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Diabetes and coronary artery disease: time to stop taking the tablets?
  1. Departments of Cardiology and Medicine,
  2. University Hospital Birmingham NHS Trust,
  3. The Queen Elizabeth Hospital,
  4. Edgbaston, Birmingham B15 2TH, UK

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Patients with diabetes develop accelerated coronary artery disease and are 10 to 20 times overrepresented among those suffering from acute myocardial infarction.1 ,2 Mortality in the year following infarction is up to twice that of non-diabetics, and coronary artery disease remains the most common single cause of death in diabetic patients.3

Despite the wide prevalence of diabetes and its high rate of coronary artery disease, it remains unclear how diabetic patients with this complication should best be treated. An emerging concern is that standard treatments for the million or so non-insulin dependent diabetic patients in the UK may be contributing to the considerable morbidity and mortality from cardiovascular disease. These patients are most commonly treated with oral hypoglycaemic agents, usually sulphonylureas. Concern about such treatment, particularly sulphonylureas, has been expressed intermittently for nearly 30 years.4-7 Such concerns have become increasingly focused recently because of improved understanding of the molecular mechanisms of action of sulphonylureas, accumulating evidence of the superiority of insulin in treating diabetic patients following acute myocardial infarction,8 the clinical availability of potassium channel opening agents, and reminders of the hazards of biguanide treatment.

During conditions of low intracellular ATP concentration, including ischaemia, an ATP sensitive potassium (KATP) channel opens in the cell membrane of myocardial and arterial smooth muscle cells. This results in reduced myocardial contractility and increased arterial vasodilatation. Pancreatic β cells also contain KATPchannels and the hypoglycaemic action of sulphonylureas is dependent on KATP channel closure: indeed these agents are regarded as prototypical antagonists. In animal studies sulphonylureas cause coronary vasoconstriction with consequent myocardial ischaemia, and opening KATP channels pharmacologically has been shown in many models to confer protection during myocardial ischaemia.5 Such benefit probably derives, at least in part, from reducing contractility and increasing …

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