Insulin Resistance Is Independently Associated With Postprandial Alterations of Triglyceride-Rich Lipoproteins in Type 2 Diabetes Mellitus

Objective— 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. Methods and Results— 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 ≈7.8 mmol/L, and plasma insulin during the preprandial steady state was ≈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 μmol/L×6 hours; P <0.05; cholesterol 694±167 versus 226±41 μmol/L×6 hours; P <0.05; apoB-48 6.3±1.0 versus 2.6±0.7 mg/L×6 hours; P <0.05; apoB-100 56.5±14.9 versus 26.2±11.0 mg/L×6 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. Conclusions— Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.