Effect of Type 1 Diabetes on the Gender Difference in Coronary Artery Calcification: a Role for Insulin Resistance?

Abstract

The objective of this is study was to examine whether estimated insulin resistance and insulin resistancerelated factors are associated with coronary artery calcification (CAC) in 1,420 asymptomatic participants in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. A total of 656 patients with type 1 diabetes and 764 control subjects aged 20 -55 years were examined. CAC was assessed by electron-beam computed tomography. Insulin resistance was computed with linear regression based on an equation previously validated in clamp studies on type 1 diabetic adults. Insulin resistance was associated with CAC (OR 1.6 in type 1 diabetes and 1.4 in control subjects, P < 0.001), independent of coronary artery disease risk factors. There was a male excess of CAC in control subjects (OR 2.7, adjusted for age, smoking, and LDL and HDL cholesterol levels) and in type 1 diabetic patients (OR 2.2, adjusted for the same factors and diabetes duration). After adjusting for insulin resistance, the CAC male excess in diabetic patients decreased from OR 2.2 (P < 0.001) to 1.8 (P ‫؍‬ 0.04). After adjustment for waist-tohip ratio, waist circumference, or visceral fat, the gender difference in CAC was not significant in diabetic subjects. In conclusion, gender differences in insulin resistance-associated fat distribution may explain why type 1 diabetes increases coronary calcification in women relatively more than in men.

The apolipoprotein A-IV Gln360His polymorphism predicts progression of coronary artery calcification in patients with type 1 diabetes

“…The CACTI study is a prospective cohort study of 1,416 subjects (652 with type 1 diabetes and 764 non-diabetic control subjects) that was designed to assess risk factors associated with the development and progression of subclinical CAD, measured by the presence of CAC, with the aim of identifying targets for the prevention of CAD [3,5,7] (Electronic supplementary material [ESM] Fig. 1).…”

“…The total CAC score was presented as a mean value of measurements from two independent CT scans performed within 5 min of each other during each visit [5,33]. Among the participants of the CACTI study, APOA4 genotyping data were available for 1,373 subjects (96.7% of the study population), 634 with type 1 diabetes and 739 from the control group, and 1,141 of whom completed the follow-up visit and were evaluated for CAC progression (ESM Fig.…”

“…While chronic hyperglycaemia [3,4] and insulin resistance [5,6] partially explain this excess CAD, little is known about the potential genetic determinants of accelerated coronary atherosclerosis in type 1 diabetes [7][8][9][10].…”

“…Rapid progression of CAC, observed on serial scanning, also predicts future coronary events [11]. It has been shown that diabetic patients have a significantly higher frequency of coronary calcification compared with individuals of the same age in the general population [5,13]. Coronary calcification has been shown to independently predict myocardial infarction (MI) or obstructive CAD in type 1 and type 2 diabetic patients [14][15][16].…”

“…The aim of our present study was to evaluate the association of the APOA4 polymorphisms with CAC progression in type 1 diabetic subjects and non-diabetic control subjects participating in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [5].…”