Acute hyperinsulinemia and very-low-density and low-density lipoprotein subfractions in obese subjects

Background: The influence of hyperinsulinemia on concentrations of lipoprot ein subfractions in obese, nondiabetic persons has not been clarified. Objective: We analyzed VLDL and LDL subfractions before and after a euglyce mic, hyperinsulinemic clamp. Design: Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obese patients, obese patien ts with type 2 diabetes, and nonobese control subjects. Results: Hyperinsulinemia tended to reduce concentrations (x(over bar): 20% ) of large, triacylglycerol-rich VLDL, in obese patients but had a minor ef fect on VLDL, and VLDL,. Placing obese patients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insu lin sensitivity on VLDL. VLDL, concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (x(over bar): 62%; P < 0.01). VLDL, concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL, concentrations decreased in both groups, in contrast with the change s seen in the insulin-sensitive patients and control subjects. Acute hyperi nsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes. Conclusions: Insulin resistance appears to be the primary determinant of th e modifications to VLDL subfraction concentrations. Our results suggest a c ontinuum of impaired insulin action on VLDL, ranging from that in healthy p ersons to that in patients with type 2 diabetes, in which obese patients oc cupy a transition state. Insulin resistance may also play a role in detrime ntal modifications to the LDL profile by allowing the development of hypert riglyceridemia.