Association of proinsulin-like molecules with lipids and fibrinogen in non-diabetic subjects--evidence against a modulating role for insulin.

Abstract

Elevated concentrations of proinsulin-like molecules, other than insulin, may be associated with abnormalities of cardiovascular risk factors, promoting atherogenesis and thrombosis. Using specific assays we examined the relationship of levels of insulin, intact proinsulin and des-31,32 proinsulin to blood pressure, lipids, fibrinogen, factor VII and albumin excretion rate in 270 europids with normal glucose tolerance. After correcting for age and body mass index, fasting and 2-h insulin concentrations were significantly associated with those of total and LDL-cholesterol (r = 0.18-0.22), HDL-cholesterol (both r = -0.20) and triglycerides (r = 0.21 and 0.18), but not with blood pressure. Concentrations of intact and des-31,32 proinsulin showed significant associations with those of total and LDL-cholesterol (r = 0.20-0.23), HDL-cholesterol (r = -0.31 and -0.32) and triglycerides (r = 0.22 and 0.26). Fasting insulin and intact proinsulin concentrations were significantly associated with fibrinogen (r = -0.15 and 0.18). Concentrations of proinsulin-like molecules comprised less than 10% of all insulin-like molecules, and so were calculated not to influence previously described relationships between insulin concentrations and cardiovascular risk factors measured using non-specific assays. In multiple regression analyses des-31,32 proinsulin concentration was more strongly associated with those of HDL-cholesterol (negatively), LDL-cholesterol and triglycerides than fasting insulin concentrations, while intact proinsulin replaced insulin concentrations in their relationships with fibrinogen. Our results show correlations between dyslipidaemia and proinsulin-like molecules at concentrations at which biological, insulin-like, activity appears unlikely. We also show relationships between LDL-cholesterol and fibrinogen and the proinsulin-like molecules.(ABSTRACT TRUNCATED AT 250 WORDS)