Gastroenterology

Gastroenterology

Volume 135, Issue 1, July 2008, Pages 122-130
Gastroenterology

Clinical–Liver, Pancreas, and Biliary Tract
Increased Liver Fat, Impaired Insulin Clearance, and Hepatic and Adipose Tissue Insulin Resistance in Type 2 Diabetes

https://doi.org/10.1053/j.gastro.2008.03.021Get rights and content

Background & Aims: 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 1H-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 · min) combined with infusion of [3-3H]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.

Section snippets

Subjects

The nondiabetic subjects and the type 2 diabetic patients were recruited by newspaper advertisements and by contacting occupational health services in Helsinki based on the following inclusion criteria: (1) age 18–70 years; (2) no known acute or chronic disease, other than obesity, hypertension, or type 2 diabetes, based on history, physical examination, and standard laboratory tests; and (3) alcohol consumption <20 g/day. Exclusion criteria were evidence of any other disease, treatment with

Subject Characteristics (Table 1)

The nondiabetic subjects and type 2 diabetic patients were comparable with respect to age, gender, BMI, percent whole body fat, blood pressure, S-liver enzyme, and LDL cholesterol concentrations. Fasting plasma glucose, HbA1c, and fS-triglycerides were higher, and fS-HDL cholesterol lower in the type 2 diabetic patients than the nondiabetic subjects. Intraabdominal fat was 44%, and liver fat 54%, higher in the type 2 diabetic patients than in the nondiabetic subjects.

Serum Insulin Concentrations in the Basal State and During Insulin Infusion (Table 2)

FS-insulin concentrations

Discussion

In the present study, we cross-sectionally examined whether insulin clearance is impaired in type 2 diabetic patients, and how it relates to liver fat and hepatic, peripheral, and adipose tissue insulin sensitivity in a relatively large number of type 2 diabetic patients and age-, gender-, and BMI-matched nondiabetic subjects. Liver fat content was 54% higher and insulin clearance 24% lower in the type 2 diabetic patients than the nondiabetic subjects. The decrease in insulin clearance resulted

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    Supported by research grants from the Academy of Finland, the Sigrid Juselius Foundation, and Novo Nordisk Foundation. This work is part of the project “Hepatic and adipose tissue and functions in the metabolic syndrome” (www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (Contract LSHM-CT-2005-018734).

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