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An increase in androgenicity may contribute to the development of insulin resistance in postmenopausal women. Increased androgenicity in women has been found to be associated with the development of type 2 diabetes. In addition, obesity and central obesity are associated with greater androgenicity. Insulin sensitivity, androgenicity, and body composition were characterized in 34 nondiabetic postmenopausal women age 72 +/- 1 years (mean +/- SEM) to test the hypothesis that androgenicity is a predictor of insulin sensitivity independent of measures of obesity. Androgenicity was measured using levels of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and free androgen index (FAI). Insulin sensitivity (S(I)) was determined from a frequently sampled intravenous glucose tolerance test. Body composition measures included body mass index (BMI) and dual energy x-ray absorptiometry measurements of total and central fat mass. S(I) was found to be associated with total fat mass (r = -.51, P =.002), central fat mass (r = -.62, P =.0001), BMI (r = -.55, P =.0008), SHBG levels (r =.65, P =.0001), and FAI (r = -.41, P =.01). SHBG levels were inversely correlated with central fat mass (r = -.59, P =.0002). Using multiple regression, SHBG and central fat mass were the only significant independent predictors of S(I), accounting for 50% of its variance (r =.71, P =.0001); total fat mass, BMI, total and free testosterone, DHEA-S, androstenedione, and FAI did not enter the model. We conclude that there is a significant association between insulin sensitivity and androgenicity in postmenopausal women that is independent of obesity. Interventions to decrease androgenicity may therefore be useful in improving insulin sensitivity in postmenopausal women.

The purpose of the present study was to determine if the improvement in insulin sensitivity after resistance training (RT) is associated with a decline in plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptor 1 (sTNF R1), and soluble TNF receptor 2 (sTNF R2). Eleven older hypertensives (5 men/6 women, 67 +/- 2 years) participated in a 4-month RT program. Following RT there was a significant increase in upper body (P =.029) and lower body strength (P =.001), assessed by the bench press 1-repetition maximum (1RM) and leg press 1RM, respectively. The RT program produced a significant increase in lean body mass (LBM) (P =.029), a trend for a decline in percent body fat (P =.083), and no change in total body mass (P =.958). Insulin-mediated glucose disposal, assessed by the hyperinsulinemic euglycemic clamp procedure, significantly increased following RT (P =.026). Despite the increase in insulin action, plasma levels of TNF-alpha, sTNF R1, and sTNF R2 were not significantly altered by RT (TNF-alpha: P =.118, sTNF R1: P =.184, sTNF R2: P =.168). In conclusion, a 4-month RT program significantly increased insulin-mediated glucose disposal and LBM without a significant reduction in plasma levels of TNF-alpha, sTNF R1, and sTNF R2 in older hypertensive subjects.

The purpose of the present study was to determine if the improvement in insulin sensitivity following aerobic exercise training (AEX) is associated with a decline in plasma tumor necrosis factor-alpha (TNF-alpha) levels. Fourteen older hypertensive females (age, 62 +/- 2 years) participated in a 6-month AEX program. Following AEX there was a significant increase in maximal aerobic capacity (VO(2)max) (P =.0001), and a significant decline in systolic (P =.01) and diastolic (P =.006) blood pressure. In addition, following AEX there was a significant decline in total body fat mass (P =.005), abdominal fat mass (P =.048), and percent body fat (P =.006). Insulin sensitivity, as assessed by the insulin-assisted frequently sampled intravenous glucose tolerance test (FSIVGTT), increased significantly following AEX (P =.007). Despite the increase in insulin sensitivity and the decline in body fat, plasma TNF-alpha levels were not altered by AEX (P =.223). No significant relationship existed among the changes in TNF-alpha levels and the changes insulin sensitivity or any measure of body composition following AEX. In conclusion, in this population of older hypertensive females, AEX improved insulin sensitivity and lowered blood pressure without a reduction in plasma TNF-alpha levels., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Adrenergic responsiveness (AR) appears to be increased in subjects with diabetes, but measurement of arterial AR in normotensive people with type 2 diabetes mellitus has not been previously reported. We sought to determine whether, compared with control subjects, there is increased arterial AR in type 2 diabetes mellitus and its relationship to the level of systemic sympathetic nervous system activity (SNSa). We studied 15 type 2 diabetic subjects aged 57 +/- 3 years without hypertension or clinical signs of autonomic neuropathy and 13 age-matched control subjects aged 55 +/- 2 years. We assessed vascular alpha-AR by measuring forearm blood flow (FABF) by venous occlusion plethysmography during intrabrachial artery norepinephrine (NE) and phentolamine infusions, as well as arterial plasma NE levels and the extravascular NE release rate (NE2) derived from 3H-NE kinetics, as estimates of systemic SNSa. The vasoconstricting effect of NE during intrabrachial artery NE infusion was greater in type 2 diabetes compared with control subjects (P = .02). The vasodilating effect of phentolamine was greater in type 2 diabetics compared with control subjects (P = .05), suggesting increased endogenous arterial alpha-adrenergic tone. Arterial plasma NE levels (control v type 2, 1.8 +/- 0.10 v 1.84 +/- 0.14 nmol/L, P = .86) and NE2 (control vtype 2, 11.8 +/- 1.54 v 13.3 +/- 0.89 nmol/min/m2, P = .39) were similar in the two groups. In summary, in type 2 diabetes compared with control subjects, (1) the vasoconstriction response to intraarterial NE is greater, (2) plasma NE and NE2 are similar, suggesting similar levels of systemic SNSa, and (3) arterial alpha-adrenergic tone is greater. We conclude that subjects with type 2 diabetes demonstrate inappropriately increased alpha-AR for their level of systemic SNSa.

Several lines of evidence support peripheral nerve ischemia as a contributing factor in the etiology of human diabetic neuropathy. We questioned whether diabetic subjects with relatively normal nerve function in the baseline state would be more likely than healthy control subjects to show either improvement of ulnar nerve function with acute intraarterial infusion of nitroprusside (vasodilation) or be more sensitive than control subjects to worsening of nerve function with acute intraarterial infusion of norepinephrine (vasoconstriction). We measured forearm blood flow (FABF) using venous occlusion plethysmography and assessed ulnar nerve function at baseline and during two intrabrachial artery infusions. Six nondiabetic control subjects (mean age, 56 years) and 11 subjects with type 2 diabetes (mean age, 58 years) in good general health participated. Only three type 2 diabetic subjects had peripheral sensory neuropathy, which was mild. Among control subjects, there was no significant change in sensory distal latency, motor distal latency, motor proximal latency, or sensory or motor conduction velocity during norepinephrine infusion. In contrast, among type 2 diabetic subjects, there was a significant increase in sensory (baseline vnorepinephrine, 2.73+/-0.10 v 2.94+/-0.10 milliseconds [MS], P< or =.01) and motor distal latencies (baseline v norepinephrine, 2.90+/-0.06 v 3.18+/-0.1 ms, P< or =.001) and motor proximal latency (baseline v norepinephrine, 7.15+/-0.18 v 7.60+/-0.23 ms, P<.01) and a decrease in sensory conduction velocity (baseline v norepinephrine, 52.1+/-2.0 v 47.7+/-1.6 m/s, P<.01) during norepinephrine infusion. There were no consistent changes in nerve function during nitroprusside infusion in either group. In summary, we found that subjects with type 2 diabetes, but not control subjects, demonstrate a decrement in nerve function with vasoconstriction during intraarterial infusion of norepinephrine, but no consistent change during nitroprusside-induced vasodilation. These findings suggest there may be enhanced sensitivity of nerve function to ischemia in type 2 diabetic subjects with mild or absent clinical neuropathy.