Anderson Jemma J A, Couper Jennifer J, Giles Lynne C, Leggett Catherine E, Gent Roger, Coppin Brian, Peña Alexia S
Discipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia.
Endocrinology and Diabetes Department, Women's and Children's Hospital, Australia.
J Clin Endocrinol Metab. 2017 Dec 1;102(12):4448-4456. doi: 10.1210/jc.2017-00781.
Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis. Early interventions are needed to reduce cardiovascular disease.
To evaluate the effect of metformin on vascular function in children with type 1 diabetes.
Twelve-month double-blind, randomized, placebo-controlled trial.
Tertiary pediatric diabetes clinic.
Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI), with type 1 diabetes.
Metformin (up to 1 g twice a day) or placebo.
Vascular function measured by brachial artery ultrasound [flow-mediated dilatation/glyceryl trinitrate-mediated dilatation (GTN)].
Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45 per group], 10 discontinued intervention, and 1 was lost to follow-up. On metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3 percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or other cardiovascular risk factors. Median (95% CI) adherence, evaluated by electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis.
Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children. These benefits and good safety profile warrant further consideration of its use.
1型糖尿病儿童在动脉粥样硬化之前就存在血管功能障碍。需要早期干预以降低心血管疾病风险。
评估二甲双胍对1型糖尿病儿童血管功能的影响。
为期12个月的双盲、随机、安慰剂对照试验。
三级儿科糖尿病诊所。
90名年龄在8至18岁之间、体重指数（BMI）高于第50百分位数的1型糖尿病儿童。
二甲双胍（每日两次，每次最多1克）或安慰剂。
通过肱动脉超声测量血管功能[血流介导的血管舒张/硝酸甘油介导的血管舒张（GTN）]。
90名参与者入组[41名男孩，年龄13.6（2.5）岁，每组45名]，10人停止干预，1人失访。服用二甲双胍期间，12个月内GTN独立于糖化血红蛋白（HbA1c）改善了3.3个百分点[95%置信区间（CI）0.3，6.3，P = 0.03]，胰岛素剂量降低了0.2 U/kg/d（95% CI 0.1，0.3，P = 0.001），3个月时即有效果。二甲双胍在3个月时对HbA1c有有益影响（P = 0.001），12个月内两组调整后的HbA1c差异为1.0%；95% CI 0.4，1.5（10.9 mmol/mol；95% CI 4.4，16.4），P = 0.001。对颈动脉/主动脉内膜中层厚度、BMI、血脂、血压或其他心血管危险因素无影响。通过电子监测评估，中位（95% CI）依从性为75.5%（65.7，81.5），两组无差异。服用二甲双胍报告的胃肠道副作用更多（发生率比1.65，95% CI 1.08，2.52，P = 0.02），低血糖或糖尿病酮症酸中毒无差异。
二甲双胍改善了1型糖尿病儿童的血管平滑肌功能和HbA1c，并降低了胰岛素剂量。这些益处和良好的安全性值得进一步考虑使用。
