There is now strong evidence that good control of glucose, blood pressure and cholesterol levels substantially improves outcomes in diabetes, as Dr John Clark explains

There have been two landmark studies in diabetes, which have provided valuable information on the degree of control that has to be achieved in order to prevent complications.

The Diabetes Control and Complications Trial,1 published in 1993, showed that the risk of developing microvascular complications was substantially reduced in patients with Type 1 (insulin-dependent) diabetes mellitus if they achieved a glycosylated haemoglobin (HbA1c) of 7.5% or less.1
A strikingly similar result was obtained for patients with Type 2 (non-insulin-dependent) diabetes in the United Kingdom Prospective Diabetes Study (UKPDS), published in 1998, which reported reduced microvascular complications in a group of patients with HbA1c of 7% or less.2 Macrovascular complications (e.g. myocardial infarction) were also reduced, but just failed to achieve statistical significance.

We are therefore the first generation of doctors to be able to advise our patients on the level of glycaemic control they need to achieve to avoid complications. Most clinicians have simplified the study results and advise both Type 1 and Type 2 diabetes patients to aim for a HbA1c of 7.5% or less.

GPs caring for patients with diabetes should be aware of these target levels, particularly as the British Diabetic Association has circulated documents on the standard of care that patients can expect from their doctor to all patients with diabetes.

Considerable high quality information is now available on the levels of blood pressure (BP) we should be aiming to achieve in our patients.

The UKPDS demonstrated that macrovascular complications were clearly reduced in patients who achieved a BP of 140/80mmHg.3 Intensive control of BP reduced the incidence of all macrovascular (non-fatal and fatal) complications by 34%, stroke by 44%, and myocardial infarction by 21%. There was also a 37% reduction in microvascular complications. Diabetes-related deaths were reduced by 32%. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers were equally effective.

The Hypertension Optimal Treatment (HOT) trial also reported in 1998. In the subgroup of patients with hypertension and diabetes, antihypertensive treatment aiming for a diastolic BP 80QmHg significantly reduced all major (non-fatal and fatal) cardiovascular events by 51% compared with treatment aiming for a diastolic BP of 90mmHg.4

The Joint British Recommendations on Prevention of Coronary Heart Disease in Clinical Practice,5 published in December 1998, suggest that together the UKPDS and HOT trial results support antihypertensive treatment of all patients with Type 2 diabetes and BP 160mmHg, aiming for a target BP of 130mmHg systolic and 80mmHg diastolic.

For patients with Type 2 diabetes and systolic BP 140–159mmHg but diastolic pressure 90mmHg, treatment is recommended if target organ damage, or microvascular or macrovascular complications are present, or if the absolute coronary risk is 15% over 10 years.5

Two or three drugs may be required to achieve this degree of control.

Since 1993 there have been three studies on secondary prevention6–8 and two on primary prevention9,10 confirming a substantial reduction in heart attacks and strokes in people treated with statins, up to age 75.

Although none of the studies was specifically designed to look at cholesterol-lowering treatment in diabetes, most included a few hundred patients with diabetes in their treatment groups. Subsequent analysis has shown that patients with diabetes did as well as, if not better than, those without diabetes.

Most clinicians would now treat any patient with diabetes who has coronary heart disease (CHD) with a statin, irrespective of his/her cholesterol level, given the substantial reduction in mortality demonstrated in these studies.

In patients with diabetes without CHD, there should be a low threshold for starting treatment, in view of their increased cardiovascular risk. If they also have hypertension or a family history of ischaemic heart disease, the threshold should be even lower. A total cholesterol of <5.0mmol/l is the target recommended in high-risk patients by the Joint British Recommendations on Prevention of Coronary Heart Disease in Clinical Practice.5

Future studies should provide us with guidelines on when to start statins in people with diabetes for primary prevention, but I estimate that a cholesterol level of 6.0mmol/l in patients over 40 years of age will possibly be chosen.

It now seems clear that by actively managing glucose, BP and cholesterol levels, the outcome for patients with diabetes can be substantially improved. GPs should continue to supervise patients with diabetes in whom these three variables are under good control, or in whom they can be brought under control, irrespective of whether the patient is receiving insulin treatment or on oral hypoglycaemic agents.

However, if this proves difficult, then referral to a diabetes specialist, for either hospital follow-up or joint care, should be arranged.

(1) Diabetes Control and Complications Trial (DCCT) Research Group. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-86.

(2) United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes. UKPDS (33). Lancet 1998; 352: 837-53.

(3) United Kingdom Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in Type 2 diabetes. Br Med J 1998; 317: 703-13.

(4) Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet 1998; 351: 1755-62.

(5) Joint British Recommendations on Prevention of Coronary Heart Disease in Clinical Practice. Heart 1998; 80(Suppl): S1-S29.

(6) The Scandinavian Simvastatin Study (4S). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet 1994; 344: 1383-9.

(7) Lewis SJ et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the CARE trial. Ann Intern Med 1998: 129(9): 681-9.

(8) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels (The Lipid Study). N Engl J Med 1998; 339: 1349-57.

(9) Shepherd J et al. Prevention of coronary heart disease with pravastatin in men with hyper-cholesterolaemia. N Engl J Med 1995; 333: 1301-7.

(10) Downs JR et al. Primary prevention of acute coronary event with lovastatin in men and women with average cholesterol levels. Results of AFCAPS/TEXCAPS Study. JAMA 1998; 279: 1615-22.

Guidelines in Practice, June 2000, Volume 3
© 2000 MGP Ltd
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