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The purpose of this study was to compare insulin's ability to stimulate glucose uptake in the arm and leg in a group of older hypertensive individuals (n = 13, 66 +/- 2 yr old). We also examined the effect of a 4-mo whole body resistance-training (RT) program on arm and leg glucose clearance (GC) during a hyperinsulinemic-euglycemic clamp. During the hyperinsulinemic-euglycemic clamp, GC was assessed by simultaneous measurement of arm and leg blood flow (BF) and assessment of fractional glucose extraction (GE) in blood samples from the brachial artery, brachial vein, and popliteal vein. At baseline, a significant main effect (arm vs. leg) demonstrated greater GC and BF in the arm than in the leg (P = 0.006 for GC and P = 0.012 for BF). Insulin significantly increased GE, BF, and GC in the arm and leg (main effects: P = 0.0001 for GE, P = 0.0001 for BF, and P = 0.0001 for GC) at baseline. However, the effect of insulin was similar in the arm and leg. After RT, a significant main effect (baseline vs. RT) demonstrated greater GE and GC in the leg (P = 0.024 for GE and P = 0.053 for GE), but not in the arm (P = 0.31 for GE and P = 0.14 for GC). No significant main effect (baseline vs. RT) for BF in the arm or leg was observed after RT. In conclusion, the greater GC in the arm than in the leg at baseline is primarily due to enhanced arm BF. Furthermore, whole body RT appears to increase GC in the leg but not in the arm.

Background: An increase in total adiposity and in particular an abdominal distribution of adiposity may contribute to the decline in metabolic insulin sensitivity observed in older men and women. The objective of this cross-sectional study was to determine which measure of abdominal adiposity would provide the best sex-independent predictor of metabolic insulin sensitivity in older men and women., Methods: Insulin sensitivity and abdominal adiposity were measured in healthy, nondiabetic older (64 +/- 6 years; mean +/- standard deviation) men (n = 23) and women (n = 31). Metabolic Insulin Sensitivity Index (S(I)) was determined from a frequently sampled insulin-assisted intravenous glucose tolerance test. Body fat mass and abdominal fat mass were determined from dual energy X-ray absorptiometry (DXA) scans. Anthropometric measures included waist and hip circumferences, height, and body weight., Results: Although waist circumference, waist index (waist circumference divided by height), and waist-hip ratio (WHR) were all lower in women than in men, there was no sex difference in DXA L1-L4 fat mass. In univariate analyses, S(I) was significantly inversely related with body weight, body mass index, waist circumference, waist index, percentage of total body and abdominal fat, and DXA L1-L4 fat mass but not with WHR. The DXA L1-L4 fat mass was identified as the best independent predictor of S(I), accounting for 41.2% of the variance (p <.0001) in a stepwise multiple regression model that controlled for sex., Conclusions: WHR is not associated with S(I) in either men or women. Abdominal adiposity measured by DXA L1-L4 fat mass provides a sex-independent predictor of S(I) in older men and women.

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.

Objectives: To test the hypothesis that both raloxifene and estrogen would improve insulin sensitivity in postmenopausal women and that the magnitude of the effect would be similar for both drugs., Design: Placebo-controlled, double-blind, randomized study., Setting: The General Clinical Research Center of the University of Michigan Medical Center, a university hospital., Participants: Forty-four healthy postmenopausal women 73 +/- 7 years old (mean age +/- standard deviation) who were not receiving hormone replacement therapy., Intervention: Eight weeks of drug therapy with randomization to raloxifene (n = 16), estrogen (n = 14), or placebo (n = 14)., Measurements: These subjects underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (SI) and total and regional (central) body composition measurements by dual-energy x-ray absorptiometry at baseline and after 8 weeks of drug therapy., Results: There were no statistically significant differences in age, body mass index, total or central fat mass, or SI between the three groups at baseline. The major outcome variable was SI. After 8 weeks of drug therapy, there was no significant change in SI in the placebo group or in the estrogen group and a significant decrease in SI in the raloxifene group, P =.003., Conclusion: In contrast to estrogen's ability to maintain insulin sensitivity, raloxifene decreases insulin sensitivity in healthy nondiabetic postmenopausal women. The clinical significance of this effect of raloxifene to impair insulin sensitivity in postmenopausal women warrants further evaluation in future studies.

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.)

We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the frequently sampled intravenous glucose tolerance test, was significantly (P = 0.0001) increased following AEX. In addition, there was a significant (P = 0.001) interaction between AEX and ACE genotype. S(I) increased significantly (P < 0.05) more in those with the II (2.5 +/- 0.8 microU x 10(-4) x min(-1) x ml(-1)) ACE genotype compared with both the DD and ID (0.7 +/- 0.1 and 0.7 +/- 0.2 microU x 10(-4) x min(-1) x ml(-1), respectively) ACE genotypes. Similarly, there was a significant (P = 0.036) decrease in the acute insulin response to glucose (AIR(G)) and a significant (P = 0.05) interaction between AEX and ACE genotype. AIR(G) decreased significantly (P < 0.05) more in those with the II (-17.6 +/- 5.6 mU/ml) ACE genotype compared with both the DD and ID (-1.4 +/- 6.2 and -3.6 +/- 2.5 mU/ml) ACE genotypes. In conclusion, we demonstrated that those older hypertensives with the ACE II genotype have the greatest improvement in insulin action following AEX.

Background: The purpose of this study was to determine whether age is a predictor of sensitivity to the peripheral effects of insulin on carbohydrate metabolism independent of the potential influences of the level of sympathetic nervous system (SNS) activity and blood pressure (BP)., Methods: In 60 human subjects (age range 19-78 years), insulin sensitivity, SI, was determined from glucose and insulin levels obtained during an intravenous glucose tolerance test, and plasma norepinephrine (NE) levels were measured to estimate SNS activity., Results: There were age-associated increases in plasma NE level (r = .585; p < .001) and mean arterial BP (r = .516; p < .001), and an age-associated decline in SI (r = -.352; p = .04). However, in stepwise multiple regression analysis, body mass index (BMI) and mean arterial BP were the only independent predictors of SI, accounting for 43% of the variance in SI; age, plasma NE level, plasma epinephrine level, and fasting plasma glucose did not enter the model. Although these results suggest an age-associated decline in insulin sensitivity, this decline appears to be associated with BMI and mean arterial BP rather than aging per se. In addition, the age-associated increase in SNS activity was not found to be an independent predictor of insulin sensitivity., Conclusion: This study demonstrates that in addition to BMI, blood pressure should be considered as another confounding factor in studies of insulin sensitivity in human aging.