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

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 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%).

Relationship of glycaemic control and hypoglycaemic episodes to 4‐year cardiovascular outcomes in people with type 2 diabetes starting insulin

“…These results are broadly in line with the less‐certain effects seen in major randomized trials, and they support the conclusion that improved glycaemic control reduces CV events 6, 17, 18. Participants were newly started on insulin and generally achieved and maintained reasonable glycaemic control during follow‐up in the study, with median HbA1c of 9.3% (78 mmol/mol) at baseline, declining to 7.4% (57 mmol/mol) at the end of year 1 and 7.3% (56 mmol/mol) at the end of year 4.…”

“…The ADVANCE study saw a 6% non‐significant reduction in MACE events associated with a 0.8% reduction in HbA1c 4. The relationship between HbA1c reduction and CV events in the UKPDS was also suggestive, but uncertain at study end, but again significant at the end of the extension phase (MI, all‐cause mortality), and in study observational analysis 17, 19, 22. Accordingly, the meta‐analyses of these studies also found statistically significant reductions in MI and overall CV events 18, 23.…”

Associations of Glycemic Control With Cardiovascular Outcomes Among US Hemodialysis Patients With Diabetes Mellitus

“…However, higher HbA 1c was a strong risk factor for sudden death, whereas no association was found between baseline HbA 1c and risks of fatal or nonfatal MI and heart failure death 33. Although the effect of tight glycemic control on microvascular complications has been well established,5, 28, 31, 34 its effect on macrovascular complications remains controversial, and more research is warranted to further study these relationships in patients on hemodialysis with DM. In this study we observed only moderate associations between higher HbA 1c and increased rates of cardiovascular mortality and MI.…”

Glycaemic control in the diabetes and Lifestyle Cohort Twente: A cross‐sectional assessment of lifestyle and pharmacological management on Hba1c target achievement

“…Each 1% of mean HbA1c reduction has been associated with a 21% reduction in risk of any diabetes‐related complication 1. In general, a target HbA1c level of <53 mmol/mol (<7%) is optimal, according to diabetes guidelines 2…”