Knip Mikael, Åkerblom Hans K, Becker Dorothy, Dosch Hans-Michael, Dupre John, Fraser William, Howard Neville, Ilonen Jorma, Krischer Jeffrey P, Kordonouri Olga, Lawson Margaret L, Palmer Jerry P, Savilahti Erkki, Vaarala Outi, Virtanen Suvi M
University of Helsinki, Helsinki, Finland.
University of Pittsburgh, Pittsburgh, Pennsylvania.
JAMA. 2014 Jun 11;311(22):2279-87. doi: 10.1001/jama.2014.5610.
The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.
To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-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; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.
The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.
AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).
The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.
Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.
导致临床1型糖尿病的疾病进程通常始于生命的最初几年。早期接触复杂的膳食蛋白质可能会增加有1型糖尿病遗传风险儿童发生β细胞自身免疫的风险。深度水解配方奶粉不含完整蛋白质。
检验这样一种假设，即改用深度水解配方奶粉可降低幼儿糖尿病相关自身抗体的累积发病率。
设计、地点和参与者：一项双盲随机临床试验，于2002年5月至2007年1月在15个国家的78个研究中心招募了2159名具有HLA赋予的疾病易感性且有1型糖尿病一级亲属的婴儿；1078名婴儿被随机分配改用深度水解酪蛋白配方奶粉，1081名婴儿被随机分配改用传统的以牛奶为基础的配方奶粉。对参与者进行观察至2013年4月16日。
参与者分别接受酪蛋白水解物或添加20%酪蛋白水解物的传统牛奶配方奶粉。
主要结局是在分析的4种自身抗体中至少2种与糖尿病相关的自身抗体呈阳性。在中位观察期7.0年（平均6.3年）期间，使用放射结合试验分析胰岛素、谷氨酸脱羧酶和胰岛瘤相关-2（IA-2）分子的自身抗体，并使用免疫荧光法检测胰岛细胞抗体。
随机分配至酪蛋白水解物配方奶粉组（n = 139）中2种或更多胰岛自身抗体呈阳性的绝对风险为13.4%，而随机分配至传统配方奶粉组（n = 117）中为11.4%。与随机分配至传统配方奶粉组相比，随机分配改用酪蛋白水解物配方奶粉组中2种或更多自身抗体呈阳性的未调整风险比为1.21（95%CI，0.94 - 1.54），而在根据HLA风险、母乳喂养持续时间、维生素D使用情况、研究配方奶粉持续时间和摄入量以及地区进行调整后的风险比为1.23（95%CI，0.96 - 1.58）。两组报告的不良事件发生率在临床上无显著差异。
在有1型糖尿病风险的婴儿中，与传统配方奶粉相比，使用水解配方奶粉在7年后并未降低糖尿病相关自身抗体的发生率。这些发现不支持水解配方奶粉有益。试验注册：clinicaltrials.gov标识符：NCT00179777。
