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Targets for Intervention in Dyslipidemia in Diabetes

From the Department of Diabetes and Endocrinology, Trinity College Dublin, Dublin, Ireland

Address correspondence and reprint requests to Professor Gerald H. Tomkin, Diabetes Research Foundation, Clontra, Quinns Rd., Shankill, Co Dublin, Ireland. E-mail: gerald.tomkin{at}tcd.ie

Treatment for dyslipidemia in diabetes reduces cardiovascular events. Diabetes is associated with major abnormalities in fatty acid metabolism. The resulting disturbance results in an abnormal lipoprotein cascade from the large chylomicron through to the small HDL particle. This suggests that drugs that alter formation of the chylomicron particle might have a very important role in diabetic dyslipidemia. Achieving normal glycemia will reverse the abnormalities in fatty acid metabolism, but this is difficult, particularly as the disease progresses. Genes that regulate cholesterol absorption and excretion have been described (Niemann Pick C1-like 1 [NPC1-L1] and ATP binding cassette proteins [ABC] G5 and G8). An effective NPC1-L1 inhibitor (ezetimibe) improves the reduction in cholesterol caused by statins. Agonists of ABCG5 and G8 may become important in the treatment of dyslipidemia. Microsomal triglyceride transfer protein (MTP) is responsible for the assembly of the chylomicron and VLDL particles. New MTP inhibitors, acting only on the intestine, are exciting possible treatments. The advisability of sitosterol-enriched foods to lower cholesterol may have to be reassessed for patients with diabetes, since these products may lead to an increase in chylomicron sitosterol in diabetic patients. More successful treatment of diabetic dyslipidemia is essential if we are to reduce the burden of cardiovascular disease so commonly found in diabetes.

Abbreviations: apo, apolipoprotein • CHD, coronary heart disease • MTP, microsomal triglyceride transfer protein • NEFA, nonesterified free fatty acid • PPAR, peroxisome proliferator–activated receptor

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