Are there benefits to switching from sulphonylureas to insulin after coronary artery bypass grafting?

Sulphonylureas help to control blood glucose levels by binding to adenosine-5-triphosphate(ATP)-sensitive potassium channels (KATP-channels) in the beta-cells of the pancreas. This inhibits potassium flux across the cell membrane, leading to depolarisation of the plasmalemma and subsequently the release of endogenous insulin. These same KATP-channels are also found in the myocardium and in vascular smooth muscle cells and are therefore implicated in the regulation of the cardiovascular
system.

A fall in myocardial cytosolic levels of ATP and a rise in extracellular adenosine opens the KATP-channels during myocardial ischaemia. This is thought to be a natural protective action, related to the phenomena of preconditioning and hibernation. Glibenclamide abolishes this effect at clinically relevant doses and infarct size is increased in animal models of myocardial ischaemia. These drugs also antagonise the vasodilating effects of drugs like minoxidil and diazoxide and can reduce resting myocardial blood flow. In contrast, sulphonylureas might reduce the incidence of post-ischaemic ventricular arrhythmias. By blocking KATP-channels, they prevent the tendency towards shortening of the action potential during myocardial ischaemia secondary to potassium efflux through opened channels.

Secondly, since type II diabetics are both insulin deficient and insulin resistant, glycaemic control may be improved in some individuals by combining oral medication with insulin or by switching completely.

In summary there remain theoretical arguments for and against changing from sulphonylureas following coronary surgery. The position may be eased by the development of more pancreas-specific drugs. For the time being at least, strict glycaemic control by whatever means should remain the primary aim, if necessary using short acting, low dose sulphonylurea derivatives.