Insulin resistance is independently associated with postprandial alterations of triglyceride-rich lipoproteins in type 2 diabetes mellitus.

Abstract

To evaluate the role of insulin resistance in development of postprandial dyslipidemia in type 2 diabetic patients in an experimental setting in which these patients were compared with nondiabetic subjects at similar glucose and insulin blood levels. Eight type 2 diabetic patients in optimal blood glucose control and 7 control subjects (aged 50.0+/-2.6 and 48.1+/-1.3 years; body mass index 28.3+/-1.2 and 25.6+/-1.1 kg/m2; fasting plasma triglycerides 1.12+/-0.13 and 0.87+/-0.08 mmol/L, respectively; mean+/-SEM; NS) consumed a mixed meal during an 8-hour hyperinsulinemic glycemic clamp. Mean blood glucose during clamp was approximately 7.8 mmol/L, and plasma insulin during the preprandial steady state was approximately 480 pmol/L in both groups, that differed for insulin sensitivity (M/I value lower in diabetic subjects [1.65+/-0.30 and 3.42+/-0.60; P<0.05]). Subjects with diabetes had higher postprandial levels of lipids and apolipoprotein B (apoB) in large very low-density lipoprotein (incremental area for triglycerides 1814+/-421 versus 549+/-153 micromol/Lx6 hours; P<0.05; cholesterol 694+/-167 versus 226+/-41 micromol/Lx6 hours; P<0.05; apoB-48 6.3+/-1.0 versus 2.6+/-0.7 mg/Lx6 hours; P<0.05; apoB-100 56.5+/-14.9 versus 26.2+/-11.0 mg/Lx6 hours; NS). Basal lipoprotein lipase (LPL) activity before and after meal was higher in diabetic subjects, whereas postheparin LPL activity 6 hours after the meal was similar. Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.