Hydrolyzed Infant Formula and Early β-Cell Autoimmunity A Randomized Clinical Trial
Hydrolyzed Infant Formula and Early β-Cell Autoimmunity A Randomized Clinical Trial
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DOI：
10.1001/jama.2014.5610
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发表时间：
2014-06-11
影响因子：
120.7
通讯作者：
Virtanen, Suvi M.
中科院分区：
文献类型：
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作者：
Knip, Mikael;Akerblom, Hans K.;Virtanen, Suvi M.
重要性导致临床1型糖尿病的疾病过程通常始于生命的头几年。早期接触复杂的饮食蛋白质可能会增加1型糖尿病遗传风险儿童的β细胞自身免疫风险。广泛水解性配方奶粉不含完整的蛋白质。目的验证广泛水解性配方奶粉可降低幼儿糖尿病相关自身抗体累积发病率的假设。设计、背景和参与者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名患有人类白细胞抗原-1型糖尿病易感性且有一级亲属的婴儿参加了一项双盲随机临床试验，其中1078人被随机分成断奶组，1081人被随机分成两组，分别以常规牛奶配方奶粉断奶。参与者被观察到2013年4月16日。干预措施参与者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。MAIN结果和测量在分析的4个糖尿病相关自身抗体中，至少有2个初步结果为阳性。用放射结合试验和免疫荧光法分析胰岛素、谷氨酸脱羧酶和胰岛素瘤相关2(IA-2)分子的自身抗体，中位观察期为7.0年(平均6.3年)。结果在随机服用酪蛋白水解物配方的患者(n=139)中，2种或2种以上的胰岛自身抗体阳性的绝对风险为13.4%，而随机使用传统配方的患者(n=117)的绝对阳性风险为11.4%。在随机接受酪蛋白水解物脱机的患者中，2种或2种以上自身抗体阳性的未调整风险比为1.21(95%CI，0.94~1.54)，而调整后的风险比为1.23(95%CI，0.96~1.58)，而调整后的风险比为1.23(95%CI，0.96~1.58)。两组报告的不良事件发生率在临床上没有显著差异。结论在有1型糖尿病风险的婴儿中，与传统配方奶粉相比，使用水解型配方奶粉并不能降低7年后糖尿病相关自身抗体的发生率。这些发现并不支持从水解型奶粉中获益。
IMPORTANCE 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 beta-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.OBJECTIVE 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.INTERVENTIONS The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.MAIN OUTCOMES 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).RESULTS 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% Cl, 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% Cl, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.CONCLUSIONS AND RELEVANCE 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.