Testosterone restores insulin sensitivity in patients with diabetes and hypogonadism
LAS VEGAS — Testosterone supplementation has an insulin sensitizing effect in patients with diabetes and hypogonadotropic hypogonadism, including increases in expression of mediators of signaling and reductions in factors that interfere, according to research presented at the AACE 23rd Annual Scientific and Clinical Congress.
“Our data for the first time shows men with type 2 diabetes and hypogonadotropic hypogonadism are more insulin resistant as compared to men who have normal testosterone,” Manav Batra, MD, of the University of Buffalo, said during a presentation. “This hypogonadotropic hypogonadism is associated with lower expression of mediators of insulin signaling in adipose tissue as compared to men who have normal testosterone. Following the testosterone replacement in these men, the expression of mediators of insulin signaling increases, and there is a reduction in expression of mediators interfering with insulin signaling that improves insulin sensitivity.”
In a randomized trial, Batra and colleagues recruited 91 men with hypogonadotropic hypogonadism (HH, n=41) and type 2 diabetes to evaluate the effect of testosterone replacement on insulin resistance.
Patients with HH were assigned testosterone (250 mg) or placebo (1 ml saline) injected intramuscularly every 2 weeks for 6 months. The researchers collected fasting blood samples, and performed fat biopsies and hyperinsulinemic euglycemic clamps, at baseline and at 6 months.
Results from the clamps showed that patients with HH have 28% lower glucose infusion rates (GIR) for a given rate of insulin infusion vs. eugonadal patients; a 30% increase in GIR was observed with testosterone treatment, consistent with a reversal of insulin resistance.
In HH adipose tissue compared to eugonadal, basal expression of mediators of insulin signaling — including insulin resistance (IR), insulin receptor substrate (IRS-1) and glucose transporter (GLUT-4) — was lower by 32%, 35% and 27% (P<0.05), respectively.
Following testosterone, the adipose tissue expression of IR, IRS-1 and GLUT-4 increased significantly by 63±15%, 54±17% and 59±14%, respectively, and a decrease was observed in the expression of protein-tyrosine phosphatase by 23±8% and toll-like receptor 4 by 21±11%, which interfere with insulin signaling.
Reductions were seen in several others areas that interfere with signaling, including mononuclear cells expression of suppressor of cytokine signaling-3 by 27±8% and plasma concentrations of free fatty acids and C-reactive protein by 35% and 26%, (P<0.05) respectively.
For more information: Batra M. Abstract 303. Presented at: AACE 23rd Annual Scientific & Clinical Congress; May 13-18, 2014; Las Vegas, Nevada.
Disclosures: Endocrine Today could not confirm disclosures at the time of press.