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个月内断奶使用酪蛋白水解物（Nutramigen TM）是否会降低遗传易感儿童的1型糖尿病发病率。具体目标I-a：确定在具有风险相关HLA基因型和1型糖尿病一级亲属的受试者中，停用酪蛋白水解物是否能降低糖尿病预测性自身抗体的频率。I-b：为了确定，如果断乳酪蛋白水解物降低风险相关的HLA基因型和受影响的一级亲属的受试者的临床糖尿病的频率。将邀请遗传风险增加的新生儿和1型糖尿病一级亲属（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。将对2种不同的营养补充剂进行国际、多中心、双盲、随机、对照试验。新生儿将被随机分配，在出生后至少6个月（干预期）内接受2种配方奶粉中的1种。试验配方为酪蛋白水解产物，不含完整的牛奶蛋白。酪蛋白水解产物在NOD小鼠中不具有致糖尿病性。对照配方食品将类似于常用的基于牛乳的婴儿配方食品。将在干预期间和之后对受试者进行6年和10年的随访，在此期间测量血清学标志物并记录糖尿病的发展。要想对这一假设得到明确的答案，这样的临床试验是必要的。招聘在美国进行，为期2年，加拿大和其他15个国家。估计参与随机营养预防研究的受试者人数约为2，800人。这需要对大约6 200名新生儿进行基因筛查。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.