HYPERINSULINEMIA AND INSULIN-RESISTANCE ARE ASSOCIATED WITH MULTIPLE ABNORMALITIES OF LIPOPROTEIN SUBCLASSES IN GLUCOSE-TOLERANT RELATIVES OF NIDDM PATIENTS

We studied the subclasses of plasma lipoproteins in normolipidemic, gl ucose-tolerant male relatives of noninsulin dependent diabetic patient s (NIDDM), who represented either the lowest (n = 14) or the highest ( n = 18) quintiles of fasting plasma insulin. The higher plasma triglyc eride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoprot eins. The concentrations of larger VLDL(1), smaller VLDL(2) particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respe ctively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL(1), VLD L(2), and IDL particles enriched in lipids and poor in protein. The lo wer plasma HDL cholesterol level in the high insulin group (1.20 mmol/ l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a c onsequence of a 27% reduction of HDL(2a) concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL(3a), HDL(3b), and HDL(3c) subclasses. On the other hand, the percentages of triglyc erides in HDL(2b), HDL(2a), HDL(3a), and HDL(3b) subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (Pt 0.01 or less). In the combined group, th e concentration of VLDL(1) and VLDL(2), correlated positively with the concentrations of LDL(2) and LDL(3) and negatively with HDL(2b) and H DL(2a) subclasses (P < 0.05 or less). In conclusion, normolipidemic, g lucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. The se abnormalities are not observed in insulin-sensitive relatives, sugg esting that they develop in concert with insulin resistance.