Dissimilar association of conventional immuno-reactive versus specific insulin with cardiovascular risk factors: A consequence of proinsulinaemia?

In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean blood pressure (MBP) and pulse pressure. In a multiple regression analysis, adjusted for age, sex and obesity, a 1.3-fold stronger inverse association with HDL-C levels was found for IRI than for ISI, with a 1.6-fold better fit of the regression equation. The positive association of insulin with TG was 1.6- fold stronger for IRI compared to ISI, with a 2.5-fold better fit. In contrast, the positive association of IRI with the various blood pressure parameters was 1.5-1.9-fold weaker than for ISI, with a 2.1-3.8-fold worse fit. Both PI:ISI ratio and PI were independently associated with TG levels, but not with HDL-C. The PI:ISI ratio, but not PI, was associated with blood pressure, but dependent on glycaemia. In conclusion, compared to ISI, IRI overestimates the association of insulin with serum lipids and underestimates the association of insulin with blood pressure. The use of non-specific insulin assays may explain the inconsistencies in the findings of previous epidemiological studies.