The haemoglobin glycation index as predictor of diabetes-related complications in the AleCardio trial

The haemoglobin glycation index (HGI) quantifies the interindividual variation in the propensity for glycation and is a predictor of diabetes complications and adverse effects of intensive glucose lowering. We investigated the relevance of HGI as independent predictor of complications by using data of the AleCardio trial. The AleCardio trial randomized 7226 type 2 diabetes patients with an acute coronary syndrome to aleglitazar or placebo. From 6458 patients with baseline glycated haemoglobin (HbA(1c)) and fasting plasma glucose (FPG), a linear regression equation, HbA(1c) (%)=5.45+0.0158 * FPG (mg/dl), was used to calculate predicted HbA(1c) and derive HGI (= observed - predicted HbA(1c)). With multivariate Cox regression we examined the association with major adverse cardiac events, cardiovascular mortality, total mortality and hypoglycaemia, irrespective of treatment allocation, using HGI subgroups (low, intermediate and high) and HGI as continuous variable. Patients with high HGI were younger, more often non-Caucasian, had a longer duration of diabetes, showed more retinopathy and used insulin more often. Hypoglycaemia occurred less often in the low HGI subgroup, but this difference disappeared after adjustment for duration of diabetes, insulin and sulphonylurea use. Low HGI patients were at lower risk for cardiovascular mortality (hazard ratio 0.64; 95% confidence interval 0.44-0.93, p=0.020) and total mortality (hazard ratio 0.69; 95% confidence interval 0.50-0.95, p = 0.025), as compared with high HGI patients. Every percentage increase in HGI was associated with a 16% increase in the risk for cardiovascular mortality (p=0.005). The association between HGI and mortality disappeared with additional adjustment for HbA(1c). HGI predicts mortality in diabetes patients with acute coronary syndromes, but no better than HbA(1c).