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Reducing diabetes complications - Landmark study |
The UK prospective diabetes study (UKPDS) reported in The Lancet and BMJ last year establishes that better blood glucose control and blood pressure control reduces the risk of renal, eye and cardiovascular complications of type 2 diabetes. The study recruited 5,102 patients with newly diagnosed type 2 diabetes in 23 centres within the UK between 1977 and 1991. Patients were followed for an average of 10 years.
UKPDS randomised 3867 newly diagnosed patients between a conventional blood glucose control policy, keeping fasting plasma glucose <15 mmol/l, and an intensive glucose control policy, with sulphonylurea or insulin, aiming for fasting plasma glucose <6 mmol/l. More than 10 years follow-up HbA1c values of 7.9% and 7% in the conventional and intensive groups respectively were achieved. The intensive policy reduced the risk of:
- all diabetes related endpoints by 12% (microvascular, macrovascular and cataract extraction) (p=0.029)
- microvascular endpoints by 25% (predominantly retinal photocoagluation) (p=0.0099)
- myocardial infarction (borderline significant 16% risk reduction) (p=0.052)
- cataract extraction by 24% (p=0.046).
No increased incidence of cardiovascular deaths, myocardial infarction or sudden deaths was observed with sulphonylurea or insulin therapies, thus allaying previous fears that these agents may be harmful.
Metformin therapy in over-weight, diet-treated patients had advantages of :
- no weight gain,
- little increase in the risk of hypoglycaemia
- decreased risk of myocardial infarction.
The study further randomised 1148 people with hypertension in addition to their diabetes to a less tight blood pressure control policy or a tight blood pressure control policy achieving mean blood pressure levels of 154/87 mm Hg and 144/82 mm Hg respectively over 8.4 years. The tight blood pressure control policy reduced the risk of:
- any diabetes-related endpoints by 24% (p=0.0046)
- microvascular endpoints by 37% (p=0.0092)
- strokes by 44% (p=0.0013).
It also reduced deterioration of visual acuity by 47% (p=0.0036), suggesting less diabetic maculopathy, which is the major cause of blindness in Type 2 diabetes.
The two primary antihypertensive agents used, the ACE inhibitor captopril and the beta-blocker atenolol were similarly effective in reducing the risk of microvascular and macrovascular complications, suggesting it is blood pressure lowering, and not the specific therapy, that is important.
Epidemiological assessment of the incidence of microvascular and macrovascular endpoints of diabetes at increasing HbA1c or systolic blood pressure levels showed a log-linear relationship, indicating any reduction in glycaemia or blood pressure would be advantageous.
Many people with diabetes have both high blood glucose and blood pressure levels, and these patients are particularly at risk from diabetes complications.
The study data support previous guidelines and suggest one should aim for near-normal levels, aiming for targets for HbA1c <7% and blood pressure <140/80mmHg. To achieve this glycaemic target, more patients than at present will require combinations of oral agents and then insulin therapy. More than 30% of people with hypertension and diabetes will require three or more blood pressure lowering agents.
The UKPDS has shown also that raised LDL cholesterol and low HDL cholesterol and smoking are additional risk factors for myocardial infarction.
In summary, the UKPDS has shown that the complications of type 2 diabetes are not an inevitable outcome of the chronic disease, and that the risk can be reduced by appropriate therapy. Diabetes therapy is no longer mainly about glucose lowering per se, but about overall reduction in the risk factors for diabetic complications.
References available on request or check out: http://www.drl.ox.ax.uk.
Paul O'Brien is the GP manager of the diabetes project for the Northern Rivers Division of General Practice and is a GP in Bangalow, NSW, Australia.
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