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ACE抑制剂和他汀类药物用于1型糖尿病青少年患者
ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes


M. Loredana Marcovecchio ... 糖尿病 妇产科和儿科 • 2017.11.02
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• 1型糖尿病治疗指南更新

儿童青少年1型糖尿病慢性并发症宜早预警早干预

 

梁雁,罗小平*

华中科技大学同济医学院附属同济医院儿科

*通讯作者

 

世界范围内1型糖尿病(type 1 diabetes,T1DM)发病率以每年2%~5%的速度增长,其中儿童青少年尤其5岁以下儿童增长显著1。2017年国际糖尿病联盟(IDF)全球糖尿病地图(第八版)显示,中国儿童青少年T1DM患病例数位居全球第四。

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摘要


背景

在1型糖尿病青少年患者中,如青春期期间的白蛋白排泄迅速增加,之后出现微量白蛋白尿和大量白蛋白尿的风险升高,而微量白蛋白尿和大量白蛋白尿是肾脏和心血管病的远期危险因素。我们假设白蛋白排泄水平高的青少年可能受益于血管紧张素转换酶(ACE)抑制剂和他汀类药物。尚未有人在青少年中对这些药物进行过充分评估。

 

方法

我们对4,407名年龄在10~16岁的1型糖尿病青少年患者进行了筛选,并确定了白蛋白与肌酐比值(ACR)处于该人群前1/3的1,287人;443人被纳入一项对一种ACE抑制剂和一种他汀类药物开展的安慰剂对照试验,随机分组,使用2×2析因设计,以尽可能减小年龄、性别和糖尿病持续时间等基线特征的差异。两种药物干预的主要结局都是白蛋白排泄的变化:在随访的第2~4年每6个月一次连续3个清晨收集尿样,计算ACR,借此评估白蛋白排泄的变化并将其表示为曲线下面积。关键性次要结局包括微量白蛋白尿的产生、视网膜病变的进展、肾小球滤过率的变化、血脂水平以及心血管风险指标(颈动脉内膜中层厚度以及超敏C反应蛋白和不对称二甲基精氨酸水平)。

 

结果

ACE抑制剂治疗、他汀治疗或两者联用对主要结局都没有影响。与使用安慰剂相比,使用ACE抑制剂时微量白蛋白尿发生率较低;考虑到结果为阴性的主要结局和统计分析计划,这种较低的发生率并不显著(风险比0.57;95%置信区间[CI],0.35~0.94)。他汀的使用使总胆固醇水平、低密度脂蛋白胆固醇水平和非高密度脂蛋白胆固醇水平显著降低,甘油三酯水平和载脂蛋白B与载脂蛋白A1比值也显著降低,而两种药物对颈动脉内膜中层厚度等其他心血管标志物、肾小球滤过率或视网膜病变进展均无显著效应。药物治疗方案的总体依从率为75%,各组间的严重不良事件相当。

 

结论

使用一种ACE抑制剂和一种他汀类药物并未使ACR随时间出现改变(由青少年糖尿病研究基金会[Juvenile Diabetes Research Foundation]等资助;AdDIT在ClinicalTrials.gov的编号为NCT01581476)。





作者信息

M. Loredana Marcovecchio, M.D., Scott T. Chiesa, Ph.D., Simon Bond, Ph.D., Denis Daneman, M.D., Sarah Dawson, M.Sc., Kim C. Donaghue, M.D., Timothy W. Jones, M.D., Farid H. Mahmud, M.D., Sally M. Marshall, M.D., H. Andrew W. Neil, D.Sc., R. Neil Dalton, Ph.D., John Deanfield, M.D., and David B. Dunger, M.D. for the AdDIT Study Group*
From the Department of Paediatrics (M.L.M., D.B.D.) and the Wellcome Trust–Medical Research Council Institute of Metabolic Science (D.B.D.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital (S.B., S.D.), Cambridge, the National Centre for Cardiovascular Prevention and Outcomes, University College London (S.T.C., J.D.), and the WellChild Laboratory, Evelina London Children’s Hospital, St. Thomas’ Hospital (R.N.D.), London, the Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne (S.M.M.), and the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford (H.A.W.N.) — all in the United Kingdom; the Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto (D.D., F.H.M.); and the Institute of Endocrinology and Diabetes, Children’s Hospital at Westmead and University of Sydney, Sydney (K.C.D.), and the Telethon Kids Institute, University of Western Australia, Perth (T.W.J.) — both in Australia. Address reprint requests to Dr. Dunger at the University of Cambridge, Department of Paediatrics, Box 116, Level 8, Cambridge Biomedical Campus, Cambridge CB2 0QQ, United Kingdom, or at dbd25@cam.ac.uk. *A complete list of investigators in the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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