Relationship between Hyperinsulinemia and Remnant Lipoprotein Concentrations in Patients with Impaired Glucose Tolerance

Abstract

This study was performed to explore further the association between insulin resistance and plasma remnant lipoprotein (RLP) concentration. For this purpose we used the sum of the plasma insulin concentrations before and 30, 60, 90, 120, and 180 min after a 75-g oral glucose load (ΣIRI) as a surrogate measure of insulin resistance in 61 subjects with impaired glucose tolerance. ΣIRI was determined on 2 occasions, before and 16 weeks after initiation of a diet and exercise program. At baseline, ΣIRI correlated with the sum of the plasma glucose concentrations in response to the 75-g oral glucose load (r = 0.26; P < 0.04) as well as plasma concentrations of triglyceride (r = 0.21; P = 0.09), RLP-cholesterol (r = 0.41; P < 0.001), and RLP-triglyceride (r = 0.46; P < 0.001). In contrast, neither total (r = 0.07) nor high density lipoprotein (HDL) cholesterol (r = 0.04) concentrations correlated withΣ IRI. ΣIRI was lower in 42 subjects following life-style intervention, associated with significant (P < 0.005) reductions in Σglucose, and fasting glucose, insulin, triglyceride, RLP-cholesterol, and RLP-triglyceride concentrations. However, none of these variables decreased in the 19 subjects whoseΣ IRI did not fall. Finally, the change in ΣIRI following intervention with diet and exercise was significantly associated with differences in Σglucose (r = 0.63; P < 0.001) and fasting glucose (r = 0.26; P < 0.05), insulin (r = 0.79; P < 0.001), triglyceride (r = 0.29; P < 0.03), RLP-cholesterol (r= 0.71; P < 0.001), and RLP-triglyceride (r = 0.49; P < 0.001) concentrations. These results demonstrate that variations in concentrations of RLPs are highly correlated with changes in ΣIRI, consistent with the possibilities that 1) RLP measurements are useful estimates of insulin resistance; and 2) an increase in RLP concentrations may provide the mechanistic link between insulin resistance and coronary heart disease.