The 6th Annual World Congress on the Insulin Resistance Syndrome

This is the second of a series of articles based on presentations at the 6th Annual World Congress on the Insulin Resistance Syndrome held 25–27 September 2008 in Los Angeles, California.

Gary Lewis (Toronto, Canada) discussed the effect of prolonged free fatty acid (FFA) elevation on pancreatic β-cell function. FFAs are essential for maintenance of basal insulin secretion, and acute FFA elevation increases glucose-stimulated insulin secretion, but prolonged FFA elevation consistently impairs glucose-stimulated insulin secretion (GSIS) in vitro. There is no consensus regarding in vivo effects in part because of FFA-induced insulin resistance, so that lack of change in insulin levels may actually indicate failure of compensatory increase in insulin secretion. Lewis described studies of this with graded glucose infusion. After doubling FFA levels with heparin plus lipid infusion, comparing acute with prolonged FFA elevation, insulin secretion did not change, but there was reduction in insulin sensitivity (1). Given the hyperbolic relationship between insulin sensitivity and insulin secretion, the product of the two, termed the disposition index, is a more important measure (2). With use of this measure, GSIS increases by ∼50% with the acute increase in FFA levels, countering FFA-induced reduction in insulin sensitivity, so that the disposition index is unchanged, whereas with prolonged FFA elevation, β-cell compensation is not shown—a phenomenon particularly observed in obese nondiabetic subjects (3,4). Elevated glucose has additive effects to FFA in reducing GSIS in obese subjects (5). Monounsaturated (MUFA), polyunsaturated (PUFA), and saturated (SFA) fats appear to differentially affect GSIS. Longer FFA chain length and degree of saturation are associated with greater insulin resistance. In a study comparing olive (78% MUFA), safflower (78% PUFA), and palm (50% SFA) oils, ingested over 24 h, insulin sensitivity was particularly decreased by SFA, leading to a greater reduction in the disposition index (6), although …