Testosterone Raises Insulin Sensitivity

SAN FRANCISCO -- Giving testosterone to men with type 2 diabetes who are deficient in the hormone improved their insulin sensitivity, researchers reported here.

In a randomized, controlled trial, type 2 diabetic men with hypogonadotropic hypogonadism had a significant 25% increase in insulin sensitivity after taking testosterone injections for 6 months, compared with no significant changes for men in the placebo group (P=0.01), Paresh Dandona, MD, PhD, of the University of Buffalo, and colleagues reported at the Endocrine Society meeting here.

"The conclusion from all of this is that hypogonadism in type 2 diabetes ... leads to an insulin-resistant state and a pro-inflammatory state, and that pro-inflammatory state may be contributing to insulin resistance by interfering with insulin signaling," Dandona said during a press briefing.

But, he added, taking testosterone for 6 months "reverses almost altogether the insulin-resistant state and exerts anti-inflammatory effects, consistent with the reversal of the mechanisms that lead to insulin resistance."

Studies have shown that about a third of all men with type 2 diabetes have hypogonadotropic hypogonadism, and researchers have questioned whether these patients will have worse insulin resistance.

To assess insulin resistance in this population -- as well as the effects of treatment with injectable testosterone -- Dandona and colleagues conducted a randomized controlled trial of 81 men with type 2 diabetes.

At baseline, those with hypogonadism had a higher body mass index (BMI) and a higher fat mass than those who didn't have low testosterone.

Dandona and colleagues found that hypogonadal men with type 2 diabetes had significantly lower insulin sensitivity than those who did not have hypogonadism (P=0.001), and that association remained even when controlling for weight and age (P=0.017), they reported.

Men were randomized to treatment with testosterone or placebo for 6 months.

The researchers found that after treatment, testosterone levels rose significantly for those in the treated group (256 ng/dL to 562 ng/dL, P=0.001) while there were no significant changes in the placebo group.

They also found that free testosterone rose dramatically (4.1 nmol/L to 12.4 nmol/L, P<0.001), while placebo patients had no significant changes in this parameter.

Dandona said there was a "dramatic" 25% increase in insulin sensitivity as measured by euglycemic clamp after these men took testosterone for 6 months (P=0.01), but there was no significant change in insulin sensitivity for the placebo group.

There were no changes in weight or in waist-to-hip ratio for either group, but total lean body mass increased significantly for testosterone patients (P=0.004). At the same time, fat mass significantly diminished in this group (P=0.02).

"The short of this message is, 2 kg (4.5 lbs.) of fat were replaced by 2 kg (4.5 lbs.) of lean body mass," Dandona said.

The researchers also found, as expected, that mean insulin concentrations fell with the sensitization to insulin in the drug-treated group (11.6 to 7.1, P<0.05), and HOMA-IR also fell significantly for these patients (3.5 to 2.8, P<0.05).

Lipid concentrations didn't change in either group, but there was significant improvement in sexual desire among those on testosterone (P=0.05), Dandona said.

He noted that concentrations of free fatty acids also fell dramatically for men on testosterone therapy.

"It's important to realize that free fatty acids are ... associated with oxidative stress, inflammation, and abnormal vascular reactivity," Dandona told MedPage Today. "When levels are high, as they are in insulin-resistant patients, reducing them on their own is extremely worthwhile."

Dandona noted that his group's study is ongoing and that they will next assess fat and muscle biopsies to determine further metabolic effects of testosterone.

The study was supported by the National Institutes of Health.

Modificado por última vez en Lunes, 29 Julio 2013 19:41

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