Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients

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-kcal/kg IBW diet daily with GH (n = 9; rhGH, 0.15 IU/kg body weight/week) or placebo (n = 9) for 12 weeks. SUBJECTS: Eighteen newly-diagnosed obese type 2 diabetic patients (age 42-56y, body mass index 28.1 ± 2.7 kg/m²). 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 profiles; 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 significantly greater (0.98 ± 0.39 vs 0.52 ± 0.32 kg/kg, 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 significantly increased in only the GH-treated group (4.67 ± 1.05 vs 6.95 ± 0.91 mg/kg/min, P < 0.05). The GH-induced increase in GDR was positively correlated with the decrease in the ratio of visceral fat area/muscle area (r = 0.588, P = 0.001). Serum glucose levels and insulin- and FFA-area under the curve during OGTT and HbA_1c were significantly 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.