EFFECTS OF VARIOUS LIPID-LOWERING TREATMENTS IN DIABETICS

The frequency of all forms of atherosclerotic vascular disease is much greater in diabetics than in nondiabetics. Abnormalities in both the quantity and the quality of lipoproteins are among the many factors that can contribute to this. The most frequent quantitative lipoprotein abnormality in diabetics is hypertriglyceridemia. High-density lipoprotein (HDL) levels may be reduced, normal, or increased depending on the type of diabetes, its treatment, and the presence or absence of obesity. Low-density lipoprotein (LDL) levels in diabetics generally are not different from those in nondiabetics. The qualitative changes in lipoprotein composition may include alterations in the C apolipoproteins that could retard very low-density lipoproteins (VLDL) catabolism, enrichment of LDL and HDL with triglyceride, and modifications of LDL (e.g., glycosylation or oxidation) that makes it more atherogenic. The present rationale for the treatment of LDL abnormalities in diabetics is based on extrapolation from intervention trials in nondiabetics. These trials have suggested targets for plasma and LDL cholesterol levels. To date, no similar trials have been conducted in diabetics. Hence, it is not known whether the same or even lower LDL targets should apply to diabetics. Primary intervention trials have also shown the benefits, at least in nondiabetics, of increasing HDL levels. There is increasing evidence to support a cardiovascular risk effect of hypertriglyceridemia and one secondary intervention trial has demonstrated benefit associated with the correction of this. An added benefit of triglyceride reduction, at least in the milder diabetics, appears to be an improvement in insulin sensitivity. Fibrates are the drugs of choice for the correction of hypertriglyceridemia. In addition to reducing plasma levels of triglyceride, some fibrates may increase HDL. Occasionally, a combination of different lipid-lowering drugs may be needed. This may be the case if a single drug by itself does not produce the desired reduction. It may also be the case if, in using one lipid-lowering drug, another lipid abnormality develops. In general, the side effects of the lipid-lowering drugs in the otherwise healthy diabetic are no different than those seen in the nondiabetic. However, the presence of renal, hepatic, or gastrointestinal complications of diabetes may necessitate special attention to the patient's potential to develop side effects.