HYPERINSULINEMIA AND ABDOMINAL OBESITY AFFECT THE EXPRESSION OF HYPERTRIGLYCERIDEMIA IN HETEROZYGOUS FAMILIAL LIPOPROTEIN-LIPASE DEFICIENCY

We have reported three missense mutations (G188E, P207L, and D250N) in the lipoprotein lipase (LPL) gene among French-Canadians, resulting i n the absence of measurable postheparin plasma LPL activity in homozyg otes. Presence of triglyceride-and cholesterol-rich VLDL, as well as c holesterol-poor HDL particles, has been shown in heterozygotes affecte d by partial reduction in postheparin LPL activity. However, significa nt heterogeneity in their plasma triglyceride levels has been found, e ven among individuals carrying the same LPL gene mutation, indicating that factors other than LPL deficiency could affect the phenotypic exp ression of hypertriglyceridemia in the heterozygous state. The aim of the present study was to examine the combined effects of abdominal fat accumulation and hyperinsulinemia on plasma triglyceride levels among heterozygous patients for familial LPL deficiency. Based on sex and B MI, 43 heterozygotes (25 women and 18 men) were matched with noncarrie r control subjects. Our data indicate that heterozygotes with higher a bdominal fat deposition, as defined as waist girth values above the 50 th percentile, had higher plasma triglyceride levels than nonobese het erozygotes. However, an important proportion of male heterozygote subj ects were hypertriglyceridemic, even in absence of abdominal obesity, suggesting that another factor(s) was involved in the modulation of hy pertriglyceridemia in these subjects. Indeed, multivariate analyses re vealed that fasting hyperinsulinemia was a significant correlate of hy pertriglyceridemia among these heterozygotes. Results of the present s tudy indicate that abdominal obesity and hyperinsulinemia both have de leterious effects on plasma triglyceride levels in familial LPL defici ency. It is suggested that heterozygotes with moderate obesity and/or insulin resistance may be at higher risk of coronary artery disease be cause of the expression of an atherogenic lipoprotein phenotype among these patients.