Effects of sulfonylureas on left ventricular mass in type 2 diabetic patients

Myocardial ATP-sensitive potassium (K_ATP) channels have been implicated in attenuating cardiac hypertrophy by modulating endothelin-1 concentrations. Sulfonylureas differ in their affinity for cardiac K _ATP channels and therefore may vary in their effects on left ventricular (LV) mass. We sought to determine the differential effects of sulfonylureas on LV mass in type 2 diabetic patients. All patients had been taking glibenclamide for more than 3 mo before being randomized to either switch to an equipotent dose of gliclazide or continue glibenclamide. A total of consecutive 240 diabetic patients were randomized into glibenclamide, gliclazide, a combination of glibenclamide and nicorandil, or gliclazide and nicorandil for 6 mo. In the gliclazide-treated group, the LV mass index was significantly decreased compared with that in the glibenclamide-treated groups. Nicorandil administration significantly reduced LV mass in glibenclamide-treated patients compared with patients treated with glibenclamide alone. Measurements of endothelin-1 concentrations mirrored the functional status of K_ATP channel. Multivariate analysis revealed that regression of LV mass was significantly correlated only with the changes in endothelin-1 (P <0.0001). Our results show that K_ATP channels may play a pathogenetic role, probably through an endothelin-1-dependent pathway, in diabetes mellitus-related ventricular hypertrophy. Patients treated with gliclazide may have a beneficial effect in attenuating ventricular mass.