Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
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DOI：
10.1001/jama.2017.19826
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发表时间：
2018-01-02
影响因子：
120.7
通讯作者：
Wasikowa, Renata
中科院分区：
文献类型：
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作者：
Knip, Mikael;Akerblom, Hans K.;Wasikowa, Renata
重要性早期接触复杂的膳食蛋白质可能会增加遗传性疾病易感儿童患1型糖尿病的风险。有没有完整的蛋白质在广泛水解的formuls.Objective检验假设，断奶广泛水解的公式减少1型糖尿病的累积发病率在幼儿。设计，设置，和参与者一项国际双盲随机临床试验，2159名婴儿与人类白细胞抗原赋予的疾病易感性和第一个-从2002年5月至2007年1月，在15个国家的78个研究中心招募了1081名与1型糖尿病有一定程度亲属关系的婴儿; 1081名被随机分为两组，一组是广泛水解酪蛋白配方奶粉，另一组是常规配方奶粉。参与者的随访于2017年2月28日结束。干预参与者接受酪蛋白水解物或添加20%酪蛋白水解物的传统改良牛奶配方。研究配方暴露的最小持续时间为60天，由6至8个月龄。主要结局和措施主要结局是1型糖尿病诊断根据世界卫生组织的标准。次要结果包括糖尿病诊断时的年龄和安全性（不良事件）。结果在随机分组的2159名新生儿（1021名女性[47.3%]）中，1744名（80.8%）完成了试验。参与者的中位观察时间为11.5年（四分位数[Q] 1-Q3，10.2-12.8）。随机分配至酪蛋白水解物组的患者（n = 91）发生1型糖尿病的绝对风险为8.4%，而随机分配至常规配方奶粉组的患者（n = 82）发生1型糖尿病的绝对风险为7.6%（差异为0.8%[95%CI，-1.6%至3.2%]）。在治疗研究中心作为随机效应时，调整人类白细胞抗原风险组、母乳喂养持续时间、研究配方奶粉食用持续时间、性别和地区后的1型糖尿病风险比为1.1（95% CI，0.8 - 1.5; P = 0.46）。两组诊断1型糖尿病时的中位年龄相似（6.0岁[Q1-Q3，3.1-8.9] vs 5.8岁[Q1-Q3，2.6-9.1];差异为0.2岁[95% CI，-0.9至1.2]）。上呼吸道感染是最常见的不良事件报告（频率，0.48事件/年的水解物组和0.50事件/年的对照组）。结论和相关性在1型糖尿病的风险，断奶到水解配方奶粉与传统配方奶粉相比，并没有减少1型糖尿病的累积发病率后，中位数随访11.5年。这些发现并不支持需要修改1型糖尿病风险婴儿的饮食建议。
IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas.OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children.DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017.INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age.MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events).RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group).CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.