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

Michiaki      Fukui; Yoshihiro      Kitagawa; Hiroyuki      Ose; Goji      Hasegawa; Toshikazu      Yoshikawa; Naoto      Nakamura

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.

Keywords: Testosterone, Dehydroepiandrosterone, Insulin resistance, Atherosclerosis, Type 2 diabetes, Men