BMJ 2001;322:15 ( 6 January )

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

Kay-Tee Khaw, professor of clinical gerontology, a Nicholas Wareham, Medical Research Council clinician scientist, a Robert Luben, research associate, computing and biostatistics, a Sheila Bingham, deputy director, b Suzy Oakes, research associate, a Ailsa Welch, research associate, nutrition, a Nicholas Day, Medical Research Council research professor. a

a Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge CB2 2SR, b Medical Research Council Dunn Human Nutrition Unit, Cambridge CB2 2XY

Correspondence to: K-T Khaw, Clinical Gerontology Unit, Box 251, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ kk101{at}medschl.cam.ac.uk

Objective: To examine the value of glycated haemoglobin (HbA1c) concentration, 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 and Nutrition (EPIC-Norfolk).
Subjects: 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999.
Main outcome measures: Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes.
Results: Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA1c concentration. HbA1c was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA1c concentrations below 5%. An increase of 1% in HbA1c was associated with a 28% (P<0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and 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 HbA1c concentration >= 7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA1c concentration >= 5% occurred 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 factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA1c through behavioural means.


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  • Tuomilehto, J. (2002). Point: A Glucose Tolerance Test Is Important for Clinical Practice. Diabetes Care 25: 1880-1882 [Full text]  
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Rapid Responses:

Read all Rapid Responses

Optimal range for HgA1C
John S Muchmore
bmj.com, 9 Jan 2001 [Full text]
Confounding Variables?: Insulin levels; Insulin Resistance
Paul Mele
bmj.com, 9 Jan 2001 [Full text]
HbA1c - treating the cause or the symptom?
Malcolm Macleod
bmj.com, 11 Jan 2001 [Full text]
Re: Confounding Variables?: Insulin levels; Insulin Resistance
Davina Edwards
bmj.com, 12 Jan 2001 [Full text]
Questioning the A1c
S Rievman
bmj.com, 13 Jan 2001 [Full text]
Correction to Table 3 in article
Kay-Tee Khaw
bmj.com, 14 Jan 2001 [Full text]
Psychosocial stress may be a cause of increased HbA1c
Peter Schuck
bmj.com, 18 Jan 2001 [Full text]
Analytical information is required to enable generalisation of data
Edmund Lamb
bmj.com, 19 Jan 2001 [Full text]
Is Glycated haemoglobin a risk factor for erectile dysfunction?
Masood Khan
bmj.com, 19 Jan 2001 [Full text]
Glycated haemoglobin, diabetes, and explanations
Vasiliy Vlassov
bmj.com, 27 Jan 2001 [Full text]

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