Statin prescribing and the type 2 diabetes timebomb
With heightened concern about the expected rise in type 2 diabetes,
Dr Roger Gadsby looks at the role statins can play in treatment
ype 2 diabetes is a public health timebomb that is set to explode in the UK. By 2010 the number of people with type 2 diabetes is expected to double. There is clearly a need for concerted action to manage this condition. NICE recently issued guidelines to support the care of type 2 diabetes, focusing on the management of blood
Hyperglycaemia is predictive of a high risk of serious eye, kidney, nerve and cardiovascular disease, notably coronary artery, peripheral vascular and cerebrovascular disease. Progressive increases in plasma glucose and the presence of other risk factors such as hypertension, hyperlipidaemia, albuminuria and smoking increase the risk even further. All of these risk factors are potentially modifiable and have been shown to reduce the risk of some or all of the complications of diabetes.
The United Kingdom Prospective Diabetes Study (UKPDS) showed clearly the importance of achieving optimising blood glucose levels; even a modest decrease of 1 per cent in haemoglobin A1c (HbA1c) lowers the risk of diabetes-related clinical endpoints, particularly eye and kidney disease. NICE therefore recommends monitoring of HbA1c at two- to six-monthly intervals, and recommends a target HbA1c level of between 6.5 and 7.5 per cent.
Controlling blood pressure
While improved glycaemic control is important, it should not be considered the sole therapeutic target in type 2 diabetes. Lipid and blood pressure control must not be overlooked since more than 50 per cent of people with diabetes die from coronary heart disease. There is also evidence that those with diabetes and no history of heart disease have the same risk of heart attack as people without diabetes who have already had a myocardial infarction.
There is clear evidence of the benefit from maintaining tight control of blood pressure to reduce the risk of stroke and myocardial infarction. In the UKPDS, tight control of blood pressure to a level of 140/80mmHg produced more dramatic reductions in macrovascular complications than did tight glycaemic control.
Significance of lipid lowering
Dyslipidaemia is also common in patients with diabetes, who can have normal levels of total and LDL-cholesterol but elevated levels of triglycerides and very low density lipoproteins (VLDLs) with low levels of HDL-cholesterol.
Although no lipid-lowering outcome trials have been conducted solely in a diabetic population, several of the major statin studies have included significant numbers of subjects with diabetes. Among the people with diabetes enrolled in the CARE study (secondary prevention people with 'average' cholesterol levels) the major coronary event was 37 per cent in placebo patients but 29 per cent in the group given pravastatin.
This finding has now been reinforced by the recent results of the Heart Protection Study, which showed that statin treatment in people with diabetes but no history of heart
disease and who had a total cholesterol level above 3.5mmol was associated with a revascularisation procedure
(P = 0.002).
Overall, the evidence from all of the statin intervention trials suggests that diabetic patients gain at least as much from treatment as non-diabetic patients. However, because their relative risk of CHD is two- to four-fold higher, the absolute benefit of treatment is likely to be greater.
Given recent concerns about the safety of statins, the long-term experience with both pravastatin and simvastatin is that these medications do not cause significant problems. Many people with diabetes will be taking a number of medications to control blood pressure and blood glucose.
Drug interactions can then become important. The fact that pravastatin has a low propensity to interact with commonly prescribed medications, because is not metabolised to any significant extent by the cytochrome p450 enzyme system, may then be an important consideration.
The compilers of the British recommendations on prevention of CHD and the national service framework for coronary heart disease identified patients with diabetes as priorities for lipid management. It is likely that the forthcoming NICE guidelines on the management of lipids in patients with diabetes will follow suit.
Equally, it is reasonable to assume that, like the NSF for coronary heart disease, it will endorse the use of those statins for which there is trial evidence of benefit in reducing both cardiovascular events and mortality rather than simply evidence of effective cholesterol lowering.
The emerging epidemic of type 2 diabetes requires concerted efforts to optimise blood glucose, blood pressure and dyslipidaemia. Treating all these risk factors may help to ameliorate the tide of diabetes complications over the next 10 years.
By 2010 the number of people with type 2 diabetes is expected to double~