R (P=0.02) and to a decrease in HOMA (P=0.02). In children without substantial weight loss, there were no changes in sOB-R, while HOMA (P=0.04) and leptin (P=0.02) increased significantly. CONCLUSIONS: The decrease of sOB-R and the increase of leptin levels in obese children normalized after weight loss. Therefore, these changes are consequences rather than the cause of overweight. In contrast to sOB-R, leptin levels are associated with insulin resistance.     

The effects of two different hypocaloric diets on glucagon-like peptide 1 in obese adults, relation with insulin response after weight loss

ObjectiveFew studies have investigated the effect of type of diets on GLP-1 concentrations. The aim of this study was to compare the effect of two diets on circulating GLP-1 levels and the relation with insulin response after weight loss.MethodsA population of 118 obese patients were analyzed. Patients were randomly allocated to two groups: (a) Diet I (low carbohydrate) and (b) Diet II (low fat). Biochemical and anthropometric parameters were measured before and after 3 months of hypocaloric diet.ResultsFifty-two patients (12 male/40 female) were treated with Diet I and 66 patients (21 male/45 female) with Diet II. In Group I, basal GLP-1 levels did not change after dietary treatment (9.4±3.3 vs. 9.9±3.1 ng/ml; ns). In Group II, GLP-1 levels decreased significantly (8.4%) (9.2±3.3 vs 8.7±3.1 ng/ml; P<.05). In the multivariate analysis with a dependent variable (levels of GLP-1), only insulin levels remained as an independent predictor in the model (F=5.9; P<.05), with an increase of 0.6 ng/ml (95% CI 0.1–1.1) GLP-1 concentrations with each increase of 1 mUI/ml of insulin.ConclusionA hypocaloric diet with a low fat percentage decreased GLP-1 levels with a direct correlation with insulin levels. Nevertheless, patients with a hypocaloric diet with a low carbohydrate percentage treatment did not change GLP-1 levels. Diet macronutrient manipulation on GLP-1 response could be useful in an obesity nutrition therapy.     

Moderate protein intake improves total and regional body composition and insulin sensitivity in overweight adults

A high protein intake (approximately 40% of energy intake) combined with aerobic and resistance exercise training is more closely associated with improved body composition and cardiovascular risk profile than a traditional protein intake (approximately 15% of intake) combined with moderate-intensity aerobic exercise. However, there is concern that such high-protein diets may adversely affect health. We therefore tested the hypothesis that moderate protein intake (approximately 25% of energy intake) would elicit similar benefits on body composition and metabolic profile as high protein intake. Twenty-four overweight/obese men and women (body mass index [BMI] = 32.2 +/- 3.4, percentage of body fat [%BF] = 37.3 +/- 8.0) were matched for BMI and %BF and randomly assigned to one of 3 groups for a 3-month nutrition/exercise training intervention: (1) high-protein diet (approximately 40% of energy intake) and combined high-intensity resistance and cardiovascular training (HPEx, n = 8, 5 female and 3 male), (2) moderate-protein diet (approximately 25% of energy intake) and combined high-intensity resistance and cardiovascular training (MPEx, n = 8, 5 female and 3 male), or (3) high-protein diet only (HPNx, n = 8, 5 female and 3 male). Total and regional body composition (dual-energy x-ray absorptiometry), insulin sensitivity (insulin sensitivity index to the oral glucose tolerance test), insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), IGF binding protein-3 (IGFBP-3), and blood lipids were measured at baseline and after the intervention. All groups experienced significant (P < .05) and similar losses of body weight, BMI, and total and abdominal %BF, and similar improvements in insulin sensitivity (HPEx, 6.3 +/- 1.2 vs 9.5 +/- 0.98; MPEx, 6.2 +/- 1.4 vs 8.4 +/- 1.6; HPNx, 3.7 +/- 1.1 vs 7.0 +/- 1.1; insulin sensitivity index to the oral glucose tolerance test; P < .05) and leptin levels. Furthermore, the HPEx group demonstrated decreases in total cholesterol (TC) and triglycerides, and increases in IGF-1 and IGFBP-1. The MPEx group experienced decreases in TC, whereas the HPNx group had increases in high-density lipoprotein cholesterol, TC to high-density lipoprotein, IGF-1, and IGFBP-1. In conclusion, moderate protein intake elicits similar benefits in body composition and insulin sensitivity as a high-protein diet. These findings may have practical implications for individuals interested in diets containing elevated dietary protein.     

Effect of weight loss on glucose disposal in obese and obese diabetic patients

The purpose of the study was to examine the effect of short-term weight loss on glucose disposal and lipid oxidation in obese patients. Twenty-six obese patients were divided into three groups according to their degree of glucose intolerance: normal glucose tolerance = Gp I; impaired glucose tolerance without diabetes = Gp II; diabetes = Gp III. The patients submitted to an hypocaloric, high-protein diet for 8 to 45 weeks. Respiratory exchange measurements were performed by means of continuous indirect calorimetry during a 100 g, 3 h oral glucose tolerance test (OGTT) before weight loss and were repeated at the end of the weight loss period, 3 to 8 weeks after the reintroduction of a balanced isocaloric diet. Glucose tolerance, which was decreased in Gps II and III, improved after weight loss. Glucose oxidation, which was decreased in Gps II and III showed improvement after weight reduction in both Gp II (30.9 +/- 2.3 after weight loss vs 24.2 +/- 2.0 g/3 h before, P less than 0.025) and in Gp III (33.1 +/- 1.6 vs 25.8 +/- 4.1, ns). In the diabetic group (Gp III), before weight loss, a decrease in nonoxidative glucose uptake was observed, which was probably due both to a decrease in glucose storage and to the inhibition of splanchnic glucose output. After weight loss, it increased significantly from 27.7 +/- 5.2 to 56.9 +/- 2.3 g/3 h (P less than 0.001). Postabsorptive plasma insulin levels decreased in all groups following weight reduction. When exaggerated the insulin response to the glucose load fell to normal values whereas the insulin response increased in the diabetic patients in whom it was initially blunted. Lipid oxidation rates, both preload and postload, were markedly elevated before weight loss in all three groups. They were substantially reduced after weight loss. This study shows that a weight loss of 10 to 33 kg in obese patients promoted an increase in the subnormal glucose oxidation rate in Gp II as well as an improvement of the low nonoxidative glucose uptake in the diabetic group, thus improving their glucose tolerance. There was a simultaneous reduction in lipid oxidation in both groups. Furthermore, the insulin response to the glucose load, whether elevated or decreased before weight loss, tended towards normalization after weight reduction.     

Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls

The aim of this study was to examine the effect of aerobic exercise training on insulin sensitivity in overweight and obese girls. Nineteen overweight and obese girls (mean +/- SD: age, 13.1+/-1.8 years; body mass index, 26.8+/-3.9 kg/m(2)) volunteered for this study. Body composition (dual-energy x-ray absorptiometry), insulin sensitivity (oral glucose tolerance test and homeostasis model assessment estimate of insulin resistance; n=15), adiponectin, C-reactive protein (CRP), interleukin (IL) 6, insulin-like growth factor-1, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 serum levels, and blood lipids and lipoproteins were assessed before and after 12 weeks of aerobic training. Cardiorespiratory fitness increased by 18.8% (P<.05) as a result of training. The area under the insulin concentration curve (insulin area under the curve) decreased by 23.3% (12781.7+/-7454.2 vs 9799.0+/-4918.6 microU.min/mL before and after intervention, respectively; P=.03). Insulin sensitivity was improved without changes in body weight (pre-intervention, 67.9+/-14.5 kg; post-intervention, 68.3+/-14.0 kg) or percent body fat (pre-intervention, 41.4% +/- 4.8%; post-intervention, 40.7%+/-5.2%). The lower limb fat-free mass increased by 6.2% (P<.01) as a result of training, and changes in lower limb fat-free mass were correlated with changes in the insulin area under the curve (r= -.68; P< .01). Serum adiponectin, IL-6, and CRP concentrations did not change (pre-intervention vs post-intervention: adiponectin, 9.57+/-3.01 vs 9.08+/-2.32 microg/mL; IL-6, 1.67+/-1.29 vs 1.65+/-1.25 pg/mL, CRP, 3.21+/-2.48 vs 2.73+/-1.88 mg/L) whereas insulin-like growth factor-1 was lower after training (pre-intervention, 453.8 +/- 159.3 ng/mL; post-intervention, 403.2+/- 155.1 ng/mL; P<.05). In conclusion, 12 weeks of aerobic training improved insulin sensitivity in overweight and obese girls without change in body weight, percent body fat, and circulating concentrations of adiponectin, IL-6, CRP, and other inflammatory markers. These findings suggest that increased physical activity may ameliorate the metabolic abnormalities associated with obesity in children with a mechanism other than the parameters cited earlier.     

Modest weight loss improves insulin action in obese African Americans

OBJECTIVE: We have previously shown that short-term energy restriction followed by modest lifestyle changes improves glucose tolerance for up to 1 year in obese individuals. The purpose of the present study was to determine the mechanism by which improvements in glucose tolerance occur in obese African Americans with insulin resistance and abnormal glucose tolerance. RESEARCH DESIGN AND METHODS: Nine subjects (53 +/- 2 years; body mass index, 37 +/- 3 kg/m 2 [mean +/- SEM]) received a low-energy diet (3883 +/- 222 kJ/d) for 1 week, and then followed a modest lifestyle intervention program for up to 1 year. Body composition was estimated by hydrostatic weighing, and insulin secretion and action were assessed during a hyperglycemic clamp with superimposed arginine infusion and fat meal. Baseline and final tests were performed during weight stability. RESULTS: Significant improvements ( P < .05) were observed for body weight (-6.1 +/- 1.1 kg), body composition (-5.5 +/- 1.3 kg fat mass), fasting plasma glucose (-1.1 +/- 0.3 mmol/L), fasting insulin (-52 +/- 21 pmol/L), oral glucose tolerance, and insulin action (+24%), defined as an increase in glucose disposal rate relative to plasma insulin concentration during the hyperglycemic clamp. These improvements were independent of an acute effect of energy restriction or weight loss, because body weight was stable. CONCLUSIONS: These results suggest that the improvements in glucose tolerance with a modest lifestyle intervention were attributable to an improvement in insulin action, and provide evidence that despite persistent obesity (body mass index, 34.7 +/- 2.4 kg/m 2 ), long-term benefits can be achieved with relatively small weight loss in obese African Americans.