Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
Contributors: IMS selected the methodology, carried out the statistical analyses, coordinated the writing of the paper, and participated in the interpretation of results. AIA assisted with the writing of the paper and interpretation of results. HAWN, DRM, and DH participated in interpretation and revision of the paper. SEM managed the biochemical aspects and participated in interpretation and revision of the paper. CAC participated in preparation of the database and interpretation and revision of the paper. RCT and RRH were the principal investigators, planned and designed the study, and participated in interpretation and revision of the paper. RCT was also responsible for the initial draft of the paper. RRH is guarantor.
To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Prospective observational study.
23 hospital based clinics in England, Scotland, and Northern Ireland.
4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.
Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA1c adjusted for possible confounders at diagnosis of diabetes.
The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA1c was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point.
In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA1c is likely to reduce the risk of complications, with the lowest risk being in those with HbA1c values in the normal range (<6.0%).
Person years, events, and unadjusted rates are for all patients.Click here to view.
The cooperation of the patients and many NHS and non-NHS staff at the centres is much appreciated. We thank Mr Dick Jelfs for the measurement of haemoglobin A1c. Details of participating centres can be found on the BMJ 's website.
Editorial by Tuomilehto
Professor Turner died unexpectedly after completing work on this paper
Funding: The major grants for this study were from the UK Medical Research Council, the British Diabetic Association, the UK Department of Health, The National Eye Institute and The National Institute of Digestive, Diabetes and Kidney Disease in the National Institutes of Health, United States, The British Heart Foundation, Novo Nordisk, Bayer, Bristol-Myers Squibb, Hoechst, Lilly, Lipha, and Farmitalia Carlo Erba. Details of other funding companies and agencies, the supervising committees, and all participating staff can be found on the BMJ's website.
Competing interests: AIA has received fees for speaking from Bristol-Myers Squibb, SmithKline Beecham, and Pfizer. IMS has received support for attending conferences from Zeneca and Hoechst and fees for speaking from Hoechst. CAC has received support for attending conferences from Bristol-Myers Squibb, Novo Nordisk, and Pfizer and fees for speaking from Bristol-Myers Squibb and Novo Nordisk. DRM has received fees for speaking from Bristol-Myers Squibb, Novo Nordisk, SmithKline Beecham, and Lilly and research funding from Lilly. SEM has received support for attending conferences from Bayer and Novo Nordisk. RRH has received fees for consulting from Bayer, Boehringer Mannheim, Bristol-Myers Squibb, Hoechst, Lilly, Novo Nordisk, Pfizer, and SmithKline Beecham; support for attending conferences from Bayer, Bristol-Myers Squibb, Hoechst, Lilly, Lipha, Novo Nordisk, and SmithKline Beecham; and research funding from Bayer, Bristol-Myers Squibb, Lilly, Lipha, and Novo Nordisk.
Details of participating centres, staff, and committees and additional funding agencies are on the BMJ's website.
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