Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes:: a pilot study
Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes:: a pilot study
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DOI：
10.1007/s00125-005-1733-3
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发表时间：
2005-05-01
期刊：
影响因子：
8.2
通讯作者：
Paronen, J
中科院分区：
文献类型：
--
作者：
Åkerblom, HK;Virtanen, SM;Paronen, J
目的/假设：我们的目的是评估在1型糖尿病风险增加的婴儿中进行断奶至水解配方奶粉的饮食干预试验的可行性，并研究干预对儿童早期糖尿病相关自身抗体的影响。方法：我们研究了242名新生儿，他们有一级亲属患有1型糖尿病并携带危险相关的HLA-DQB 1等位基因。在纯母乳喂养后，婴儿进行了一项双盲、随机的试验性试验，试验中使用酪蛋白水解物（Nutramigen;美赞臣约翰逊）或传统的牛奶配方奶粉，直到6-8个月大。在平均4.7年的观察期内，胰岛素，抗谷氨酸脱羧酶和胰岛素瘤相关抗原-2的自身抗体测定放射性结合试验，和胰岛细胞抗体（伊卡）的免疫荧光。结果如下：建立了筛选和鉴定具有HLA赋予的疾病易感性的一级亲属队列，将其纳入饮食干预试验并跟踪其血清转化为自身抗体阳性的可行性。酪蛋白水解物组与对照配方奶粉组相比，自身抗体的累积发生率略低，这表明需要进行更大规模的把握度良好的研究。在调整研究配方喂养的持续时间后，生命表分析显示，干预措施对伊卡（p=0.02）和至少一种自身抗体（p=0.03）的阳性具有显著保护作用。结论/解释：目前的研究提供了有史以来第一个在人类身上的证据，尽管其能力有限，但它可能通过婴儿期的饮食干预来操纵自发的β细胞自身免疫。
Aims/hypothesis: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. Methods: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk- associated HLA-DQB1 alleles. After exclusive breast-feeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. Results: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). Conclusions/interpretation: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.