LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.
Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.
Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.
Dr. Manav Batra
Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.
The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.
"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.
"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.
The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.
"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.
"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.
In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.
Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.
Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.
Dr. Batra disclosed no relevant conflicts of interest.