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BMJ. Aug 12, 2000; 321(7258): 405–412.
PMCID: PMC27454

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

Irene M Stratton, senior statistician,a Amanda I Adler, epidemiologist,a H Andrew W Neil, university lecturer in clinical epidemiology,b David R Matthews, consultant diabetologist,c Susan E Manley, biochemist,a Carole A Cull, senior statistician,a David Hadden, consultant physician,d Robert C Turner, director,e and Rury R Holman, directora on behalf of the UK Prospective Diabetes Study Group

Abstract

Objective

To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.

Design

Prospective observational study.

Setting

23 hospital based clinics in England, Scotland, and Northern Ireland.

Participants

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.

Outcome measures

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.

Results

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.

Conclusions

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%).


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