Postprandial lipoproteins and cardiovascular disease risk in diabetes mellitus

Abstract

Diabetes mellitus is associated with increased risk for atherosclerotic cardiovascular disease (CVD). Recent prospective studies in healthy individuals suggest that the postprandial triglyceride (TG) level is a better independent predictor for assessing future CVD events than fasting TG levels. In contrast, results have been more controversial among diabetic patients, as some studies report a positive association between postprandial TG and CVD. This raises the issue of to what extent postprandial TG levels may be of predictive value in the diabetic population. One possibility impacting on the predictive power of postprandial TG in identifying CVD risk may be the presence of other risk factors, including alterations in lipid and lipoprotein metabolism, which could make it more difficult to identify the impact of postprandial lipemia on cardiovascular risk. The findings provide a challenge to develop a better approach to assess the impact of postprandial lipemia on CVD risk under diabetic conditions.

Fig. 1

Postprandial lipoprotein metabolism in diabetes. Insulin resistance plays a central role in the development of diabetic dyslipidemia. Under normal physiologic conditions, insulin suppresses lipolysis from adipose tissue and hepatic very low density lipoprotein (VLDL) production. However, hyperinsulinemia in the postprandial state and insulin resistance in type 2 diabetes initiates a dyslipidemic triad of high triglyceride, low high-density lipoprotein (HDL) cholesterol and high small, dense low-density lipoprotein (LDL) levels. Prolonged residence of triglyceride-rich lipoproteins (TRLs) in the circulation promotes the transfer of HDL or LDL cholesteryl esters for triglyceride, mediated by cholesteryl ester transfer protein (CETP). LDL can undergo hydrolysis by hepatic lipase (HL) or lipoprotein lipase (LPL), which hydrolyzes triglycerides from the core of LDL, resulting in production of smaller, denser particles. Moreover, triglyceride-enriched HDL particles become smaller, denser (HDL 3b and 3c) and are more rapidly catabolized, contributing to low plasma HDL in insulin resistance and type 2 diabetes. apo apolipoprotein; CM chylomicron; FFA free fatty acid; RLP remnant lipoprotein