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UKPDS · United Kingdom Prospective Diabetes Study
Breakthrough in Approach to Type 2 Diabetes Treatment
The UK Prospective Diabetes Study has shown conclusively that:
  • Intensive therapy to reduce glycaemia is worthwhile as it reduces risk of complications.
  • Tight blood pressure control is worthwhile as it reduces risk of complications.
  • There are no major differences between the therapies tested.
  • Reduction in risk of complications of diabetes is a realizable goal.

The results of the United Kingdom Prospective Diabetes Study (UKPDS) were presented on the 10th and 11th of September at the European Association for the Study of Diabetes (EASD) Annual Meeting, Barcelona, 1998. The UKPDS is the largest clinical study of diabetes ever done. The unique, long-term 20-year study involving 5000 people with Type 2 diabetes was organized by the Diabetes Research Laboratories at Oxford, and led by Professors Robert Turner and Rury Holman. It commenced in 1976 and finished at the end of 1997. It cost £23 million.

The study itself was divided up into two main sections: the Glucose Control Study and the Blood Pressure Control Study. The questions asked in the Glucose Control Study were as follows:
  • Does an intensive glucose control policy reduce the risk of complications of diabetes?
  • Does insulin or sulphonylurea therapy have specific advantages or disadvantages?
  • Does metformin in overweight people with diabetes have any advantages or disadvantages?

The questions asked in the Blood Pressure Control Study were:
  • Can tight blood pressure control reduce morbidity and mortality in people with Type 2 diabetes?
  • Do ACE inhibitors or beta blockers have any specific advantages or disadvantages?
The UKPDS also finally set up a framework for the potential implications these results will have for the clinical care of people with diabetes.


Why was this Necessary?

The Diabetes Control and Complications Trial (DCCT) involved 1441 participants with Type 1 diabetes. Until now, this has been the most important study in the field of diabetes. This proved that with intensive therapy (strict glycaemic control) eye disease could be reduced by a factor of up to 72%, kidney disease by up to 60%, nerve damage by up to 48%, and major cardiac events by up to 78%. As a result of this study, intensive therapy has become the recognized method of treatment for Type 1 diabetes.

The UKPDS holds as much significance for Type 2 diabetes as the DCCT does for Type 1 diabetes. It will give the clinician the reassurance of a substantial foundation on which to treat individuals with diabetes.


Results

The UKPDS revealed that better blood glucose control reduces the risk of major diabetic eye disease by 25% and early kidney damage by apoproximately 33%, and that better blood pressure control reduces the risk of death from long-term complications of diabetes, strokes, and visual deterioration each by a factor of approximately 33%.


Better Blood Glucose Control

The intensive glucose control policy maintained a lower HbA1c level by a mean value of 0.9% over a median follow-up of ten years from diagnosis of Type 2 diabetes.

The UKPDS has shown that intensive blood glucose control reduces the risk of diabetic complications, the greatest effect being on microvascular complications.


Medical Therapy

One would now assume that if controlling glucose is advantageous, then any medical therapy that helps in the control of blood glucose would likewise be of advantage.

There were three main medical combinations that were tested in this study. Therapy using just diet alone (conventional) and therapy using sulphonylurea (glibenclamide/chlorpropamide), with or without insulin (intensive). The effect of adding metformin to these therapies was also examined, especially for those overweight.

Conventional therapy was shown to be not as effective in controlling glucose as intensive therapy. Intensive therapy is therefore recommended because keeping blood glucose levels close to normal can significantly reduce the risk of complications such as loss of sight and kidney damage.

Metformin was shown to be beneficial in overweight people with diabetes, being effective in reducing complications, but the addition of metformin in people already being treated with sulphonylurea requires further study.


Blood Pressure Control Study

This part of the study found that keeping blood pressure as close to normal as possible (ie 144/82 mmHg) will reduce the risk of death from long-term complications of diabetes, especially heart disease and stroke.

The use of ACE inhibitors and beta blockers were equally effective in lowering mean blood pressure in hypertensive people with Type 2 diabetes and in reducing complications.


Implications

What can be drawn from this study? What is the significance of all this on diabetes treatment?

Basically, doctors, clinicans and care providers can now be confident in the fact that keeping blood glucose and blood pressure under good control will undoubtedly benefit the person with diabetes. The UKPDS showed that the combination of certain drugs is not such an issue. The main message that came out of the sudy is: whatever, or however, and in whatever combination the therapy is used, the end result is essential, ie, good management of blood glucose and blood pressure. Metformin was seen as beneficial for overweight people with diabetes. Beta blockers and ACE inhibitors each provide protection. There is no evidence of increased risk of complications for any single type of therapy.

'Polypharmacy' is the term used to define this sort of treatment. The UKPDS showed that, in terms of glycaemia, combinations of agents with different action will be needed, and more people with diabetes will require insulin. In terms of blood pressure, many people with diabetes will need three or more different types of agents.

The UKPDS also showed that by the time diabetes is diagnosed, approximately half of the people with Type 2 diabetes already have evidence of tissue damage.

The results of the UKPDS suggest that a formal screening programme should be set up to identify diabetes before symptoms occur.

Just to finish - a quote from Professor Turner at the EASD '98 announcement of the UKPDS results.

"We now know that the risk of complications of Type 2 diabetes can be reduced with a more intensive application of existing therapies to maintain good control of blood pressure and blood glucose. The study shows for the first time that a substantial improvement in health of people with Type 2 diabetes can be obtained. This will allow people with diabetes to look forward to the future with greater confidence. At present diabetic complications are often regarded as being a natural outcome of this chronic disease. The study shows definitively that good management […] does help to prevent complications."
Kristina Hawthorne
Managing Editor of the IDF Bulletin, journal of the International Diabetes Federation.
IDFBulletin Vol 43:6-10 February 1999
Publish Permission 080299 Leena Etu-Seppälä
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