The Dark Side of Testosterone Deficiency: II. Type 2 Diabetes and Insulin Resistance

Abstract

A considerable body of evidence exists suggesting a link among reduced testosterone plasma levels, type 2 diabetes (T2D), and insulin resistance (IR). Hypogonadal men are at higher risk for T2D. Here we evaluate the relationships between testosterone, metabolic syndrome (MetS), T2D, and IR and discuss the relationships among androgen deficiency and these factors, especially as it ultimately relates to the development of cardiovascular disease and erectile dysfunction (ED). Thus, a comprehensive literature search was carried out using PubMed, and relevant articles pertinent to androgen deficiency, T2D, IR, MetS, and ED were reviewed and discussed. Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Treatment of prostate cancer patients with surgical or medical castration exacerbates IR and glycemic control, strengthening the link between testosterone deficiency and onset of T2D and IR. Androgen therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and HbA1c levels. We suggest that androgen deficiency is associated with IR, T2D, MetS, and with increased deposition of visceral fat, which serves as an endocrine organ, producing inflammatory cytokines and thus promoting endothelial dysfunction and vascular disease.

The role of testosterone in type 2 diabetes and metabolic syndrome in men

“…In addition, several large prospective studies have shown that low testosterone levels predict development of type 2 diabetes in men. There is persuasive epidemiological evidence from several longitudinal population studies that low testosterone is an independent risk factor for the development of both the metabolic syndrome and type 2 diabetes in later life (2,5). The Massachusetts Male Aging Study (MMAS) and the Multiple Risk Factor Intervention Trial (MRFIT) have shown that low levels of total testosterone and SHBG (which is associated with insulin resistance) were both independent risk factors in middle-aged men who later developed diabetes.…”

Acute cardiac decompensation in a patient with beta‐thalassemia and diabetes mellitus following cessation of chelation therapy

“…There is a close association between insulin resistance (IR) and testosterone deficiency 27. Free and total testosterone levels are inversely correlated with indices of IR such as insulin levels and homeostatic model assessment of insulin resistance (HOMA‐IR) 28, 29, 30.…”

Testicular and thyroid function as survival predictors in the elderly patient candidate to surgery

“…The most recent studies have also identified that men with CVD show significantly lower serum levels of bioavailable T than those men with negative coronary angiography (see Box 1 for CV safety issues and T-replacement). Numerous studies have found a direct association between male obesity and lower plasma T levels [2], and there is also an independent association between plasma T concentration and insulin sensitivity; [3,4] obese men with diabetes appear to be at particularly high risk of developing secondary hypogonadism [5]. This cluster of abnormalities is associated with an increased risk of diabetes and CVD, affecting not only quality of life but also life expectancy and the impact of resilience on surgical recovery and wound-healing.…”