Insulin Sensitivity In Older Men Research Articles

Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels.

Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.

Testosterone Supplementation Improves Carbohydrate and Lipid Metabolism in Some Older Men with Abdominal Obesity.

Background/ObjectivesThe effects of testosterone supplementation on carbohydrate and lipid metabolism in obese older men are uncertain. We conducted a single-arm open-label prospective pilot study to investigate the effects of testosterone supplementation on central and peripheral insulin sensitivity in older men with upper body obesity and insulin resistance.Subjects/MethodsTwenty men (62–78 years-old) with morning testosterone levels <13.9 nmol/L (400 ng/dL), waist circumference ≥ 102 cm, and HOMA-IR ≥ 4.0 or HgbA1C 5.7–6.4% applied transdermal testosterone (10 mg) daily for 20 weeks. Insulin sensitivity (Si) was determined by a 2-stage glucose clamp, liver and intramyocellular lipid by 1H-MR spectroscopy and body composition by DEXA.ResultsTestosterone supplementation significantly reduced total fat (−.9 ± 2.4 kg, p=0.002), trunk fat (−1.3 ± 1.4 kg, p=0.0007) and extremity fat (−0.7 ± 1.1 kg, p=0.01), and increased extremity lean tissue (+1.3 ± 1.4 kg, p=0.0006). Whole body (WB) Si improved by 21% (0.76 ± 1.57 dL/min per µU/mL, p=0.04) and insulin-stimulated glucose uptake (Rd) by 24% (0.91 ± 1.74 dL/min per µU/mL, p=0.03). Improvements in glucose kinetics were limited to men with reductions in trunk and extremity fat greater than median declines for the entire group. Reductions in intramyocellular lipid were associated with improvements in WB Si (p=0.04) and Rd (p=0.03). Change in Rd accounted for 90% of the change in WB Si. Hepatic glucose output and liver lipid/H2O were unchanged (p>0.05). Multivariable analyses revealed that reductions in extremity fat, trunk fat, and FFA levels during the clamp accounted for 45% (p=0.004), 31% (p=0.002) and 8% (p=0.04) of respective changes in Rd. Triglycerides decreased by −0.40 ± 0.67mmol/L (p=0.02), LDL-C by-0.35 ± 0.57 mmol/L (p=0.02), and HDL-C by −0.14 ± 0.19 mmol/L (p=0.004).ConclusionsTestosterone supplementation that resulted in greater reductions in regional adiposity was associated with improved insulin sensitivity, lower LDL-C and fasting triglycerides, but lower HDL-C. Placebo controlled trials need to further examine the potential cardiometabolic risks/benefits of androgen supplementation for older men with low testosterone levels, central obesity, and insulin resistance.

Sex differences in insulin action and body fat distribution in overweight and obese middle-aged and older men and women.

Controversy exists as to whether there are differences in insulin action between older men and women, and what factors contribute to these differences. This study tests the hypothesis that sex differences in regional fat distribution contribute to a disparity in insulin sensitivity in older men vs. older women. Healthy, older (50-71 years), sedentary men (n = 28) and women (n = 29) were recruited to participate in the study. Body fat, fat-free mass (FFM), and visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue areas were measured by DXA and computed tomography (CT). For measurements of insulin-stimulated glucose disposal (M), insulin was infused at a constant rate of 240 pmol.m(-2).min(-1), and M was calculated between the 90th and 120th min of the hyperinsulinemic-euglycemic clamp. The men weighed 16% more and had 16% higher waist and 4% lower hip circumferences than women (p < 0.05 for all). Total fat mass and SAT were 21% and 33% lower and FFM was 49% higher in men than in women, whereas waist-to-hip ratio (WHR) and VAT:SAT ratio were 21% and 56% higher in men than in women (p < 0.05 for all). Although insulin concentrations during the glucose clamp were higher in men, M was 47% lower in men vs. women (21.7 +/- 1.1 vs. 46.7 +/- 3.1 micromol.L(-1).kg FFM(-1).min(-1), p < 0.05). The sex-related differences in M persisted after controlling for insulin concentrations during the glucose clamp, for waist, WHR, and VAT:SAT. Older men are more insulin resistant than women, despite lower body fat and subcutaneous abdominal fat. This difference in insulin sensitivity is not explained by abdominal fat distribution, therefore other metabolic factors contribute to the sex differences in insulin sensitivity.

Abdominal Adiposity Assessed by Dual Energy X-Ray Absorptiometry Provides a Sex-Independent Predictor of Insulin Sensitivity in Older Adults

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. 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. 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. 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.

Twice-Weekly Progressive Resistance Training Decreases Abdominal Fat and Improves Insulin Sensitivity in Older Men With Type 2 Diabetes

To evaluate the influence of a twice-weekly progressive resistance training (PRT) program, without a concomitant weight loss diet, on abdominal fat and insulin sensitivity in older men with type 2 diabetes. Nine older men (aged 66.6 +/- 3.1) with type 2 diabetes participated in a 16-week PRT supervised program (50-80% of the one repetition maximum), for all main muscle groups. Basal glycemia, HbA(1c), diet, habitual physical activity, body composition, and upper/lower maximal strength were measured. Insulin sensitivity was determined according to Bergman's minimal model procedure and abdominal fat was obtained by computed tomography. The measurements were taken 4 weeks before training (-4), immediately before training (0), and at 8-week intervals (i.e., weeks 8 and 16) during the 16-week training period. No significant variation was observed in any of the above selected parameters during the 4-week control period. After PRT, both leg and arm maximal strength increased significantly by 17.1 and 18.2%, respectively. Visceral and subcutaneous abdominal fat decreased significantly by 10.3% (from 249.5 +/- 97.9 to 225.6 +/- 96.6 cm(3), P < 0.01) and by 11.2% (from 356.0 +/- 127.5 to 308.6 +/- 118.8 cm(3), P < 0.01), respectively, while no changes were observed in body mass. PRT significantly increased insulin sensitivity by 46.3% (from 2.0 +/- 1.2 to 2.8 +/- 1.6 . 10(4) . min(-1) . muU(-1) . ml(-1), P < 0.01), whereas it significantly decreased (-7.1%, P < 0.05) fasting blood glucose (from 146.6 +/- 28.3 to 135.0 +/- 29.3 mg/dl). Finally, a 15.5% increase in energy intake (from 2,287.1 +/- 354.7 to 2,619.0 +/- 472.1 kcal/day, P < 0.05) was observed. Two sessions per week of PRT, without a concomitant weight loss diet, significantly improves insulin sensitivity and fasting glycemia and decreases abdominal fat in older men with type 2 diabetes.