Nutritional Primary Prevention of Type 1 Diabetes

该项目的总体目标是确定至少在生命的前6个月内断奶服用酪蛋白水解物(NutraMicen TM)是否能降低遗传易感儿童的1型糖尿病发病率。具体目的1-a：确定在具有风险相关的人类白细胞抗原基因和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自身抗体的频率。I-b：确定，在风险相关的人类白细胞抗原(HLA)基因携带者和受影响的一级亲属中，停用酪蛋白水解物是否能降低临床糖尿病的发生率。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这种疾病，并且人类白细胞抗原基因分型显示受试者属于风险增加组)将被邀请参加研究。将进行一项国际性、多中心、双盲、随机、对照的2种不同营养补充剂试验。新生儿将被随机分配到母乳喂养后，在至少生命的前6个月(干预期)接受2个配方奶粉中的1个。测试配方将是酪蛋白水解物，不含完整的牛奶蛋白。酪蛋白水解物对NOD小鼠无促糖尿病作用。控制配方将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，受试者将被跟踪6年和10年，在此期间测量血清标志物并记录糖尿病的发展。为了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、加拿大和其他15个国家进行，为期两年。参与这项随机营养预防研究的受试者估计数量约为2800人。这需要对大约6200名新生儿进行基因筛查。这一研究问题具有重要的公共卫生影响。

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.