OBJECTIVE:To evaluate the effects of low-dose growth hormone (GH) therapy combined with diet restriction on changes in body composition and the consequent change in insulin resistance in newly-diagnosed obese type 2 diabetic patients. DESIGN: Double-blind and placebo-controlled trial of 25-kcalakg IBW diet daily with GH (n 9; rhGH, 0.15 IUakg body weightaweek) or placebo (n 9) for 12 weeks. SUBJECTS: Eighteen newly-diagnosed obese type 2 diabetic patients (age 42 ± 56 y, body mass index 28.1 AE 2.7 kgam 2 ). MEASUREMENTS: Body composition and fat distribution parameters (by bioelectrical impedance analyzer and CT scans), serum IGF-1; serum glucose, insulin and free fatty acid (FFA) during oral glucose tolerance test (OGTT); HbA 1c ; serum lipid pro®les; and glucose disposal rate (GDR) by euglycemic hyperinsulinemic clamp at baseline and after treatment. RESULTS: The fraction of body weight lost as fat lost was signi®cantly greater (0.98 AE 0.39 vs 0.52 AE 0.32 kgakg, P`0.05) and visceral fat area was decreased more in the GH-treated group compared to the placebo-treated group (27.9 vs 21.6%, P`0.05). Lean body mass and muscle area were reduced in the placebo-treated group, whereas an increase in both was observed in the GH-treated group. GDR the was signi®cantly increased in only the GH-treated group (4.67 AE 1.05 vs 6.95 AE 0.91 mgakgamin, P`0.05). The GH-induced increase in GDR was positively correlated with the decrease in the ratio of visceral fat areaamuscle area (r 0.588, P 0.001). Serum glucose levels and insulin-and FFA-area under the curve during OGTT and HbA 1c were signi®cantly decreased after GH treatment. LDL-cholesterol level was decreased in only the GH-treated group. CONCLUSION: Low-dose GH treatment combined with dietary restriction resulted not only in a decrease of visceral fat but also in an increase of muscle mass with a consequent improvement of the insulin resistance observed in obese type 2 diabetic patients.

The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.