Editor,—We write in response to the editorial “Diabetes and coronary artery disease: time to stop taking the tablets”.1 The authors highlight previous studies where diabetic patients treated with sulphonylureas have an excess cardiovascular mortality during myocardial infarction compared with diabetic patients treated by other means. As Connaughton and Webber point out ischaemic preconditioning has refocused our attention on these trials.

The profound protective effects of ischaemic preconditioning are thought to be mediated by opening of a K_ATP channel, while the hypoglycaemic action of sulphonylureas is mediated by closure of these channels within the membrane of β cells in the islets of Langerhan. The authors suggest that it may be simply a case of “adding a potassium channel opener along with insulin during [myocardial infarction] MI” to improve outcome in diabetics presenting with infarction. However, recent findings suggest this is an oversimplification and probably incorrect.

One problem is that, there are at least two different K_ATP channels within cardiac myocytes. Evidence is emerging that it is the mitochondrial and not the cell membrane K_ATPchannels that initiates the cardioprotective effects of preconditioning. This conclusion is based on recent work from Marban’s group.2-4 These investigators show that …