Testosterone with diet and exercise reverses metabolic syndrome and improves glycemic control in hypogonadal men with newly diagnosed type 2 diabetes
Fifty-two week treatment with diet and exercise plus transdermal testosterone reverses the Metabolic Syndrome (MetS) and improves glycemic control in men with newly diagnosed Type 2 Diabetes and subnormal plasma testosterone. AE Heufelder, F Saad, M Bunck, and L Gooren. November/December 2009. Journal of Andrology;30:(6);726-733.
In a single blind 52-week randomized clinical trial, 32 hypogonadal men (morning plasma testosterone concentration lower than 12 nmol/L, reference range >14 nmo/l) with recently diagnosed Type 2 Diabetes (T2D) and with Metabolic Syndrome (MetS) underwent supervised diet and exercise (D&E). Half of this group received D&E with testosterone administered as a relatively low dose (50 mg) gel (Testogel®) once daily. No glucose-lowering agents were administered prior to or during the study period.1
What is known
Men with T2D have lower serum testosterone concentrations than men without diabetes and there is an inverse association between testosterone levels and HbA1c concentrations.2,3
In men with low plasma testosterone, the risk of T2D appears to be greater4 and a meta-analysis shows that testosterone levels are significantly lower in men with T2D.5
In hypogonadal men, the effect of testosterone supplementation on glycemic control has been mixed. Two studies found no effect,6,7 whereas Kapoor et al (2006)8 found that testosterone therapy improved glycemic control.
Individuals with T2D often have disturbances consistent with the Metabolic Syndrome,9 and individuals with the MetS have increased risk of developing T2D.10
Treatment with exogenous testosterone in those with low testosterone levels has been shown to improve metabolic features of MetS8 and produce beneficial effects on circulating high-sensitive C-reactive protein (hsCRP) levels in individuals with T2D. Some consider low testosterone to be a significant contributor in the development of insulin resistance and MetS in some men.9
Few clinical studies have evaluated the effect of normalization of serum testosterone concentrations on glucose homeostasis6,7 and results from such studies have showed limited beneficial effects of testosterone administration.8
What this study adds
In this study, insulin sensitivity, measured by HOMA, improved in two groups of men receiving supervised D&E. This effect was significantly greater when testosterone was added.1
Testosterone treatment also significantly improved circulating levels of adiponectin and hsCRP, key serum markers respectively of insulin sensitivity and hepatic steatosis.1
The changes in both adiponectin and hsCRP were significantly correlated with the therapy induced changes in bio-available testosterone.1 These findings are not in line with a previous placebo controlled, randomized study in hypogonadal T2D patients. In these studies, adiponectin levels decreased after 3 to 6 months of treatment with intramuscular mixed testosterone esters.11 (These opposing findings in the circulating adiopnectin concentrations could be a result of the different routes of testosterone administration used with widely variable testosterone levels.)
This study found a decline in serum levels of hsCRP upon D&E plus testosterone, a finding not reported by Kapoor et al (2007)12,but replicated in a study by Haider et al (2009)13.