Controversies in Management of Diabetes in Patients with Coronary Heart Disease

A global epidemic of type 2 diabetes exists and in the near future it may be closely associated with an epidemic of cardiovascular disease. Since the diabetic population is at risk of developing cardiovascular disease, diabetes management should target tight glycaemic control. Two controversial issues in the management of diabetics with coronary heart disease (CHD) are discussed in this review. Firstly, exogenous insulin administration and increased risk of cardiovascular disease, and, secondly, the effect of sulphonylurea treatment on potassium ATP channels and risk of myocardial ischaemia. The consensus of opinion is that high circulating serum insulin level is simply a marker of an insulin-resistant state and therefore does not have a direct role in the pathogenesis of atherosclerosis in diabetic patients. However, overwhelming evidence exists for the linear association between worsening glycaemic control and increased risk for coronary heart disease. The United Kingdom Prospective Diabetes Study reported intensive blood glucose control decreased the risk of myocardial infarction by 16%. The benefits of tight glycaemic control outweighs the theoretical concept of hyperinsulinaemia being atherogenic. Safety concerns about sulphonylureas date back to 1970. The mechanism of action of sulphonylureas by closure of potassium ATP channels identified in pancreatic beta cells, cardiomyocytes and vascular smooth muscle cells caused great concern about safety because of the risk of developing myocardial ischaemia. Brief episodes of cardiac ischaemia render the heart more resistant to subsequent ischaemic events, this phenomenon is called 'ischaemic preconditioning'. Activation of potassium ATP channels completely mimicked the preconditioning phenomena; moreover, blocking these channels with some of the sulphonylurea compounds abolished this protective effect. The concept of selectivity of sulphonylurea compounds therefore emerged and the choice of drug should be based on this fact. Every compound should be studied individually for its efficacy and safety vis-à-vis the relevant end points for type 2 diabetes, i.e. cardiovascular morbidity and mortality.