Beneficial effects of a long-term oral l-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients

Because chronic l-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral l-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with l-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, l-arginine supplementation further decreased FM ( P < 0.05) and waist circumference ( P < 0.0001), preserving FFM ( P < 0.03), and improved mean daily glucose profiles ( P < 0.0001) and fructosamine ( P < 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P < 0.001), superoxide dismutase (index of antioxidant capacity; P < 0.01), and adiponectin levels ( P < 0.02) increased, whereas basal endothelin-1 levels ( P < 0.01) and leptin-to-adiponectin ratio ( P < 0.05) decreased in the l-arginine group. Long-term oral l-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.