EFFECT OF EXOGENOUS HYPERINSULINEMIA ON ATHEROGENESIS IN CHOLESTEROL-FED RABBITS

To examine the hypothesis that hyperinsulinaemia promotes atherosclero sis, cholesterol-fed rabbits were injected subcutaneously with 6 IU of human insulin (n = 16) or placebo (n = 20) daily for 24 weeks; inject ion of insulin resulted in hyperinsulinaemia for up to 16 h after inje ction. Compared to placebo rabbits, insulin-treated rabbits had higher levels of insulin antibodies in plasma, similar levels of intermediat e density low density and high density lipoprotein cholesterol and sim ilar activities of hepatic and lipoprotein lipase in post-heparin plas ma, but lower levels of plasma C-peptide, blood glucose, postprandial plasma triglycerides, plasma cholesterol and very low density lipoprot ein cholesterol, On univariate analysis,,with and without adjustment f or differences in plasma cholesterol levels between the two groups, th ere were no significant differences in extent or severity of atheroscl erosis between insulin and placebo rabbits. Furthermore, after combini ng the results from all the rabbits to examine plasma insulin levels a nd the other variables mentioned above as predictors of atherosclerosi s severity, plasma insulin level was not a predictor, on univariate or multiple linear regression analysis; the first ranked independent pre dictors were postprandial intermediate density lipoprotein cholesterol in the arch, and postprandial plasma triglyceride in both the thoraci c and abdominal aorta. These results suggest that exogenous hyperinsul inaemia does not promote atherogenesis in cholesterol-fed rabbits, but that postprandial levels of intermediate density lipoprotein choleste rol or plasma triglycerides may be involved in atherogenesis.