Pan Nan-Hung, Lee Tsung-Ming, Lin Mei-Shu, Huang Chen-Ling, Chang Nen-Chung
Cardiology Section, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan.
Diabetes Res Clin Pract. 2006 Nov;74(2):121-8. doi: 10.1016/j.diabres.2006.03.009. Epub 2006 May 2.
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(2alpha) 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(2alpha) compared with baseline (299+/-101 pg/ml versus 400+/-112 pg/ml, P=0.001) and the glibenclamide-treated patients (299+/-101 pg/ml versus 388+/-114 pg/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(2alpha) 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(2alpha) (P<0.0001, adjusted R(2)=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.
糖尿病是一种氧化应激增加的状态，有证据表明氧化可能在左心室质量增加的发生过程中起作用。已证明格列齐特具有清除自由基的特性。我们评估了格列齐特是否可能通过降低8-异前列腺素F（2α）浓度（氧化损伤的可靠标志物）对左心室质量产生有益影响。总共41例患者被随机分为两组。所有患者在随机分组前已服用格列本脲3个月以上，随机改为服用等效剂量的格列齐特（n = 21）或继续服用格列本脲（n = 20）。两组的基线特征相似。6个月时，与格列本脲治疗组相比，格列齐特治疗的患者左心室质量指数显著下降（-16%对3%，P = 0.003）。与基线相比，格列齐特治疗的患者血浆8-异前列腺素F（2α）显著降低（299±101 pg/ml对400±112 pg/ml，P = 0.001），6个月治疗后与格列本脲治疗的患者相比也显著降低（299±101 pg/ml对388±114 pg/ml，P = 0.01）。左心室质量指数下降的幅度与8-异前列腺素F（2α）形成的抑制幅度单变量相关（r = 0.74，P < 0.0001）。多变量分析显示，左心室质量指数的下降与8-异前列腺素F（2α）的变化显著相关（P < 0.0001，调整后的R（2）= 0.55）。我们的研究结果首次表明，除了其主要的降血糖作用外，格列齐特可能还具有降低左心室质量的额外作用，可能是通过减少自由基形成来实现的。
