INTRODUCTION
Type 2 diabetes mellitus has emerged as the leading metabolic disorder worldwide, affecting more than 350 million individuals as of 2007. India is the ‘diabetic capital’ of the world, with 41 million people afflicted with the disease. The clinical importance of diabetes lies mainly in its propensity to produce macrovascular and microvascular complications, leading to cardiovascular disease, cerebrovascular disease, retinopathy, nephropathy, neuropathy and foot problems, which account for considerable morbidity and mortality throughout the world.
   Two landmark clinical trials—the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS)—established beyond doubt the importance of tight glycaemic control in preventing or delaying the complications of diabetes. Maintaining good control of blood sugar, as evidenced by a glycated haemoglobin level of <7%, can reduce the risk of diabetic retinopathy and nephropathy to negligible levels. However, in these trials, a similar impressive reduction was not found in the case of macrovascular complications, namely, cardiovascular and cerebrovascular disease. This leads one to presume that a comprehensive programme of risk reduction, looking beyond just glycaemic control, would be needed in order to reduce cardiovascular events in people with diabetes. This is of particular relevance to India as Asian Indians have been found to have an extremely high prevalence of cardiovascular disease.

THE CONCEPT OF GLOBAL CARDIOVASCULAR RISK
An individual’s risk of developing cardiovascular disease depends on the presence or absence of a number of risk factors, hyperglycaemia being only one of them. These factors act either additively or multiplicatively to determine the global cardiovascular risk of the individual. The most important of these risk factors have been included in the definition of the metabolic syndrome. These are central obesity, dyslipidaemia, fasting hyperglycaemia and hypertension. In addition to these conventional risk factors, newer markers such as C-reactive protein and platelet activator inhibitor-1 (PAI-1) have also been the subject of intense study. No less important are behavioural factors such as smoking and physical activity. Any programme to reduce cardiovascular risk must target all these factors if it is to succeed.
   We focus on the control of ‘conventional’ risk factors in people with diabetes, as these have been found to contribute to >90% of the cardiovascular burden of risk.

LIPIDS
As a result of defects in insulin secretion and insulin action, patients with type 2 diabetes are at risk of developing an atherogenic lipid profile. The main features of the so-called ‘diabetic dyslipidaemia’ are:

1. Elevated levels of triglycerides

2. Low levels of high density lipoprotein (HDL) cholesterol

3. High, normal or low levels of low density lipoprotein (LDL) cholesterol, associated with an increase in the highly atherogenic small dense LDL particles.

   The lipid profile should be checked at least annually in persons with diabetes, and more often if not at the target levels (Table I).
   Lipid management aimed at lowering LDL cholesterol, raising HDL cholesterol and lowering triglycerides has been shown to reduce macrovascular disease and mortality in people with type 2 diabetes, particularly in those who have had prior cardiovascular events. Recent trials suggest that aggressive lowering of LDL to <70 mg/dl can lead to significant reduction in cardiovascular events. The following points may be kept in mind when treating diabetic dyslipidaemia.

1. Any patient with dyslipidaemia should be offered a trial of therapeutic lifestyle change. Exceptions include those with prior cardiovascular or cerebrovascular disease and an LDL >100 mg/dl, or those at risk of acute complications of hyper-lipidaemia (e.g. acute pancreatitis from hypertriglyceridaemia). In such people, pharmacotherapy should be initiated at the same time as therapeutic lifestyle change.

2. Improvement in glycaemic control can in itself lead to improvement in certain lipid levels (e.g. triglycerides).

3. Patients who fail to respond to a therapeutic lifestyle change are candidates for drug therapy. The primary goal of drug therapy is to reduce LDL to target levels. Statins are the drug of choice for this purpose. Other drugs that lower LDL include nicotinic acid, ezetimbe, bile acid sequestrants and fenofibrate.

4. If the HDL is low, niacin may be added to the regimen.

5. In those with elevated triglycerides and normal cholesterol levels, a fibrate would be the drug of choice.

TABLE I. Targets for lipid levels in people with diabetes

   The usual doses, contraindications and side-effects of the commonly used lipid-lowering agents are listed in Table II.
   In addition to their cholesterol-lowering effect, statins also have other beneficial (‘pleiotropic’) effects on atherogenesis (Table III).

1. Most patients need more than one drug to achieve target levels of blood pressure.

2. Initial drug therapy should be with a class of drugs proven to reduce cardiovascular events (angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARB], beta-blockers, diuretics and calcium-channel blockers).

   The dosage, side-effects and contraindications of the 5 common classes of antihypertensive drugs are listed in Table IV.

ANTIPLATELET AGENTS
Aspirin is recommended for all people with diabetes as primary or secondary prevention for cardiovascular events. Several trials have shown an up to 30% reduction in myocardial infarction rates and 20% reduction in stroke rates when aspirin is used.

1. Aspirin is indicated for secondary prevention in people with diabetes with a history of cardiovascular and cerebrovascular disease.

2. It is also recommended as primary prevention in people with type 2 diabetes who are above 40 years of age and in those who have additional cardiovascular risk factors such as family history, smoking, hypertension or dyslipidaemia.

3. Aspirin is not recommended for people below the age of
   21 years due to the risk of Reye syndrome.

4. Doses of aspirin from 75 to 325 mg/day have been used. It is best to treat with lower doses in order to minimize side-effects.

5. Those who are unable to tolerate aspirin may be candidates for other antiplatelet agents (e.g. clopidogrel).

6. Combination therapy with aspirin and clopidogrel may be considered in those with severe and progressive cardiovascular or cerebrovascular disease.

SCREENING FOR COMPLICATIONS OF DIABETES
Complications of diabetes account for most of the morbidity and mortality due to the disease. An important aspect of diabetes care beyond glycaemic control is to screen for these complications, so as to detect them at a stage when effective treatment can be instituted. Comprehensive screening for these complications includes the following:

1. Regular assessment of cardiovascular risk factors as described above.

2. Diagnostic cardiac stress testing in individuals with symptoms of cardiovascular disease or those with abnormal resting ECG. The role of stress testing in asymptomatic individuals with normal ECG is controversial.

3. Estimation of microalbuminuria, serum creatinine and estimated glomerular filtration rate (eGFR) at least annually, starting from 5 years after diagnosis for those with type 1 and at diagnosis for those with type 2 diabetes.

4. Annual dilated retinal examinations starting at diagnosis in type 2 diabetes and at 5 years after diagnosis in type 1 diabetes.

5. Detailed foot examination with assessment of sensation and pedal pulses at each visit.

   Any of these screening procedures should be performed more frequently if any abnormality is detected.

CONCLUSION
Type 2 diabetes has reached epidemic proportions in India. The large number of people with diabetes in India translates into a huge population at risk for complications of diabetes. The most important aspect of diabetes care is the maintenance of tight glycaemic control. Nevertheless, to be successful, a diabetes care programme must look beyond glycaemic control and address each of the cardiovascular risk factors prevalent in the community. Such an approach alone can bring about a long-lasting reduction in the prevalence of complications of diabetes.

Madras Diabetes Research Foundation and Dr Mohan’s Diabetes Specialities Centre,
 4, Conran Smith Road, Gopalapuram,
Chennai 600086,
 Tamil Nadu, India