Nutritional Primary Prevention of Type 1 Diabetes

该项目的总体目标是确定至少在出生后的前6个月停用酪蛋白水解物（Nutramigen TM）是否能降低遗传易感儿童1型糖尿病的发病率。特定目的I-a：确定断奶酪蛋白水解物是否能降低具有风险相关HLA基因型和一级亲属为1型糖尿病患者的糖尿病预测自身抗体的频率。I-b：目的是确定断奶使用酪蛋白水解物是否能降低HLA基因型相关患者和受影响的一级亲属的临床糖尿病发病率。将邀请遗传风险增加的新生儿和患有1型糖尿病的一级亲属（母亲、父亲或兄弟姐妹患有该疾病，HLA基因分型显示受试者属于风险增加组）参加研究。一项国际、多中心、双盲、随机对照试验将对两种不同的营养补充剂进行研究。新生儿将被随机分配，在母乳喂养后至少在生命的前6个月（干预期）接受2种配方奶粉中的1种。测试配方将是酪蛋白水解物，不含完整的牛奶蛋白。酪蛋白水解物在NOD小鼠中不会致糖尿病。对照配方类似于常用的以牛奶为基础的婴儿配方。在干预期间和干预后对受试者进行为期6年和10年的随访，在此期间测量血清学指标并记录糖尿病的发展情况。这样的临床试验是必要的，以得到一个明确的答案的假设。招聘在美国、加拿大和其他15个国家进行，为期2年。参与随机营养预防研究的受试者估计约有2800人。这需要对大约6200名新生儿进行基因筛查。该研究问题具有重要的公共卫生意义。

The overall objective of the project is to determine whether weaning to a casein hydrolysate (Nutramigen TM) during at least the first 6 months of life reduces the incidence of Type 1 diabetes in genetically susceptible children. Specific Aims I-a: To determine, if weaning to casein hydrolysate reduces the frequency of diabetes-predictive autoantibodies in subjects with risk-associated HLA genotype and a first degree relative with type 1 diabetes. I-b: To determine, if weaning to casein hydrolysate reduces the frequency of clinical diabetes in subjects with risk-associated HLA genotype and an affected first degree relative. Newborn infants, who have increased genetic risk and first degree relatives with type 1 diabetes (mother, father or sibling has the disease, and HLA genotyping shows the subject to belong to the increased risk group) will be invited for the study. An international, multicenter, double blind, randomized, controlled trial of 2 different nutritional supplements will be performed. The newborn infants will be randomly allocated to receive after breast feeding 1 of 2 formulas during at least the first 6 months of life (the intervention period). The test formula will be a casein hydrolysate, free of intact cows milk proteins. The casein hydrolysate is not diabetogenic in the NOD mouse. The control formula will be similar to a commonly used cow milk based infant formula. Subjects will be followed during and after the intervention period for 6 and 10 years time during which serological markers are measured and the development of diabetes will be recorded. Such a clinical trial is necessary to get a definite answer to the hypothesis. Recruitment is carried out during a 2-year period in the U.S., Canada and 15 other countries. The estimated number of subjects participating in the randomized nutritional prevention study is approximately 2,800. This requires that genetic screening would be performed in approximately 6,200 newborn infants. The study question has important public health implications.