Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

Aims/hypothesis Proinsulin is increased in persons at cardiovascular risk. Increased secretion of proinsulin relative to insulin has been suggested as a sign of defective conversion of proinsulin to insulin and C-peptide and is associated with beta cell dysfunction. It has also been suggested that proinsulin has more of a pro-atherogenic effect than insulin, the levels of which are also increased in the insulin resistance state. In this prospective population-based study, we examined whether the proinsulin:insulin ratio (PIR) or insulin:glucose ratio (IGR, an insulin resistance surrogate) predicted carotid plaque size in nondiabetic participants. Materials and methods The study included 1,859 men and 1,998 women aged 25-82 years from the Tromsø Study, who were examined with B-mode high resolution ultrasound at baseline in 1994-1995 and at follow-up in 2001-2002. All images were computer processed to yield mm² measures of plaque. Proinsulin and insulin were measured at baseline. All analyses were stratified for sex. Results After adjusting for age, baseline plaque area, BMI, cholesterol, HDL-cholesterol, HbA₁c, IGR, albumin:creatinine ratio, fibrinogen, BP and lifestyle factors (tobacco smoking, alcohol consumption, physical activity), PIR was significantly associated with plaque size at follow-up in women but not men. For each SD in the PIR in women, the mean plaque area increased by 0.97 mm² (95% CI 0.44-1.50). IGR was not associated with carotid plaque size. Conclusions/interpretation The PIR is associated with progressive carotid artery plaque size in women.