The United Kingdom Prospective Diabetes Study (UKPDS), the largest and longest clinical study of diabetes ever attempted, recruited more than 5,000 patients with newly diagnosed type 2 diabetes in 23 centers within the U.K. between 1977 and 1991. Patients were followed for an average of 10 years to determine (among other endpoints) whether intensive use of pharmacological therapy to lower blood glucose would result in clinical benefits such as reduced cardiovascular and microvascular complications. In addition, patients with type 2 diabetes who were also hypertensive were randomized to "tight" or "less tight" blood pressure control to ascertain the benefits of lowering blood pressure.
The UKPDS revealed that better blood glucose control reduces the risk of major diabetic eye disease by a quarter, and of early kidney damage by one third. The results suggest that diabetic retinopathy, nephropathy and possibly neuropathy can be alleviated by lowering blood glucose levels with intensive therapy, which achieved a median HbA1c of 7.0% compared with conventional therapy with a median HbA1c of 7.9%. The overall microvascular complication rate was decreased by 25%. These findings augment the evidence that hyperglycemia causes, or is the major contributor, to such complications. Epidemiological analysis of the UKPDS data showed a continuous relationship between the risks of microvascular complications and glycemia, such that for every percentage point decrease in HbA1c (e.g., from 9% to 8%), there was a 35% reduction in the risk of complications. Additionally, the results demonstrated that the risks of complications can be significantly lowered even in the range of hyperglycemia where HbA1c levels are less than 8%.
No significant effect of lowering blood pressure on cardiovascular complications was observed, although epidemiological analysis showed a continuous association between the risk of such complications and glycemia, such that for every percentage point decrease in HbA1c, there was a 25% reduction in diabetes-related deaths, a 7% reduction in all-cause mortality, and an 18% reduction in combined fatal and nonfatal myocardial infarction. The study showed that lowering blood pressure to a mean of 144/82 mmHg significantly reduced strokes, diabetes-related deaths, heart failure, microvascular complications and visual loss.
The UKPDS demonstrated that vigorous treatment of diabetes can decrease the morbidity and mortality of the disease by decreasing its chronic complications. Lowering blood glucose was found to reduce the incidence of microvascular complications in type 2 diabetes as it does in type 1 diabetes.
Selected Publications
UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of both macrovascular and microvascular complications in type 2 diabetes (UKPDS 39). Br Med J 1998;317:713-720.
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38). Br Med J 1998;317:703-713.
UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-865.
UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853.
Ferris FL III, Davis MD, Aiello LM. Treatment of diabetic retinopathy. N Engl J Med 1999;341:667-678.
Click on the highlighted citations for summaries of studies
The Wisconsin Epidemiologic Study
Diabetes Control and Complications Trial Research Group
Early Treatment Diabetic Retinopathy Study Research Group
The Diabetic Retinopathy Study Research Group
Diabetic Retinopathy Vitrectomy Study Research Group
This web resource is made possible through an unrestricted educational grant from Eli Lilly and Company.
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