We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers, no insulin or lipid-lowering drug treatment) and 82 control subjects, IMT, plasma CET, CETP mass, and lipids were determined. HDL cholesterol was lower, whereas IMT, pulse pressure, plasma triglycerides, and plasma CET and CETP concentration were higher in diabetic patients versus control subjects. In diabetic patients, plasma CET was positively determined by triglycerides (P < 0.001), non-HDL cholesterol (P < 0.001), CETP (P ‫؍‬ 0.002), and the interaction between CETP and triglycerides (P ‫؍‬ 0.004). In control subjects, plasma CET was positively related to triglycerides (P < 0.001) and non-HDL cholesterol (P < 0.001). HDL cholesterol was inversely related to plasma CET in each group (P < 0.01 for both). IMT was positively associated with plasma CET in diabetic (P ‫؍‬ 0.05) and control (P < 0.05) subjects after adjustment for age, sex, and pulse pressure. No independent relationship with plasma CETP mass was found. Plasma CET is a positive determinant of IMT. Plasma CETP mass, in turn, is a determinant of CET with an increasing effect at higher triglycerides. These data, therefore, provide a rationale to evaluate the effects of CETP inhibitor treatment on plasma CET and on cardiovascular risk in diabetes-associated hypertriglyceridemia. Diabetes 54:3554 -3559, 2005 T he inverse relationship between HDL cholesterol and cardiovascular disease is well documented in nondiabetic and type 2 diabetic populations (1,2). Among other mechanisms, the cholesteryl ester transfer protein (CETP)-mediated process of plasma CET plays a key role in HDL metabolism. CETP transfers cholesteryl esters from HDL toward lipoproteins of lowerdensity classes in exchange for triglycerides (3-5). Hence, the plasma CET process is likely to contribute to low HDL cholesterol, as frequently observed in type 2 diabetes (5).Only few studies have addressed the effect of plasma CETP levels and the rate of plasma CET on cardiovascular risk in humans. A small study showed a positive correlation between the plasma CETP concentration and carotid artery intima-media thickness (IMT) (6). In addition, plasma CETP mass was shown to be a positive determinant of incident coronary artery disease but only in subjects with high triglycerides (7). The CET process itself could, however, also represent a beneficial pathway by enabling the transport of HDL-derived cholesteryl esters back to the liver via VLDL and LDL (3). The impact of the plasma CET process on atherosclerosis development remains, therefore, uncertain (8).CETP inhibitors represent a new class of drugs that effectively raise HDL cholesterol (9,10). While pharmacological inhibition of circulating CETP has been shown to retard atherosclerosis in animal experiments (11), the effect of this treatment on ca...

Plasma LCAT activity is elevated in MetS and may be a marker of subclinical atherosclerosis. Our findings do not support the contention that strategies to elevate LCAT are necessarily beneficial for cardioprotection.

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