Hypogonadism in men with obesity or type 2 diabetes

Description

Obesity and type 2 diabetes are important causes of hypogonadism. At least one third of men with type 2 diabetes have low free testosterone.1 LH and FSH were NOT elevated but lower, which means these men have hypogonadotropic hypogonadism. There was a significant inverse correlation of BMI with free testosterone.1

In a primary care clinic population comprising 1,451 nondiabetic and 398 diabetic men, free testosterone was measured by equilibrium dialysis.2 The prevalence of low free testosterone in lean, overweight, and obese nondiabetic men was 26%, 29% and 40%, respectively, and 44%, 44% and 50%, respectively, in diabetic men. The mean free testosterone concentration of diabetic men was significantly lower than that of nondiabetic men.2

Low free testosterone is also associated with an increased number of metabolic syndrome components.3 There is a large overlap between low testosterone, insulin resistance and features of the metabolic syndrome.

Even younger men with type 2 diabetes (18-35 years old) have significantly lower plasma concentrations of total and free testosterone and inappropriately low LH and FSH concentrations with a very high prevalence of hypogonadotrophic hypogonadism, when compared with type 1 diabetic patients of a comparable age. The potential implications for their sexual and reproductive function during prime reproductive years are profound.4

What is the mechanism underlying the association between insulin resistance and low testosterone? The hypothesis that elevated levels of estradiol would underlie this association has been refuted, and we now know that obese men with type 2 diabetes do not have elevated estradiol levels. The cause may be within the central nervous system. An experimental study published in Science showed that insulin resistance signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction.5

Prof. Dandona presents results conducted by his group, showing that testosterone treatment for 6 months in hypogonadal men reduced insulin resistance and subcutaneous fat mass (approx. 3 kg) and increased lean mass (approx. 3 kg), without changing body weight. At baseline, the expression of insulin signaling genes (IR-beta, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower and was upregulated after testosterone treatment. Insulin sensitivity was significantly improved in the testosterone group, as indicated by a 32% increase in glucose infusion rate during the HE clamp, and insulin resistance (as indicated by HOMA-IR) was reduced accordingly.6


 

Speakers

Prof. Dr. med. Marija Pfeifer

Paresh Dandona, M.D., PhD
SUNY Distinguished Professor of Medicine
Head, Division of Endocrinology Diabetes and Metabolism
State University of New York at Buffalo

References

  • Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 2004;89(11):5462-5468. Return to content
  • Dhindsa S, Miller MG, McWhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33(6):1186-1192. Return to content
  • Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A, Balercia G, Chiarini V, Forti G, Maggi M. Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol. 2006 Sep;50(3):595-604. Return to content
  • Chandel A, Dhindsa S, Topiwala S, Chaudhuri A, Dandona P. Testosterone concentration in young patients with diabetes. Diabetes Care. 2008 Oct;31(10):2013-7. Return to content
  • Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Müller-Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000 Sep 22;289(5487):2122-5. Return to content
  • Dhindsa S, Ghanim H, Batra M, et al. Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes. Diabetes Care. 2016;39(1):82-91. Return to content