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Sex Steroid Hormones, Upper Body Obesity, and Insulin Resistance

Center for Human Nutrition (N.A., A.G., S.M.G.), Department of Internal Medicine (N.A., A.G., S.M.G.), Division of Endocrinology and Metabolism (N.A., A.G., S.M.G.), and Division of Radiology (R.M.P.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; and Department of Internal Medicine, University of Texas Health Science Center (S.M.H.), San Antonio, Texas 78229

Address all correspondence and requests for reprints to: Nicola Abate, M.D., Center for Human Nutrition, University of Texas Southwestern Medical Center, 6011 Harry Hines Boulevard, Dallas, Texas 75390-9169. E-mail: nicola.abate{at}utsouthwestern.edu.

Abstract

Low plasma levels of SHBG and free testosterone have been associated with increased insulin resistance and risk for type 2 diabetes in males. As truncal obesity, a condition accompanied by increased insulin resistance, is also associated with low SHBG and testosterone levels, the independent association of low free testosterone and SHBG with excessive insulin resistance remains to be determined. In this study we evaluated whether in normogonadic men, plasma levels of SHBG and free testosterone are primarily related to insulin resistance or to generalized and regional adiposity. Hyperinsulinemic-euglycemic clamps and iv glucose tolerance tests were performed in 24 healthy volunteer and 33 patients with mild type 2 diabetes. The 2 groups were chosen to have similar body mass index and were found to have similar body composition and fat distribution, assessed by underwater weighing, skinfold thickness, and magnetic resonance imaging of the abdomen. In the 2 groups combined, plasma levels of SHBG correlated inversely with fat accumulation in both sc and intraabdominal areas. Plasma levels of free testosterone correlated inversely with both truncal and peripheral skinfold thickness only in the nondiabetic men. No associations between plasma levels of sex steroid hormones and insulin resistance, hepatic glucose output, or insulin secretion were found to be independent of adiposity. Furthermore, although patients with diabetes were more insulin resistant than those without diabetes, the 2 groups had similar plasma concentrations of free testosterone (55 ± 14 and 67 ± 27 pmol/liter, respectively), SHBG (19 ± 13 and 19 ± 13 nmol/liter), estradiol (83 ± 5 and 81 ± 21 pmol/liter), and dehydroepiandrosterone sulfate (3.6 ± 2.2 and 2.8 ± 1.7 nmol/liter). We conclude that in normogonadal nondiabetic males, the variability in plasma bioavailable testosterone concentrations is predictive of the variability in fat deposition in the sc adipose tissue compartments of both truncal and peripheral areas. Low plasma levels of bioavailable testosterone do not independently predict excessive insulin resistance, ß-cell dysfunction, or hepatic glucose output in normogonadal men.

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