Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk)

Objective To examine the value of glycated haemoglobin (HbA(1c)) concentrat ion, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. Design Prospective population study. Setting Norfolk cohort of European Prospective Investigation into Cancer an d Nutrition (EPIC-Norfolk). Subjects 4662 men aged 45-79 years who had had glycated haemoglobin measure d at the baseline survey in-1995-7 who were followed up to December 1999. Main outcome measures Mortality from all causes, cardiovascular disease, is chaemic heart disease, and other causes. Results Men with known diabetes had increased mortality: from all causes, c ardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P < 0.001 independent of age and other risk factors) com pared with men without known diabetes. The increased risk of death among me n with diabetes was largely explained by HbA(1c) concentration. HbA(1c) was continuously related to subsequent all cause, cardiovascular, and ischaemi c heart disease mortality through the whole population distribution, with l owest rates in those with HbA(1c) concentrations below 5%. An increase of 1 % in HbA(1c) was associated with a 28% (P < 0.002) increase in risk of deat h independent of age, blood pressure, serum cholesterol, body mass index, a nd cigarette smoking habit; this effect remained (relative risk 1.46, P = 0 .05 adjusted for age and risk factors) after men with known diabetes, a HbA (1c) concentration greater than or equal to 7%, or history of myocardial in farction or stroke were excluded. 18% of the population excess mortality ri sk associated with a HbA(1c) concentration greater than or equal to5% occur red in men with diabetes, but 82% occurred in men with concentrations of 5% -6.9% (the majority of the population). Conclusions Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk facto r through the whole population distribution. Preventive efforts need to con sider not just chose with established diabetes but whether it is possible t o reduce the population distribution of HbA(1c) through behavioural means.