Osama Hamdy

OBJECTIVE: The objective was to examine prospectively the association between low testosterone and sex hormone-binding globulin (SHBG) levels and the subsequent development of type 2 diabetes in men. RESEARCH DESIGN AND METHODS: Analyses were conducted on the cohort of the Massachusetts Male Aging Study, a population-based random sample of men aged 40-70. Of the 1,709 men enrolled in 1987-1989 (T1), 1,156 were followed up 7-10 years later (T2). Testosterone and SHBG levels at T1 were used to predict new cases of diabetes between T1 and T2. RESULTS: After controlling for potential confounders, diabetes at follow-up was predicted jointly and independently by lower baseline levels of free testosterone and SHBG. The odds ratio for future diabetes was 1.58 for a decrease of 1SD in free testosterone (4 ng/dl) and 1.89 for a 1SD decrease in SHBG (16 nmol/l), both significant at P < 0.02. CONCLUSIONS: Our prospective findings are consistent with previous, mainly cross-sectional reports, suggesting that low levels of testosterone and SHBG play some role in the development of insulin resistance and subsequent type 2 diabetes.

OBJECTIVE: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. RESEARCH METHODS AND PROCEDURES: Twenty-four insulin-resistant obese subjects with varying degrees of glucose tolerance completed a 6-month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)] and highly sensitive C-reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. RESULTS: Participants had a 6.9 +/- 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 +/- 3 vs. 23.6 +/- 3 ng/mL, p = 0.01) and IL-6 (2.75 +/- 1.51 vs. 2.3 +/- 0.91 pg/mL, p = 0.012). TNF-alpha levels tended to decrease (2.3 +/- 0.2 vs. 1.9 +/- 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C-reactive protein (r = 0.466, p < 0.05). DISCUSSION: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL-6 and a tendency toward a decrease in circulating TNF-alpha, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.

OBJECTIVE: Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS. RESEARCH DESIGN AND METHODS; We studied 24 obese subjects (9 men and 15 women, age 49.3 +/- 1.9 years, BMI 36.7 +/- 0.94 kg/m(2), mean +/- SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen. RESULTS: This intervention resulted in 6.6 +/- 1% reduction in body weight (P < 0.001) and significant improvement of insulin sensitivity index (2.9 +/- 0.36 vs. 1.9 +/- 0.33 [10(-4) x min(-1) x ( microU ml(-1))], P < 0.001). FMD significantly improved (12.9 +/- 1.2% vs. 7.9 +/- 1.0%, P < 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 +/- 7.7 vs. 265.6 +/- 9.3 ng/ml, P = 0.018 and 36.2 +/- 3.6 vs. 48.6 +/- 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R(2) = 0.47, P = 0.001). CONCLUSIONS: We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance.