Plasma cholesteryl ester transfer protein (CETP) activity has been reported
to decline during a hyperinsulinemic-euglycemic clamp. It has been suggest
ed that this suppressive effect of acute hyperinsulinemia is linked to whol
e body insulin sensitivity, and that the insulin resistance that accompanie
s obesity leads to high plasma CETP activity found in obese subjects. In th
e present study, we used 2 experimental approaches to examine the putative
link between CETP and insulin action. First, we examined if the clamp-induc
ed suppression of plasma CETP activity is linked to whole body insulin sens
itivity. 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 w
ithout weight loss. CETP activity decreased in response to the clamp proced
ure 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 s
ensitivity had no statistical effect on the clamp-induced suppression of pl
asma 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 acid diabetes were negated. Plasma CETP ac
tivity was measured in 41 women (12 insulin-sensitive lean; 8 insulin-resis
tant lean; 10 insulin-sensitive obese; 11 insulin-resistant obese). The lev
el 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 ar
e linked to insulin and insulin sensitivity. These data suggest that the el
evated CETP activity found in obese patients is less associated with hyperi
nsulinemia and the accompanying insulin resistance, but rather is more rela
ted to some other metabolic complication of obesity. Copyright (C) 2001 by
W.B. Saunders Company.