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Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study
Douglas H J Elder1, Jagdeep S S Singh1, Daniel Levin1
1Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Insights
Glycemic control in type 2 diabetes mellitus (T2DM) and heart failure (CHF) shows a U-shaped relationship with mortality. Modest HbA1c levels (7.1-8.0%) and metformin use are associated with the lowest risk of death in T2DM patients with CHF.
Area of Science:
- Cardiology
- Endocrinology
- Diabetology
Background:
- Glycemic control is crucial for patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF).
- Previous studies using single baseline HbA1c measurements have yielded conflicting results on its importance.
- Time-weighted mean HbA1c better reflects long-term glycemic burden and may be a superior predictor of outcomes.
Purpose of the Study:
- To investigate the relationship between time-weighted mean HbA1c and all-cause mortality in a large cohort of patients with T2DM and incident CHF.
- To determine the optimal glycemic control range for reducing mortality in this patient population.
- To assess the impact of different glucose-lowering medications on mortality risk.
Main Methods:
- A retrospective cohort study of 1447 patients with T2DM and incident CHF.
- Time-weighted mean HbA1c was calculated using serial measurements post-CHF diagnosis.
- Cox regression models were used to assess the association between HbA1c categories and mortality, adjusted for covariates.
Main Results:
- A U-shaped relationship was observed between time-weighted mean HbA1c and all-cause mortality.
- The lowest mortality risk was associated with HbA1c levels of 7.1-8.0%.
- Higher mortality risks were observed for HbA1c <6.0%, 6.1-7.0%, 8.1-9.0%, and >9.0% compared to the reference group.
- Metformin use showed a protective effect (HR 0.7, 95% CI 0.61-0.93).
Conclusions:
- A U-shaped relationship exists between HbA1c and mortality in T2DM patients with CHF.
- Modest glycemic control (HbA1c 7.1-8.0%) is associated with the lowest mortality risk.
- Insulin sensitizers, such as metformin, may offer a protective effect against mortality in this population.
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 glycosyated haemoglobin (HbA1c ). Using the time-weighted mean of serial HbA1c measurements 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 And Results:
A time-weighted mean HbA1c was calculated using all HbA1c measurements 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 death after CHF diagnosis was assessed. A total of 1447 patients with T2DM met the 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% confidence interval (CI) 144-166]. A 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 [HbA1c <6.0%, hazard ratio (HR) 2.5, 95% CI 1.8-3.4; HbA1c 6.1-7.0%, HR 1.4, 95% 1.1-1.7; HbA1c 8.1-9.0%, HR 1.3, 95% CI 1.0-1.6; and HbA1c >9.0%, HR 1.8, 95% CI 1.4-2.3]. Further analysis revealed a protective effect of insulin sensitizers (i.e. metformin) (HR 0.7, 95% CI 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 sensitizers.
