Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes

We determined whether insulin therapy changes liver fat content ( LFAT) or hepatic insulin sensitivity in type 2 diabetes. Fourteen patients with type 2 diabetes ( age 51 +/- 2 yr, body mass index 33.1 +/- 1.4 kg/ m(2)) treated with metformin alone received additional basal insulin for 7 mo. Liver fat ( proton magnetic resonance spectroscopy), fat distribution ( MRI), fat- free and fat mass, and whole body and hepatic insulin sensitivity ( 6- h euglycemic hyperinsulinemic clamp combined with infusion of [ 3-H-3] glucose) were measured. The insulin dose averaged 75 +/- 10 IU/ day ( 0.69 +/- 0.08 IU/ kg, range 24 - 132 IU/ day). Glycosylated hemoglobin A1c ( Hb A1c) decreased from 8.9 +/- 0.3 to 7.4 +/- 0.2% ( P < 0.001). Whole body insulin sensitivity increased from 2.21 +/- 0.38 to 3.08 +/- 0.40 mg/ kg fat- free mass ( FFM) < min ( P < 0.05). This improvement could be attributed to enhanced suppression of hepatic glucose production ( HGP) by insulin ( HGP 1.04 +/- 0.28 vs. 0.21 +/- 0.19 mg/ kg FFM . min, P < 0.01). The percent suppression of HGP by insulin increased from 72 +/- 8 to 105 +/- 11% ( P < 0.01). LFAT decreased from 17 +/- 3 to 14 +/- 3% ( P < 0.05). The change in LFAT was significantly correlated with that in hepatic insulin sensitivity ( r = 0.56, P < 0.05). Body weight increased by 3.0 < 1.1 kg ( P < 0.05). Of this, 83% was due to an increase in fat- free mass ( P < 0.01). Fat distribution and serum adiponectin concentrations remained unchanged while serum free fatty acids decreased significantly. Conclusions: insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.