Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus

Skeletal muscle insulin resistance (IR) is typically severe in type 2 diabe tes mellitus (DM). However, the factors that account for interindividual di fferences in the severity of IR are not well understood. The current study was undertaken to examine the respective roles of plasma FFA, regional adip osity, and other metabolic factors as determinants of the severity of skele tal muscle ER in type 2 DM. Twenty-three subjects (12 women and 11 men) wit h type 2 DM underwent positron emission tomography imaging using [F-18]2-fl uoro-2-deoxyglucose during euglycemic insulin infusions (120 mU/min.m(2)) t o measure skeletal muscle IR, using Patlak analysis of the tissue activity curves. Body composition analysis included body mass index, fat mass, and f at-free mass by dual energy x-ray tomography, and computed tomography deter minations of visceral adiposity, thigh adipose tissue distribution, and mus cle composition. Body mass index, fat mass, subfascial adiposity in the thi gh, and visceral adipose tissue (VAT) were all significantly related to ske letal muscle IR (r = -0.48 to -0.63; P < 0.01). However, the strongest simp le 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 significa ntly correlated with insulin-suppressed plasma FFA concentration (r = 0.64; P < 0.001). These findings indicate that the severity of skeletal muscle I R in type 2 DM is closely related to the IR of suppressing lipolysis and th at plasma fatty acids and VAT are key elements mediating the link between o besity and skeletal muscle IR in type 2 DM.