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.

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Abstract. We retrospectively investigated the effects of adding glimepiride in patients with type 2 diabetes showing suboptimal control by insulin therapy. Of 63 patients with poorly controlled insulin-treated type 2 diabetes (baseline HbA1c, 8.4 ± 0.6%), 32 were treated with insulin alone and 31 were given glimepiride in addition to insulin. HbA1c values, daily insulin dose, body weight, blood pressure, plasma lipid concentrations, and the number of hypoglycemic events were recorded at weeks 0, 12, 24, 36, 48, 60, and 72. HbA1c decreased by 1.1%, from 8.5 ± 0.6% to 7.4 ± 0.8% (P<0.0001) in patients treated with insulin plus glimepiride at 12 weeks, and improved glycemic control continued throughout the study. Required insulin dose was reduced significantly in patients treated with insulin plus glimepiride (from 29.4 ± 14.5 to 22.3 ± 12.1 units/day, P = 0.0187). Body weight increased significantly in patients treated with insulin plus glimepiride (from 57.0 ± 8.7 to 59.5 ± 9.2 kg, P = 0.0232). Adding glimepiride showed little effect on blood pressure, plasma total cholesterol, triglyceride, or HDL-cholesterol. Serum C peptide concentrations increased significantly in patients treated with insulin plus glimepiride (from 1.01 ± 0.71 to 1.28 ± 0.65 ng/ml, P = 0.0367). The number of hypoglycemic events did not differ between groups. Adding glimepiride to insulin therapy resulted in sustained improvement of glycemic control in patients with poorly controlled type 2 diabetes.