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 photocoagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA 1c 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 HbA 1c 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 HbA 1c is likely to reduce the risk of complications, with the lowest risk being in those with HbA 1c values in the normal range ( < 6.0%).

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