androstane-3-17-diol-glucuronide and Insulin-Resistance

We examined interaction of sex steroid hormones and obesity with regard to insulin resistance (IR) and type 2 diabetes (T2D) by using nationally representative data from the US.. Data of 1461 men aged ≥20years who participated in the Third National Health and Nutrition Examination Survey were analyzed. Multiplicative interaction was calculated by cross-product interaction terms in multivariable logistic regression models. Additive interaction was assessed by the relative excess risk due to interaction (RERI).. After adjusting for demographic and lifestyle covariates, the odds of IR were greatest among obese men with low free testosterone and high androstanediol glucuronide. Multiplicative interactions for total testosterone, free testosterone, and free estradiol index (FEI) were statistically significant with central obesity but not with overweight and obesity regarding to T2D (P<0.05). Significant additive interactions with obesity or central obesity were detected for total testosterone (RERI=2.75, 95% CI=0.92,4.59), SHBG (RERI=5.71, 95% CI=0.77,10.64), and FEI (RERI=-9.96, 95% CI=-19.18,-0.74) with regard to IR, beta-cell dysfunction, and T2D.. Our findings add to the evidence suggesting that low testosterone and high estradiol may be associated greater risks of IR and T2D by interacting with overall and central obesity in adult men.

Topics: Adult; Aged; Androstane-3,17-diol; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Estradiol; Humans; Insulin Resistance; Logistic Models; Male; Middle Aged; Nutrition Surveys; Obesity; Obesity, Abdominal; Overweight; Prevalence; Risk; Testosterone; United States; Waist Circumference; Young Adult

To determine whether hyperinsulinemia can directly reduce serum sex hormone-binding globulin (SHBG) levels in obese women with the polycystic ovary syndrome, six obese women with this disorder were studied. Before study, ovarian steroid production was suppressed in each woman by the administration of 7.5 mg of a long-acting GnRH agonist, leuprolide depot, im, on days -56, -28, and 0. This resulted in substantial reductions in serum concentrations of testosterone (from 1.72 +/- 0.29 nmol/L on day -56 to 0.32 +/- 0.09 nmol/L on day 0), non-SHBG-bound testosterone (from 104 +/- 16 pmol/L on day -56 to 19 +/- 5 pmol/L on day 0), androstenedione (from 7.25 +/- 1.65 nmol/L on day -56 to 2.78 +/- 0.94 nmol/L on day 0), estrone (from 371 +/- 71 pmol/L on day -56 to 156 +/- 29 pmol/L on day 0), estradiol (from 235 +/- 26 pmol/L on day -56 to 90 +/- 24 pmol/L on day 0), and progesterone (from 0.28 +/- 0.12 nmol/L on day -56 to 0.08 +/- 0.02 nmol/L on day 0). Serum SHBG levels, however, did not change (18.8 +/- 2.8 nmol/L on day -56 vs. 17.8 +/- 2.6 nmol/L on day 0). While continuing leuprolide treatment, the women were administered oral diazoxide (300 mg/day) for 10 days to suppress serum insulin levels. Diazoxide treatment resulted in suppressed insulin release during a 100-g oral glucose tolerance test (insulin area under the curve, 262 +/- 55 nmol/min.L on day 0 vs. 102 +/- 33 nmol/min.L on day 10; P less than 0.05) and deterioration of glucose tolerance. Serum testosterone, androstenedione, estrone, estradiol, and progesterone levels did not change during combined diazoxide and leuprolide treatment. In contrast, serum SHBG levels rose by 32% from 17.8 +/- 2.6 nmol/L on day 0 to 23.5 +/- 2.0 nmol/L on day 10 (P less than 0.003). Due primarily to the rise in serum SHBG levels, serum non-SHBG-bound testosterone levels fell by 43% from 19 +/- 5 pmol/L on day 0 to 11 +/- 4 pmol/L on day 10 (P = 0.05). These observations suggest that hyperinsulinemia directly reduces serum SHBG levels in obese women with the polycystic ovary syndrome independently of any effect on serum sex steroids.

Topics: Adult; Androstane-3,17-diol; Androstenedione; Diazoxide; Estradiol; Estrone; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Insulin; Insulin Resistance; Leuprolide; Obesity; Polycystic Ovary Syndrome; Progesterone; Sex Hormone-Binding Globulin; Testosterone