Association of gliclazide and left ventricular mass in type 2 diabetic patients

Abstract 

Diabetes is a state of increased oxidant stress and there is evidence that oxidation may play a role in the genesis of higher left ventricular mass. Gliclazide has been shown to possess free radical scavenging properties. We assessed whether gliclazide may have a beneficial effect on left ventricular mass via reducing 8-iso-prostaglandin F_2α concentrations, a reliable marker of oxidant injury. A total of 41 patients were randomized into two groups. All patients had been taking glibenclamide for more than 3 months before being randomized to switch either an equipotent dose of gliclazide (n=21) or to continue on glibenclamide (n=20). Baseline characteristics were similar in both groups. At 6 months, gliclazide-treated patients showed a significant regression in left ventricular mass index compared with the glibenclamide-treated group (−16% versus 3%, P=0.003). Gliclazide patients had significantly lower plasma 8-iso-prostaglandin F_2α compared with baseline (299±101pg/ml versus 400±112pg/ml, P=0.001) and the glibenclamide-treated patients (299±101pg/ml versus 388±114pg/ml, P=0.01) after 6-month therapy. The magnitude of left ventricular mass index regression correlated univariately with the magnitude of inhibition of 8-iso-prostaglandin F_2α formation (r=0.74, P<0.0001). Multivariate analysis revealed that regression of left ventricular mass index significantly correlated with the changes of 8-iso-prostaglandin F_2α (P<0.0001, adjusted R²=0.55). Our findings demonstrated for the first time that in addition to its primary hypoglycemia, gliclazide may have an additional effect on reducing left ventricular mass, possibly through attenuation of free radical formation.

Keywords: 8-Iso-prostaglandin F_2α, Diabetes mellitus, Glibenclamide, Gliclazide, Left ventricular mass