Authors Farias JM, Tinetti M, Khoury M, Umpierrez GE.
Review Date October 2014
Citation Journal of Clinical Endocrinology and Metabolism [epub ahead of print] dx.doi.org/10.1210/jc.2014-2585
Type 2 diabetes (T2D) is associated with higher risk of cardiovascular disease, and cardiovascular events are the main cause of death. Low total testosterone (T) is associated with an increased risk of atherosclerotic complications. However, the magnitude of this association in middle-aged patients with T2D has not been determined. It has been estimated that up to one third of patients with T2D have low serum T concentrations and clinical evidence of hypogonadism. The cause and effect relationship of hypogonadism on risk markers of atherosclerotic and vascular disease is not known.
To assess atherosclerotic disease markers in T2D patients with normal and low plasma total testosterone.
A total of 115 male patients, aged younger than 70 years, without a history of cardiovascular events, were recruited from 148 men attending a single centre in Argentina. Men were divided into 2 groups: normal [≥ 12.1 nmol/L, n = 79] and low [< 12.1 nmol/L, n = 36] total T. All had the following markers assessed: carotid artery carotid intima-media thickness (IMT) and atherosclerotic plaque were measured with high-resolution B-mode ultrasound; endothelial function was assessed by brachial artery flow-mediated dilation. Plasma glucose and lipids, total T level and highly sensitive C-reactive protein (Hs-CRP) were also measured.
Mean age of the study group was 56.6 years and mean duration of T2D was 6 years. Low serum T levels were found in 31% of patients (n=36). Carotid IMT was negatively correlated with total T concentration (r = -0.39, p < 0.0001). Compared with subjects with normal T, a higher proportion of patients with low total T had carotid IMT of 0.1 cm or greater [80% vs 39%, odds ratio (OR) 6.41; 95% CI 2.5 to 16.4, P < 0.0001], atherosclerotic plaques (68.5% vs 44.8%, OR 2.60, 95% CI 1.12 to 6.03, P < 0.0001); endothelial dysfunction (80.5% vs 42.3%, OR 5.77, 95% CI 2.77 to 14.77, P < 0.003), and higher Hs-CRP levels (2.74 +/- 5.82 vs 0.89 +/- 0.88 mg/L, P < 0.0001). Similar results were found for free T.
Multiple logistic regression analyses adjusted for age, diabetes mellitus duration, hemoglobin A1c, lipids, treatment effect, and body mass index reported that a low total T level was independently associated with IMT of 0.1 cm or greater [OR 8.43 (95% CI 2.5–25.8)] and endothelial dysfunction [OR 5.21 (95% CI 1.73 to 15.66)] but not with the presence of atherosclerotic plaques (OR 1.77, 95% CI 0.66 to 4.74).
Low T is associated with more advanced atherosclerotic disease markers in middle- aged patients with T2D. However, it is not clear that T replacement in older men with diabetes will reduce the risk of cardiovascular events. Randomised trials are needed to assess the effect of testosterone replacement in middle-aged men with diabetes and hypogonadism.
Points to Note
- By demonstrating cross-sectional associations of T with atherosclerotic disease markers, this study adds to previous findings of an association between low testosterone and a higher risk of cardiovascular disease in men with diabetes.
- Nearly one third of the patients with diabetes were found to have low testosterone.
- The association of T with increased endothelial dysfunction and carotid artery intima-media thickness was independent of age, BMI, diabetes duration, lipid levels, and treatment of hypertension.
- The study limitations included a cross-sectional design such that progression of atherosclerosis could not be determined and some cardiovascular risk factors, such as smoking, were not measured.
- The effect of T replacement on cardiovascular risk factors in men with diabetes and hypogonadism needs to be assessed in clinical trials.