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/m2) 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-(3)H]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.
Juurinen
Leena
L
Department of Medicine, Helsinki University of Technology, Finland.
Tiikkainen
Mirja
M
Häkkinen
Anna-Maija
AM
Hakkarainen
Antti
A
Yki-Järvinen
Hannele
H
D000410:Alanine Transaminase / Q000097:blood; D001481:Basal Metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000737:chemistry* / Q000378:metabolism*; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010084:Oxidation-Reduction
D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D008687:Metformin; D000410:Alanine Transaminase; D005947:Glucose