Diabetes Care Unit, Department of Internal Medicine, Catholic University School of Medicine, Rome, Italy.
Diabetes Obes Metab. 2013 May;15(5):427-31. doi: 10.1111/dom.12041. Epub 2012 Dec 5.
Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients.
Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed.
Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2) < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups.
Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.
多项研究调查了二甲双胍治疗 1 型糖尿病（T1DM）患者的效果。目前尚无研究检测其对这些患者内皮功能的影响。本研究旨在评估二甲双胍对 1 型糖尿病患者内皮功能的影响。
42 例无并发症的 T1DM 患者被随机分为安慰剂对照、双盲、6 个月的试验组，分别接受二甲双胍或安慰剂治疗。在基线和研究结束时测量血糖代谢和临床参数以及右侧肱动脉血流介导的扩张（FMD）和硝酸盐介导的扩张（NMD）。还评估了血糖变异性（GV，根据连续血糖监测数据计算）和氧化应激的生物标志物[尿 8-异前列腺素 F2α（PGF2α）]。
两组的基线数据相似。与安慰剂相比，二甲双胍显著降低体重[-2.27kg（95%置信区间：-3.99；-0.54）；p=0.012]，同时改善 FMD[1.32%（0.30；2.43）；p=0.013]和增加 PGF2α[149pg/mg 肌酐（50；248）；p=0.004]。值得注意的是，FMD 的改善与体重的降低无关（r(2) <1%）。两组治疗后，NMD、糖化血红蛋白 A1c、GV、每日胰岛素剂量和其他参数均无显著变化。
本试验表明，在无并发症的 1 型糖尿病患者中，二甲双胍改善 FMD 并增加 PGF2α，这是氧化应激的标志物，而与血糖控制和体重无关。需要进行随机、盲法临床试验来评估在 1 型糖尿病中添加胰岛素治疗的获益和风险。
