Kay-Tee Khaw, MBBChir FRCP; Nicholas Wareham, MBBS, FRCP; Sheila Bingham, PhD; Robert Luben, BSc; Ailsa Welch, BSc; Nicholas Day, PhD
Acknowledgments: The authors thank the participants, general practitioners, and staff of EPIC–Norfolk.
Grant Support: EPIC–Norfolk is supported by program grants from the Medical Research Council United Kingdom and Cancer Research United Kingdom. The European Union, Stroke Association, and British Heart Foundation provided additional support.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Kay-Tee Khaw, MBBChir, FRCP, Clinical Gerontology Unit, Box 251, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Khaw: Clinical Gerontology Unit, Box 251, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom.
Dr. Wareham: Medical Research Council Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom.
Dr. Bingham: Medical Research Council Dunn Nutrition Unit, Wellcome Trust/Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom.
Mr. Luben, Ms. Welch, and Dr. Day: Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratories, Worts Causeway, Cambridge CB1 8RN, United Kingdom.
Author Contributions: Conception and design: K.-T. Khaw, N. Wareham, S. Bingham, A. Welch, N. Day.
Analysis and interpretation of the data: K.-T. Khaw, N. Wareham.
Drafting of the article: K.-T. Khaw, N. Wareham.
Critical revision of the article for important intellectual content: N. Wareham, S. Bingham, A. Welch, N. Day.
Final approval of the article: K.-T. Khaw, N. Wareham, S. Bingham, R. Luben, A. Welch, N. Day.
Statistical expertise: R. Luben, N. Day.
Obtaining of funding: K.-T. Khaw, N. Wareham, S. Bingham, N. Day.
Administrative, technical, or logistic support: N. Wareham, S. Bingham, R. Luben, A. Welch, N. Day.
Collection and assembly of data: R. Luben, A. Welch.
Khaw K, Wareham N, Bingham S, Luben R, Welch A, Day N. Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk. Ann Intern Med. 2004;141:413-420. doi: 10.7326/0003-4819-141-6-200409210-00006
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Published: Ann Intern Med. 2004;141(6):413-420.
Several studies suggest that blood glucose levels are associated with cardiovascular disease, even at blood glucose values that do not meet diagnostic criteria for diabetes.
Among adult residents of Norfolk, United Kingdom, there was a continuous relationship between hemoglobin A1c levels and cardiovascular disease and total mortality. This relationship was apparent even among persons without diabetes.
These observations justify the need for studies that address whether improvements in glycemic control might improve health outcomes in persons who do not have diabetes.
Diabetes mellitus is of major and increasing global public health importance (1). Persons with diabetes are at increased risk for premature disability and death associated with vascular, renal, retinal, and neuropathic complications. Raised fasting and postchallenge blood glucose levels in an oral glucose tolerance test are used to diagnose diabetes. The diagnostic threshold is based on the shape of the risk curve between glucose levels and specific microvascular complications of diabetes (2-6). Diabetes also increases the risk for macrovascular diseases, such as coronary heart disease and stroke (7). In contrast to microvascular disease, increasing evidence suggests that the relationship between blood glucose level and macrovascular disease is continuous and does not have an obvious threshold (2, 8, 9).
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