Role of Endogenous Androgen Against Insulin Resistance and Athero-sclerosis in Men with Type 2 Diabetes

Abstract

Age-related decline in serum testosterone and dehydroepiandrosterone sulfate concentrations occur in men. Low concentrations of these endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. Moreover, men with diabetes have significantly less circulating androgen than nondiabetic men. Here, we summarize how androgen affects insulin resistance and atherosclerosis in men with type 2 diabetes. Low serum concentrations of endogenous androgens are associated with visceral fat accumulation. Androgen deprivation by castration to treat prostate cancer increases insulin resistance, while testosterone administration in type 2 diabetic men with androgen deficiency improves glucose homeostasis and decreases visceral fat, in addition to alleviating symptoms of androgen deficiency including erectile dysfunction. Androgen correlates inversely with severity of atherosclerosis and has beneficial effects upon vascular reactivity, inflammatory cytokine, adhesion molecules, insulin resistance, serum lipids, and hemostatic factors. Because men with type 2 diabetes have relative hypogonadism, testosterone supplementation could decrease both insulin resistance and atherosclerosis.

The relationship between hepatic steatosis and skeletal muscle mass index in men with type 2 diabetes

“…Other possible explanation is serum concentrations of testosterone and estrogen. Low serum testosterone concentrations are associated with insulin resistance [43], decreased muscle mass [44] and hepatic steatosis [45]. Taking these finding together, it seems plausible that the SMI is associated with hepatic steatosis.…”

Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis

“…Thus, blood DHEA-S level has been found independently and inversely associated with immunosenescence, autoimmune diseases, non-alcoholic steatohepatitis, insulin resistance, atherosclerosis and systemic arterial hypertension [8][9][10][11]27]. Evidence indicates that low levels of DHEA-S predict death from all causes, cardiovascular disease and ischaemic heart disease in older males [28].…”

“…insulin resistance, atherosclerosis, systemic arterial hypertension and Sjögren syndrome [9][10][11]. Accordingly, DHEA has been proposed as an ageing-protective molecule.…”

Relationship between insulin and hypogonadism in men with metabolic syndrome

“…On the other hand, there is evidence that a low testosterone level in men would result in insulin resistance and abdominal obesity, as well as be a predictive factor for the development of type 2 diabetes mellitus (6,(45)(46)(47)(48)(49). It has been proposed that the hypogonadism resultant from prostate cancer treatment, by the blockage of gonadotrophins by GnRH-agonists (50,51) or by castration (52), could be associated with an increase in insulin levels.…”