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 mm(2) 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, HbA(1c), 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 mm(2) (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.