Mean HbA_1c and mortality in diabetic individuals with heart failure:a population cohort study

Aims: Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline HbA1c. Using time-weighted mean of serial HbA1c measures has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF. Methods: A time-weighted mean HbA1c was calculated using all HbA1c measures following CHF diagnosis. Patients were grouped into five categories of HbA1c (≤6.0%, 6.1-7.0%, 7.1-8.0%, 8.1-9.0 and >9.0%). The relationship between time-weighted mean HbA1c and all-cause deaths after CHF diagnosis was assessed. Results: 1,447 patients with T2DM met study criteria. During a median follow up of 2.8 years, there were 826 (57.1%) deaths with a crude death rate of 155 deaths per 1000 person-years (95% CI, 144-166). Cox regression model, adjusted for all significant predictors, with the middle HbA1c category (7.1-8.0%) as the reference, showed a U-shaped relationship between HbA1c and outcome [ HR(95% CI)]: HbA1c<6.0 %: HR(95%CI) 2.5(1.8-3.4); HbA1c 6.1-7.0%: HR(95%CI) 1.4(1.1-1.7); HbA1c 8.1-9.0%: HR(95%CI) 1.3(1.0-1.6) and HbA1c>9.0%: HR(95%CI) 1.8(1.4-2.3). Further analysis revealed a protective effect of insulin sensitizers (ie. metformin) [HR (95%CI) 0.75(0.61-0.93)] but not other drug classes. Conclusions: In patients with T2DM and CHF, our study shows a U-shaped relationship between HbA1c and mortality with the lowest risk in patients with modest glycaemic control (HbA1c=7.1-8.0%) and those treated with insulin sensitizes