Very low density lipoprotein metabolism in diabetes mellitus

Abstract

The concentration of VLDL and their major lipid, triglyceride, are regulated at many levels from the initial availability of the substrates needed for their synthesis all the way to the function of the enzymes and receptors involved in their removal from plasma. It should be clear from this review that in diabetes mellitus metabolic derangements resulting from the absolute lack of insulin or from resistance to the actions of insulin can affect VLDL triglyceride metabolism at any or all of these regulatory points. The outcome of this interplay between diabetes and VLDL metabolism is the common occurrence of elevated plasma VLDL and triglyceride concentrations in individuals with both Type 1 and Type 2 diabetes mellitus. Mildly elevated plasma levels of triglycerides are nearly universal in diabetics; more significant hypertriglyceridemia can be the consequence of either metabolic decompensation or the concomitant inheritance of a familial pattern of hyperlipoproteinemia. The combination of the latter two situations usually presents with as severe hypertriglyceridemia. Although deregulation can occur at many points, the most common abnormality associated with hypertriglyceridemia in human diabetes appears to be overproduction of VLDL triglycerides. Increased rates of synthesis of VLDL apoB may also be a common consequence of diabetes. The basis for this belief is the accumulated data from kinetic studies in humans and in experimental models of diabetes in rats. Although the latter may also demonstrate defects in catabolism when insulin deficiency is severe, catabolic abnormalities appear to be uncommon as the primary force in the development of hypertriglyceridemia in humans. Finally, despite the complexity of the systems regulating VLDL metabolism and the many metabolic abnormalities that may be present in diabetic subjects, it appears that reduction of the hyperglycemia by means of dietary or pharmacologic interventions is associated with normalization of the rates of synthesis and catabolism of the VLDL and their triglycerides. In view of the probable atherogenecity of VLDL, particularly in individuals with diabetes, such intervention must be aimed at both plasma glucose and lipid concentrations.