CETP, a key player in atherogenic dyslipidemia of Type II diabetes

The WHO has predicted that a worldwide epidemic of Type II diabetes, affecting some 300 million persons, can be envisaged in 2003. The key features of the atherogenic lipid phenotype characteristic of Type II diabetes are low HDL-cholesterol levels, mild to marked hypertriglyceridemia involving VLDL and VLDL remnants, and elevated concentrations of both small dense LDL, and free fatty acids (FFA) in the fasting state; indeed, FFA are implicated in the development of peripheral insulin resistance. Elevated transfer rates of cholesteryl esters (CE) from HDL to atherogenic apoB100 lipoproteins (VLDL, IDL, LDL) mediated by cholesteryl ester transfer protein (CETP) underlie the low HDL-C levels typical of Type II diabetes, identifying CETP as a prime pharmacological target. The future clinical application of CETP inhibitors in Type II diabetic subjects, in association with agents which would act synergistically by reducing concentrations of atherogenic CE acceptor lipoproteins (e.g., statins, fibrates, cholesterol absorption inhibitors), is therefore especially attractive. [Copyright &y& Elsevier]