Postprandial amplification of lipoprotein abnormalities in controlled type II diabetic subjects: Relationship to postprandial lipemia and C-peptide/glucagon levels

Abstract

Lipoprotein abnormalities, mainly high very-low-density lipoprotein (VLDL) and low high-density lipoprotein (HDL) levels, increase the risk of coronary heart disease (CHD) in type II diabetic patients. To investigate the relationship between these lipoprotein abnormalities and the postprandial (PP) lipid-clearing capacity, triglyceride (TG) and hormonal levels were determined hourly up to the 4th hour after a mixed meal containing 32.5 g lipids/m 2 body surface in 14 treated non-obese type II diabetic patients with adequate nutritional and glycemic control (hemoglobin A 1C [HbA 1C] < 7%) and in 12 healthy subjects fasting TG moderately increased in diabetics (140 ± 70 v 66 ± 34 mg/dL, P < .01). Whereas fasting TG levels in patients showed a continuous distribution from 55 to 250 mg/dL, postprandial TG clearly identified two different subgroups. A “high-responder” or hypertriglyceridemic subgroup (HTG) showed PP TG levels significantly higher than control levels (290 ± 62 v 106 ± 41 mg/dL, P < .001), with higher fasting TG as well (181 ± 52, P < .01), whereas both fasting and PP TG levels were not different from control levels in the normotriglyceridemic (NTG) diabetic subgroup. The magnitude of the PP triglyceridemic area showed a negative correlation with HDL 2 cholesterol ( r = .66, P < .001) and a positive correlation with PP HDL 2 TG enrichment ( r = .80, P < .001). A negative correlation was evidenced between the glucagon/C-peptide molar ratio and total or incremental TG areas ( r = −.62, P < .01 and r = −.74, P < .001, respectively). No additional correlations were found in diabetic patients between any of these variables and glycemic control. Only HTG patients showed increased total and incremental PP TG areas when compared with controls, as well as associated abnormalities in lipoprotein levels and composition. They showed higher VLDL, intermediate-density lipoprotein (IDL), and apolipoprotein (apo) B levels, together with decreased HDL 2. In the postprandial state, they presented higher chylomicron levels and significant TG enrichment within HDL 2. Amplification of lipoprotein changes already present at fasting also occurred, mainly a significant increase in VLDL levels together with a decrease in the HDL 2 cholesteryl ester (CE) TG ratio, which suggests increased net lipid transfer between these lipoproteins. These findings indicate that non-obese treated diabetic patients with only moderate fasting hypertriglyceridemia present potentially atherogenic quantitative and qualitative lipoprotein abnormalities that are better evidenced in the PP state and may contribute to their higher CHD risk.