Trattamento dell’ipercolesterolemia nel soggetto con diabete mellito: Aggiornamento sugli approcci terapeutici

The term dyslipidemias covers a range of quantitative and/or qualitative lipoprotein abnormalities. These may be primary or secondary. Diabetic dyslipidemia is a type of secondary dyslipidemia, with an important role in cardiovascular disease in type 2 diabetes subjects. In these patients, insulin resistance is responsible for overproduction and secretion of the highly atherogenic very-low-density lipoprotein (VLDL). Insulin resistance also promotes the production of small, dense low-density-lipoprotein (LDL) and reduces high-density lipoprotein (HDL) production. Cardiovascular disease remains a leading cause of morbidity and mortality in diabetic patients. The small dense LDL particles appear to play a pivotal role in the etiology of atherosclerosis and the correction of LDL-cholesterol reduces the risk of cardiovascular death. The European guidelines for the management of dyslipidemias therefore recommend a LDL-cholesterol goal < 100 mg/dl in diabetic subjects without cardiovascular events. If triglycerides (TG) are elevated (> 400 mg/dl) they recommend a Non-HDL cholesterol goal < 130 mg/dl for primary prevention. Statins are the first line of LDL-lowering therapy in diabetic patients. Combined therapy with ezetimibe and statin could be useful in patients at very high cardiovascular risk. The effect of a fibrate as an add-on treatment to a statin may improve the lipid profile in diabetic individuals with high TG and low HDL cholesterol. As regards new therapies, recent data from phase III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably reduce LDL cholesterol. These might therefore be useful in diabetic patients with concomitant diseases such as familial dyslipidemia, recurrent cardiovascular events, elevated LDL cholesterol after addition of a second drug to the maximal statin dose, or statin intolerance.