Nazer Rakan I, Abalhassan Mohammed F, Alburikan Khalid A
Department of Cardiac Science, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Cardiovasc Diagn Ther. 2018 Aug;8(4):469-479. doi: 10.21037/cdt.2018.05.04.
Metformin is an oral antidiabetic agent belonging to the biguanide class of antidiabetics. Possible novel applications for metformin in cardiovascular disease might exist. The aim of this study was to verify a possible association between pre-operative metformin administration and protection against ischemia-induced liver injury in diabetic patients undergoing coronary artery bypass grafting (CABG) surgery.
A retrospective case-control series was conducted at a single center. Two hundred consecutive diabetic patients underwent isolated on-pump CABG during a 12-month span (July 2015 - July 2016). Metformin was uninterrupted in patients who took this drug prior to CABG; 68 patients were metformin users (34%) while 132 patients were taking other antidiabetic agents (66%). Liver enzymes and other organ markers were consecutively recorded daily for 7 days after surgery and expressed as medians with interquartile range (IQR).
Both the metformin and non-metformin group of patients had similar pre-operative demographic characteristics. The median (IQR) post-operative cardiac enzyme creatinine kinase (CK) MB fraction was significantly lower in the metformin group [46.4 U/L (35.8-66.5) 66.5 U/L (44-94.5), P=0.005]. Total bilirubin [0.58 (0.48-0.82) mg/dL 0.67 (0.56-0.95) mg/dL, P=0.021], the transaminase aspartate aminotransferase (AST) [32.5 U/L (25.0-42.0) 37.5 U/L (28.5-56), P=0.011], the transaminases alanine aminotransferase (ALT) [48.5 U/L (40.0-64.0) 57.0 U/L (44.0-77.0), P=0.040] and lactate dehydrogenase (LDH) [320.0 U/L (273.5-367.2) 356.5 U/L (289.5-427), P=0.014] were significantly lower in the metformin group. No differences were noted in clinical outcomes.
In this limited retrospective study, the diabetic patients who took metformin before and after undergoing CABG appeared to have a reduced post-operative surge in the total bilirubin and transaminase liver enzymes. Metformin's role in mitigating oxidative stress in liver cells might explain this observation. Further experimental studies are warranted to verify this possible effect.
二甲双胍是一种口服抗糖尿病药物，属于双胍类抗糖尿病药。二甲双胍在心血管疾病中可能存在新的应用。本研究的目的是验证术前给予二甲双胍与接受冠状动脉旁路移植术（CABG）的糖尿病患者缺血性肝损伤保护之间可能存在的关联。
在单一中心进行了一项回顾性病例对照研究。在12个月期间（2015年7月至2016年7月），200例连续的糖尿病患者接受了单纯体外循环下的CABG。在CABG之前服用该药物的患者中，二甲双胍未中断使用；68例患者为二甲双胍使用者（34%），而132例患者正在服用其他抗糖尿病药物（66%）。术后连续7天每天记录肝酶和其他器官标志物，并表示为中位数及四分位数间距（IQR）。
二甲双胍组和非二甲双胍组患者术前的人口统计学特征相似。二甲双胍组术后心肌酶肌酸激酶（CK）同工酶MB分数的中位数（IQR）显著更低[46.4 U/L（35.8 - 66.5）对66.5 U/L（44 - 94.5），P = 0.005]。二甲双胍组的总胆红素[0.58（0.48 - 0.82）mg/dL对0.67（0.56 - 0.95）mg/dL，P = 0.021]、转氨酶天冬氨酸转氨酶（AST）[32.5 U/L（25.0 - 42.0）对37.5 U/L（28.5 - 56），P = 0.011]、转氨酶丙氨酸转氨酶（ALT）[48.5 U/L（40.0 - 64.0）对57.0 U/L（44.0 - 77.0），P = 0.040]和乳酸脱氢酶（LDH）[320.0 U/L（273.5 - 367.2）对356.5 U/L（289.5 - 427），P = 0.014]均显著更低。临床结局方面未发现差异。
在这项有限的回顾性研究中，接受CABG前后服用二甲双胍的糖尿病患者术后总胆红素和转氨酶肝酶的升高似乎有所减少。二甲双胍在减轻肝细胞氧化应激中的作用可能解释了这一观察结果。有必要进行进一步的实验研究来验证这种可能的作用。
