Study Shows Testosterone is Insulin Sensitizer and Metabolic Hormone

“This is the first definitive evidence that testosterone is an insulin sensitizer and hence a metabolic hormone,” says Dandona, senior author on the paper and SUNY Distinguished Professor and chief of the Division of Endocrinology, Diabetes and Metabolism.

The study is the first randomized, double-blind, placebo-controlled study of testosterone treatment in Type 2 diabetic men that has comprehensively investigated the role of insulin resistance and inflammation, before and after treatment with testosterone.

The University at Buffalo researchers found that low testosterone levels were associated with significantly decreased insulin sensitivity. This was demonstrated by a 36 percent decrease in the rate at which glucose is taken up by tissues when patients with low testosterone were infused with insulin to maintain a set concentration of insulin.

The study included 94 men with Type 2 diabetes. Prior to being treated, the 44 men in the study with low testosterone levels expressed significantly lower levels of insulin signaling genes in adipose tissue reflected in diminished insulin sensitivity. These men were randomized to receive a testosterone injection or a placebo every week for 24 weeks.

“We saw a dramatic increase in insulin sensitivity, demonstrated by a 32 percent increase in the uptake of glucose by tissues in response to insulin,” says Dandona.  

At the same time, there was a similar increase in the expression of the major genes that mediate insulin signaling.

While there was no change in body weight, testosterone treatment produced a reduction in total body fat of 3 kilograms while increasing muscle mass by the same amount.

While patients’ hemoglobin A1C (HbA1c) levels did not go down, a necessary indicator that testosterone can help control diabetes, Dandona notes that fasting glucose levels had diminished significantly. These patients were already well controlled, so changes in HbA1c were difficult to change in the short term.

He says that a significant improvement in HbA1c may eventually be seen when longer term studies are carried out.

“Testosterone treatment for men, where indicated, will also improve sexual function and increase skeletal muscle strength and bone density,” explains Dandona.

“Our previous work has shown that obesity is associated with oxidative stress and inflammation, and inflammatory mediators are known to interfere with insulin signaling,” says Dandona.

He and his co-authors have been reporting on the relationship between insulin sensitivity and testosterone in Type 2 diabetic males since the publication of a 2004 paper that demonstrated the association between low testosterone levels and Type 2 diabetes.

They extended this association to obesity in 2010 with a study of more than 2,000 obese men, and they found that 33 percent of Type 2 diabetics — whether or not they were obese — and 25 percent of non-diabetic obese males, have low testosterone concentrations.

Dandona is also interested in how testosterone treatment may impact insulin resistance and inflammation in specific patient populations, such as those with chronic renal failure and hypogonadism. 

He was senior author on a 2015 paper published in the European Journal of Endocrinology reporting that two-thirds of Type 2 diabetic men with chronic kidney disease have low testosterone levels and that among patients on dialysis, 80 percent have low testosterone. 

Additionally, the UB researchers study how obesity in young men affects testosterone levels, a topic they published on in 2012, when they found that obese teens have 50 percent less testosterone than their lean peers.

“Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes,” funded by the National Institutes of Health, was published in Diabetes Care.

Faculty co-authors in the Department of Medicine include:

• Husam Ghanim, PhD, research associate professor
• Manav Batra, MBBS, assistant professor
• Nitesh D. Kuhadiya, MD, MPH, clinical assistant professor
• Antoine Makdissi, MD, associate professor
• Ajay Chaudhuri, MD, associate professor

Sandeep Dhindsa, MD, and Sartaj Sandhu, MD, are other co-authors along with Sanaa Abuaysheh, Kelly Green and Jeanne Hejna.

Mark Punyanitya, of Image Reading Center, Inc., is also a co-author.