HbA 1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus

Abstract

Introduction: Observational studies have shown that glycated haemoglobin (HbA 1c) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA 1c measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA 1c was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA 1c in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results: After a median follow-up of 9.3 years, 460 participants died. Higher HbA 1c was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity =0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA 1c and medication. Conclusion: This prospective study showed that persons with lower HbA 1c had better survival than those with higher HbA 1c. The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA 1c appears to be associated with reduced mortality risk. © 2012 Sluik et al.