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 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. CONCLUSIONS: Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.

Exogenous and endogenous postprandial lipid abnormalities in type 2 diabetic patients with optimal blood glucose control and optimal fasting triglyceride levels.

The aim of this study was to evaluate exogenous and endogenous lipoprotein responses to a standard fat-rich meal in type 2 diabetic patients with optimal fasting triglyceridemia and optimal blood glucose control. Seven type 2 diabetic patients and five nondiabetic controls (age, 49 +/- 7 and 48 +/- 4 yr; body mass index, 28.3 +/- 3.6 and 25.1 +/- 3.6 kg/m(2); mean +/- SD) were given, after at least 12 h of fasting, a standard fat-rich meal. Before and over the 6 h after the meal, serial blood samples were taken for determination of glucose, insulin, lipids, lipoproteins, apolipoprotein B-48 (apo B-48), apo B-100, free fatty acids, and lipoprotein lipase activity. The main abnormality in the postprandial lipid response of diabetic patients involved large very low density lipoproteins. In these particles, apo B-48, apo B-100, cholesterol, and triglyceride incremental areas were, in fact, significantly higher in diabetics compared with controls [7.08 +/- 2.65 vs. 1.17 +/- 0.88 mg/liter.h, 65.5 +/- 11.5 vs. 12.4 +/- 1.77 mg/liter.h, 29.7 +/- 3.9 vs. 13.1 +/- 3.1 mg/dl.h (0.77 +/- 0.10 vs. 0.34 +/- 0.08 mmol/liter.h), 170 +/- 31 vs. 94 +/- 22 mg/dl.h (1.93 +/- 0.35 vs. 1.06 +/- 0.25 mmol/liter.h)] (all P < 0.05; mean +/- SEM). Postprandial preheparin lipoprotein lipase plasma activity was, if anything, higher in diabetic patients. In conclusion, even with fasting normotriglyceridemia and optimal blood glucose control, type 2 diabetic patients are characterized, in the postprandial period, by a significant increase in large very low density lipoproteins of both endogenous and exogenous origins.