United Kingdom Prospective Diabetes Study (UKPDS)
Implications for the care of people with type 2 diabetes

The United Kingdom Prospective Diabetes Study (UKPDS), the largest clinical research study of diabetes ever conducted, has provided conclusive evidence that the life threatening complications of type 2 diabetes (non insulin dependent diabetes) can be significantly reduced by appropriate treatment. This study, in which the British Diabetic Association (BDA) invested over £2m, has shown that lowering raised blood glucose and blood pressure levels, with the more effective use of existing treatments, reduces the risk of heart disease, stroke and death from diabetes-related diseases as well as diabetic eye disease and early kidney damage. 

The UKPDS has irrefutably shown that the emphasis must be on achieving optimal blood pressure and blood glucose levels from the time of diagnosis. Effective therapy to attain these will reduce the risk of diabetes complications and they are necessary to maintain good health. 

It is now clear that type 2 diabetes is a progressive condition and must never be considered a 'mild' form of diabetes. It always needs to be taken seriously and the objective of treatment should be to achieve and maintain long term near-normal blood glucose and blood pressure levels. The time of diagnosis is a critical time for the individual to be told about both the potential impact of type 2 diabetes and the importance of treating it effectively. As a result of the UKPDS findings the BDA recommends treatment which aims for the following:

Blood pressure levels of 140/80 mm Hg or below  Fasting blood glucose levels of 4 - 7 mmol/litre 
HbA1c levels of 7.0% or below * Self monitored blood glucose levels before meals between 4 and 7 mmol/ 

 Doctors should consider assessing therapy when a single blood pressure, HbA1c or fasting blood glucose level is higher than the above. It is important to recognise that these levels may not be achievable for all patients. Individual patient targets need to be assessed in relation to age, general health and other risk factors. Even if the ideal levels cannot be reached despite maximal attempts to improve treatment, it is important to realise that any improvement in blood glucose or blood pressure levels will help to reduce the risk of complications. This is good news for people with diabetes. 

The study also shows that when diabetes is diagnosed, initial dietary advice has a major impact on weight and blood glucose control. Restriction of fat intake and replacement by high fibre foods, with calorie restriction in people who are overweight, is advised. Results should be assessed, possibly monthly, for three months. However, the study shows that in most people it was not possible to reduce the fasting blood glucose to below 7 mmol/litre with dietary and exercise advice alone. Other therapies, usually tablets, will then be required. 

The study has shown that each of the existing therapies for treating diabetes (metformin, sulphonylureas, acarbose and insulin) are effective in reducing glycaemia**. 

In those who are overweight (body mass index >25 kg/m2) metformin may be particularly advantageous, although the study showed that other therapies, eg acarbose or sulphonylureas, will often be required in addition to maintain target blood glucose levels. 

One of the most striking observations of the UKPDS is the progressive nature of type 2 diabetes. For people taking tablets it is often necessary to increase the dose, add other tablets or eventually to commence insulin treatment. The results of the UKPDS mean that combinations of therapies with different modes of action are likely to be used more often then previously. 

People with diabetes need to be informed that every few years additional therapies may have to be added including insulin. If the subject of a possible future need for insulin therapy is introduced early, peoples÷ concerns and fears can be addressed directly. They should be reassured when they need more therapy that it is not their fault that diabetes progressively worsens with time. People with diabetes taking insulin injections will also often require dosage increases over time to maintain glycaemic control. 

For treating blood pressure, the study has shown that beta-blockers and ACE inhibitors are equally effective in reducing the risk of diabetic complications. Other therapies such as diuretics can also be used to maintain target blood pressure levels. 

An essential element in the treatment of people with type 2 diabetes is ongoing, culturally appropriate education. This should ensure a good understanding of what the blood glucose and blood pressure targets and test results mean and how these targets may be achieved. With this information people with diabetes are better able to take responsibility for their own health. Psychological and social factors will play an important role in facilitating or preventing people from meeting these targets. It is also important that people are made aware of the potential increased risk of hypoglycaemia and weight gain when taking sulphonylurea or insulin treatment and that they are given advice on how to limit such risks. 

The recommended treatment aims may require people with diabetes to take more treatments than hitherto. Irrespective of the medications chosen, diet and exercise advice, together with avoidance of smoking, remain central elements of diabetes management. However, an individual assessment, which includes lifestyle aspects, is always essential in determining the most appropriate treatment. 

The study revealed that up to 50% of people newly diagnosed with type 2 diabetes already showed early signs of complications. This emphasises the need for early detection of diabetes and screening for diabetes of those in high risk groups, such as those who are over 40, those who are overweight, those of Asian or African-Caribbean origin, those who have a family history, or those with a prior history of gestational diabetes. 

The wider issue of screening for type 2 diabetes is being discussed by the National Screening Committee and the BDA is involved in these discussions. The BDA recommends that those people with type 2 diabetes should have regular consultations with their clinical team so that they can monitor their diabetes control and discuss the setting of targets. The frequency of these consultations will depend on individual circumstances but people may need to be seen quarterly. 

The UKPDS has shown that the additional cost of medication to improve blood pressure levels was directly recouped by a reduced cost of hospital admissions. In addition, the introduction of improved treatment did not appear to affect the quality of life, assessed by questionnaires, whereas macrovascular complications (predominantly heart attacks and strokes) and microvascular complications (predominantly retinopathy requiring photocoagulation) were thought to significantly reduce the quality of life. 

In order for people with type 2 diabetes to enjoy the potential benefits demonstrated by the UKPDS, diabetes care needs to be organised in a systematic and integrated way. This is likely to require more attention to blood glucose and blood pressure control by general practice teams. The BDA will continue to examine the implications of the UKPDS results and liaise with people with diabetes, healthcare professionals and the government to ensure that the messages from the study are fully incorporated into good clinical practice and that diabetes is recognised as a priority within the health service. 

* When measured with an assay aligned to the DCCT method, normal range 4.5 - 6.2%. For other assays the target HbA1c should be within 1% of the upper end of the laboratory÷s normal range.
** The results of the UKPDS sub study examining sulphonylurea and metformin combination therapy are the subject of a separate BDA statement. This concludes that the study did not provide sufficient evidence to suggest combined therapy with sulphonylurea and metformin should not be used, even though there was an apparent small increase in the proportion of patients who had died from stroke or myocardial infarction whilst on combined therapy. The BDA recommends that if a patient is well controlled on a combination of sulphonylurea and metformin then there is no reason to discontinue a successful treatment.

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