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

Abstract

Background: The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified. Objective: We analyzed VLDL and LDL subfractions before and after a euglycemic, 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 patients with type 2 diabetes, and nonobese control subjects. Results: Hyperinsulinemia tended to reduce concentrations (x̄: 20%) of large, triacylglycerol-rich VLDL1 in obese patients but had a minor effect on VLDL2 and VLDL3. Placing obese patients into insulin- sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL1 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 (x̄: 62%; P < 0.01). VLDL1 concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL3 concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia 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 the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obese patients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia.