• 纳入2159名糖尿病易感新生儿(具有易感基因或一级亲属有1型糖尿病史),随机分为酪蛋白水解配方奶粉组和传统奶粉组,并至少服用60天;
  • 中位随访时间11.5年,酪蛋白水解组1型糖尿病发病率8.4%,而传统组7.6%,没有统计学差异;
  • 两组发病时间中位数分别为6岁、5.8岁,无统计学差异;
  • 上呼吸道感染是报道的最常见的不良反应,但两组发生率没有差异;
  • 暂无证据表明断奶后采用水解配方奶粉喂养可以降低1型糖尿病的风险。
JAMA [IF:51.273]

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial



2018-01-02, Article

Abstract & Authors:展开

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.

First Authors:
Writing Group for the TRIGR Study Group

Correspondence Authors:
Mikael Knip

All Authors:
Writing Group for the TRIGR Study Group,Mikael Knip