Plasma Fatty Acids, Adiposity, and Variance of Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus

Author:

Kelley David E.12,Williams Katherine V.1,Price Julie C.3,McKolanis Therese M.1,Goodpaster Bret H.1,Thaete F. Lee3

Affiliation:

1. Departments of Medicine (D.E.K., K.V.W., T.M.M., B.H.G.), Pittsburgh, Pennsylvania 15261

2. Medical Research Service, Pittsburgh Veterans Affairs Medical Center (D.E.K.), Pittsburgh, Pennsylvania 15240

3. Radiology (J.C.P., F.L.T.), University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Abstract

Skeletal muscle insulin resistance (IR) is typically severe in type 2 diabetes mellitus (DM). However, the factors that account for interindividual differences in the severity of IR are not well understood. The current study was undertaken to examine the respective roles of plasma FFA, regional adiposity, and other metabolic factors as determinants of the severity of skeletal muscle IR in type 2 DM. Twenty-three subjects (12 women and 11 men) with type 2 DM underwent positron emission tomography imaging using[ 18F]2-fluoro-2-deoxyglucose during euglycemic insulin infusions (120 mU/min·m2) to measure skeletal muscle IR, using Patlak analysis of the tissue activity curves. Body composition analysis included body mass index, fat mass, and fat-free mass by dual energy x-ray tomography, and computed tomography determinations of visceral adiposity, thigh adipose tissue distribution, and muscle composition. Body mass index, fat mass, subfascial adiposity in the thigh, and visceral adipose tissue (VAT) were all significantly related to skeletal muscle IR (r = −0.48 to −0.63; P< 0.01). However, the strongest simple correlate of IR in skeletal muscle was insulin-suppressed plasma FFA (r = −0.81; P < 0.001). VAT was the sole component of adiposity that significantly correlated with insulin-suppressed plasma FFA concentration (r = 0.64; P < 0.001). These findings indicate that the severity of skeletal muscle IR in type 2 DM is closely related to the IR of suppressing lipolysis and that plasma fatty acids and VAT are key elements mediating the link between obesity and skeletal muscle IR in type 2 DM.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference43 articles.

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4. Interaction between glucose and free fatty acid metabolism in human skeletal muscle.;Kelley;J Clin Invest,1993

5. Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM subjects.;Piatti;Diabetologia,1996

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