Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)
Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)
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DOI：
10.1007/s00125-003-1033-8
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发表时间：
2003-03-01
期刊：
影响因子：
8.2
通讯作者：
Gale, EAM
中科院分区：
文献类型：
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作者：
Gale, EAM
目的/假说。目的：建立临床试验，以确定烟酰胺是否能预防或延缓I型糖尿病的临床发病。欧洲烟酰胺糖尿病干预试验是一项随机、双盲、安慰剂对照的干预试验，在18个欧洲国家、加拿大和美国进行。入组标准为：1型糖尿病一级家族史，年龄3-40岁，胰岛细胞抗体（ICA）水平大于或等于20 JDF单位，非糖尿病性OGTT；进一步通过静脉葡萄糖耐量试验、GAD抗体、IA-2和胰岛素抗体测定和HLAⅱ类基因分型对研究组进行特征分析。在大约30,000名一级亲属中进行了ICA筛查。共有1004人符合ICA的资格标准，552人（288名男性）被随机分配到治疗组。其中，331人年龄在20岁以下（87%为兄弟姐妹，13%为先证糖尿病患者的后代），221人年龄在20岁及以上（76%为父母，21%为兄弟姐妹，3%为后代）。500例患者口服糖耐量正常，52例（9.4%）出现异常，IV-GTT患者的一期胰岛素反应低于第10百分位（34%）。在354名试验进入者中发现了额外的胰岛自身抗体。在84%的年轻人和80%的老年人中发现了与糖尿病相关的HLA II类单倍型。10%的人群中存在保护性单倍型HLA-DQA1*0102-DQB1*0602。ENDIT已经表明，当有潜在的安全和有效的干预形式可用时，可以在多国合作的基础上进行旨在阻止或延迟I型糖尿病进展的干预试验。生物化学定义的自身抗体的初步筛查将大大减少纳入未来干预试验的低风险个体的数量。
Aims/hypothesis. To set up a clinical trial to establish whether nicotinamide can prevent or delay clinical onset of Type I diabetes.Method. The European Nicotinamide Diabetes Intervention Trial is a randomised, double-blind, placebo-controlled intervention trial undertaken in 18 European countries, Canada and the USA. Entry criteria were a first-degree family history of Type I diabetes, age 3-40 years, confirmed islet cell antibody (ICA) levels greater than or equal to 20 JDF units, and a non-diabetic OGTT; the study group was further characterised by intravenous glucose tolerance testing, measurement of antibodies to GAD, IA-2 and insulin and HLA class II genotyping.Results. ICA screening was carried out in approximately 30,000 first-degree relatives. A total of 1004 individuals fulfilled ICA criteria for eligibility, and 552 (288 male) were randomised to treatment. Of these, 331 were aged less than 20 years (87% siblings and 13% offspring of the proband with diabetes) and 221 were 20 years of age or more (76% parents, 21% siblings and 3% offspring). Oral glucose tolerance was normal in 500 and impaired in 52 (9.4%), and first phase insulin response in the IV-GTT was below the 10(th) centile in 34%. Additional islet autoantibodies were identified in 354 trial entrants. Diabetes-associated HLA class II haplotypes were found in 84% of the younger age group and 80% of the older group. The protective haplotype HLA-DQA1*0102-DQB1*0602 was found in 10% overall.Conclusions/interpretation. ENDIT has shown that a trial of an intervention designed to halt or delay progression to Type I diabetes can be carried out on a multinational collaborative basis, as and when potentially safe and effective forms of intervention become available. Primary screening with biochemically defined autoantibodies will substantially reduce the number of lower risk individuals to be included in future intervention trials.