Glycaemic control modifies the haptoglobin 2 allele-conferred susceptibility to coronary artery disease in Type 1...

We aimed to assess whether the association of the haptoglobin 2 allele with coronary artery disease is modified by glycaemic control in a prospective cohort study of individuals with childhood-onset Type 1 diabetes.

Coronary artery disease events (death from coronary artery disease, confirmed myocardial infarction, stenosis ≥50%, revascularization) were assessed between 1986 and 2013 among 480 individuals with Type 1 diabetes (baseline age 28 years; diabetes duration 19 years). Better glycaemic control was defined as an updated mean HbA_1c during follow-up of <8% (64 mmol/mol).

In crude models, the incidence of coronary artery disease increased with the number of haptoglobin 2 alleles (hazard ratio 1.34, 95% CI 1.05-1.71). This association was more pronounced in those with better than in those with worse glycaemic control (P interaction = 0.05) and remained essentially unaltered after multivariable adjustments (hazard ratio 2.65, 95% CI 1.30-5.41 in those with better glycaemic control and hazard ratio 1.20, 95% CI 0.93-1.56 in those with worse glycaemic control).

These results suggest that, although better control may reduce the incidence of coronary artery disease in Type 1 diabetes, a residual risk related to the haptoglobin 2 allele remains.