DIABETIC DYSLIPIDEMIA

In patients with insulin resistant or type II diabetes, changes in the composition of lipoproteins occur in the absence of large changes in the absolute levels of cholesterol and triglycerides. A small increase in serum cholesterol reflects both a reduction in high density lipopr otein (HDL) cholesterol and an increase in very low density lipoprotei n (VLDL) cholesterol. There are also increases in the triglyceride con tent of HDL and low density lipoprotein (LDL). Overproduction of VLDL occurs partly due to the resistance to insulin and also because of low er lipoprotein lipase activity. Furthermore, the lipoprotein phenotype in patients with type II diabetes is similar to that in familial comb ined dyslipidaemia. This is associated with an increased residence tim e for triglyceride rich particles and exposure to cholesterol ester tr ansfer protein (CETP) which facilitates the transfer of cholesterol to VLDL and chylomicrons in exchange for triglyceride. CETP can also hav e an atherogenic effect by reducing the cholesterol in HDL. These fact ors combine to increase the degree of cholesterol enrichment in remnan t particles and thereby exacerbate the atherosclerotic process. The hi gh levels of circulating LDL, which result from the overproduction of VLDL and impaired lipoprotein lipase activity, are glycated in the pre sence of elevated blood glucose. These glycated particles are primaril y removed by a non-receptor mediated pathway that results in the forma tion of foam cells. These changes in lipoprotein profile markedly incr ease the risk of coronary events and treatment that can reduce triglyc erides and VLDL cholesterol and increase HDL cholesterol has clear ben efits.