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Atherosclerosis and Lipoproteins |
From the Department of Clinical and Experimental Medicine (G.A., C.D.N., C.I., L.P., L.D.M., S.C., G.R., A.A.R.), Federico II University, Naples, and the Department of Endocrinology and Metabolism (S.D.P.), University of Pisa, Italy.
Correspondence to Giovanni Annuzzi, MD, Department of Clinical and Experimental Medicine, Federico II University, Via Pansini 5, 80131 Napoli, Italy. E-mail annuzzi{at}unina.it
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/Lx6 hours; P<0.05; cholesterol 694±167 versus 226±41 µmol/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.
Conclusions Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.
In an experimental setting, taking care of the effects of hyperglycemia and hyperinsulinemia (hyperinsulinemic glycemic clamp,) insulin-resistant type 2 diabetic patients showed higher postprandial levels of lipids and apoB in large VLDL compared with controls, indicating that insulin resistance is a proper target to correct postprandial dyslipidemia in type 2 diabetes.
Key Words: postprandial lipemia large VLDL insulin resistance type 2 diabetes lipoprotein lipase
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