Is There a Link between Low Testosterone and Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus?

New research finds that patients with type 2 diabetics mellitus and low testosterone levels are 6 times more likely than those with normal testosterone levels to have increased carotid artery intima media thickness (CIMT) and decreased endothelial function.

“Extensive evidence from observational studies has indicated a strong association between low serum T and the presence of metabolic syndrome and increased cardiovascular risk factors,” wrote the authors of the study, which appears in the Journal of Clinical Endocrinology & Metabolism.

However, they continued, “this is the first cross-sectional study evaluating the association between major atherosclerotic disease markers and low serum testosterone levels in middle-aged men with type 2 diabetes.”

Researchers examined 115 middle-aged men who had type 2 diabetes mellitus (T2DM) but no cardiovascular disease. Blood tests found that 79 of the men had normal total plasma testosterone levels (>12.1 nmol/L, or >3.5 ng/mL) while 36 of them fell below that threshold.

The researchers then used ultrasound to assess CIMT and atherosclerotic plaque, another blood test to measure C-reactive protein (CRP) and brachial-artery flow-mediated dilation to measure endothelial function.

Patients with low levels of testosterone were more likely than those with normal levels to have CIMT of 0.1 cm or greater (80% vs. 39%, odds ratio [OR] 6.41; 95% confidence interval [CI] 2.5—16.4, P < .0001).

They were also more likely to have atherosclerotic plaques (68.5% vs. 44.8%, OR 2.60, 95% CI 1.12—6.03, P < .0001), and endothelial dysfunction (80.5% vs. 42.3%, OR 5.77, 95% CI 2.77–14.77, P < .003).

What’s more, men with low testosterone levels tended to have higher CRP levels (2.74 mg/L ± 5.82 mg/L vs. 0.89 mg/L ± 0.88 mg/L, P < .0001).

The researchers then used multiple logistic regression analyses to adjust for age, diabetes mellitus duration, HbA1c, lipids, treatment effect, and body mass index.

They found, after controlling for all those factors, that low total testosterone levels were independently associated with greater CIMT (OR 8.43, 95% CI 2.5—25.8) and endothelial dysfunction (OR 5.21, 95% CI 1.73–15.66) but not with the presence of atherosclerotic plaques (OR 1.77, 95% CI 0.66–4.74).

The potential consequences associated with low testosterone levels seemed even higher when all 3 factors were considered together to calculate the risk of vascular disease for each patient. Some 54% of the patients with low testosterone but only 10% of the patients with normal testosterone levels faced significantly elevated danger.

The study authors noted several limitations to their work and particularly stressed both the lack of information about whether patients smoked and the lack of longitudinal follow-up needed to track the progression of risk factors into actual cardiac disease.

The authors also noted that their study provides no direct evidence that supplementing testosterone in diabetic men with low levels of the hormone might reduce their risk of heart disease. They did, however, urge others to test the idea.

“It is not clear whether low testosterone has a direct role in atherogenesis or is merely a marker of more advanced atherosclerotic disease,” they wrote.

“Prospective randomized studies are needed to assess the clinical significance of our findings and the clinical impact of testosterone replacement on cardiovascular risk factors in diabetic patients with low total testosterone.”