Plasma cholesteryl ester transfer protein activity is not linked to insulin sensitivity

Plasma cholesteryl ester transfer protein (CETP) activity has been reported to decline during a hyperinsulinemic-euglycemic clamp. It has been suggested that this suppressive effect of acute hyperinsulinemia is linked to whole body insulin sensitivity, and that the insulin resistance that accompanies obesity leads to high plasma CETP activity found in obese subjects. In the present study, we used 2 experimental approaches to examine the putative link between CETP and insulin action. First, we examined if the clamp-induced suppression of plasma CETP activity is linked to whole body insulin sensitivity. Plasma CETP activity was measured at the beginning and end of a 2-hour hyperinsulinemic-euglycemic clamp in 18 nondiabetic individuals before and after an exercise training regimen that improved insulin sensitivity without weight loss. CETP activity decreased in response to the clamp procedure in 16 of 18 subjects, and on average, by 9% (P <.001). While training decreased plasma CETP activity (10%, P <.05), the improvement in insulin sensitivity had no statistical effect on the clamp-induced suppression of plasma CETP activity (training*clamp, P =.26). Second, we examined if insulin resistance is associated with an elevation in fasting plasma CETP activity when the influence of adiposity and diabetes were negated. Plasma CETP activity was measured in 41 women (12 insulin-sensitive lean; 8 insulin-resistant lean; 10 insulin-sensitive obese; 11 insulin-resistant obese). The level of insulin sensitivity had no significant effect on fasting plasma CETP activity, but CETP levels were 25% higher in obese subjects (P <.01). Thus, neither experimental approach provided evidence that plasma CETP levels are linked to insulin and insulin sensitivity. These data suggest that the elevated CETP activity found in obese patients is less associated with hyperinsulinemia and the accompanying insulin resistance, but rather is more related to some other metabolic complication of obesity.