Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes.
OBJECTIVE
Liver fat is increased in type 2 diabetes. We determined whether it is associated with impaired insulin clearance and to what extent insulin resistance, impaired insulin clearance, or secretion contribute to fasting hyperinsulinemia. We also examined whether insulin suppression of serum free fatty acid (FFA) correlates with liver fat.


METHODS
We compared 68 type 2 diabetic patients and age-, gender-, and body mass index (BMI)-matched nondiabetic subjects. Liver fat was determined by (1)H-MRS, body composition by magnetic resonance imaging, and insulin clearance and action on hepatic glucose production (HGP), glucose uptake, and serum FFA by the euglycemic insulin clamp technique (insulin 0.3 mU/kg x min) combined with infusion of [3-(3)H]glucose.


RESULTS
Liver fat was 54% higher and insulin clearance 24% lower in type 2 diabetic patients than nondiabetic subjects. The percent suppression of both HGP and serum FFA by insulin were comparable, but serum insulin concentrations were significantly higher (34 mU/L [interquartile range, 30-39 mU/L] vs 25 mU/L [interquartile range, 22-30 mU/L]; P < .0001) in the type 2 diabetic than the nondiabetic subjects. When this difference was taken into account, both hepatic and adipose tissue insulin sensitivity were impaired in the type 2 diabetic subjects. Liver fat correlated with insulin clearance (r = -0.41; P = .001), and hepatic (r = 0.46; P = .0001) and adipose tissue (r = 0.55; P < .0001) insulin sensitivity. Hepatic but not peripheral insulin sensitivity was independently associated with liver fat content. Insulin clearance and secretion were independent determinants of fasting serum insulin.


CONCLUSIONS
We conclude that increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance characterize type 2 diabetic patients.
Kotronen
Anna
A
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland. anna.kotronen@helsinki.fi
Juurinen
Leena
L
Tiikkainen
Mirja
M
Vehkavaara
Satu
S
Yki-Järvinen
Hannele
H
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011522:Protons; D012044:Regression Analysis
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011522:Protons