THE UNITED KINGDOM PROSPECTIVE DIABETES STUDY: WHAT DOES IT TELL US?

The UKPDS is the largest and longest study on type 2 diabetic patients that has ever been performed. It recruited 5,102 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 1) whether intensive use of pharmacological therapy to lower blood glucose levels would result in clinical benefits (i.e., reduced cardiovascular and microvascular complications) and 2) whether the use of various sulfonylurea drugs, the biguanide drug metformin, or insulin have specific therapeutic advantages or disadvantages. 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 and to ascertain whether the use of an ACE inhibitor (captopril) or beta-blocker (atenolol) offered particular therapeutic advantages or disadvantages.

The UKPDS results establish that retinopathy, nephropathy, and possibly neuropathy are benefited by lowering blood glucose levels in type 2 diabetes 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%.

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., 9 to 8%), there was a 35% reduction in the risk of complications.

The results demonstrate that the risks of complications can be significantly lowered even in the range of hyperglycemia where HbA1c levels are <8.0%. There was no evidence of any glycemic threshold for any of the microvascular complications above normal glucose levels (i.e., HbA1c >6.2%).

These results confirm previous conclusions that lowering blood glucose would be beneficial based on observational studies, pathological studies, and on three randomized clinical trials: the DCCT, the Stockholm Diabetes Intervention Study, and the Japanese study.

For every percentage point decrease in HbA1c (e.g., 9 to 8%), 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. Again, no glycemic threshold for these complications above normal glucose levels was evident. 

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.