HbA_1c as predictor of all-cause mortality in individuals at high risk of diabetes with normal glucose tolerance, identified by screening: A follow-up study of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION), Denmark

Aims/hypothesis: Stepwise screening for type 2 diabetes will not only identify people with the disease or some other form of dysglycaemia (impaired fasting glucose or impaired glucose tolerance), but also many individuals who are phenotypically at high risk of developing diabetes, but currently have normal glucose tolerance (NGT). We therefore sought to assess whether HbA _1c adds prognostic information in relation to all-cause mortality in people who have NGT and a high risk of type 2 diabetes mellitus. Methods: In a Danish population-based stepwise screening programme for type 2 diabetes mellitus in general practice, we identified 15,634 persons at high risk of type 2 diabetes, who had NGT and a recorded HbA_1c measurement. As comparison groups, we included 1,401 people identified as having type 2 diabetes mellitus and 8,149 individuals characterised as being at low risk of diabetes. All individuals were followed from time of screening (April 2001 to December 2006) until death or 31 October 2009. Excess mortality was estimated using Cox proportional hazard models with all-cause mortality as the outcome measure. Results: Compared with individuals with NGT and HbA_1c below 6.0%, adjusted hazard ratios were: 1.21 (95% CI 0.95-1.56) for individuals with NGT and HbA_1c between 6.0% and 6.5%; 2.48 (95% CI 1.23-4.99) for individuals with NGT and HbA_1c 6.5% or above (in this group there were eight deaths among 68 individuals); 1.73 (95% CI 1.40-2.13) for individuals with type 2 diabetes mellitus. Conclusions/interpretation: HbA_1c level in people with NGT and at high risk of diabetes was clearly associated with increased all-cause mortality.