Submitted on May 20, 2006
Accepted on August 21, 2006
Effects of Sulfonylureas on Left Ventricular Mass in Type 2 Diabetic Patients
Tsung-Ming Lee1, Mei-Shu Lin2, Chang-Her Tsai3, Chen-Ling Huang4, and Nen-Chung Chang4*
1 Department of Medicine, Taipei Medical University and Chi-Mei Medical Center, Tainan, Taiwan, Taiwan - Republic of China
2 Department of Pharmacy, National Taiwan University and Hospital, Taipei, Taiwan, Taiwan - Republic of China
3 Department of Surgery, E-DA Hospital and I-Shou University, Kaohsiung, Taiwan, Taiwan - Republic of China
4 Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan, Taiwan - Republic of China
* To whom correspondence should be addressed. E-mail: ncchang{at}tmu.edu.tw.
Myocardial ATP-sensitive potassium (KATP) channels have been implicated in attenuating cardiac hypertrophy by modulating endothelin-1 concentrations. Sulfonylureas differ in their affinity for cardiac KATP channels and therefore may vary in their effects on left ventricular (LV) mass. We sought to determine whether the differential effects of sulfonylureas on LV mass in type 2 diabetic patients. All patients had been taking glibenclamide for more than 3 months before being randomized to switch either an equipotent dose of gliclazide or to 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 months. In the gliclazide-treated group, the LV mass index was significantly decreased than that in glibenclamide-treated groups. Nicorandil administration significantly reduced LV mass in glibenclamide-treated patients compared with the glibenclamide-treated patients alone. Measurements of endothelin-1 concentrations mirrored the functional status of KATP channel. Multivariate analysis revealed that regression of LV mass significantly correlated only with the changes in endothelin-1 (P < 0.0001). Our results show that KATP 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.
