Department of Public Health Solutions, National Institute for Health and Welfare, PO Box 30, FI-00271, Helsinki, Finland.
The Faculty of Social Sciences, University of Tampere, Tampere, Finland.
Diabetologia. 2017 Jul;60(7):1223-1233. doi: 10.1007/s00125-017-4280-9. Epub 2017 May 4.
AIMS/HYPOTHESIS: We investigated the association of early serum fatty acid composition with the risk of type 1 diabetes-associated autoimmunity. Our hypothesis was that fatty acid status during infancy is related to type 1 diabetes-associated autoimmunity and that long-chain n-3 fatty acids, in particular, are associated with decreased risk.
We performed a nested case-control analysis within the Finnish Type 1 Diabetes Prediction and Prevention Study birth cohort, carrying HLA-conferred susceptibility to type 1 diabetes (n = 7782). Serum total fatty acid composition was analysed by gas chromatography in 240 infants with islet autoimmunity and 480 control infants at the age of 3 and 6 months. Islet autoimmunity was defined as repeated positivity for islet cell autoantibodies in combination with at least one of three selected autoantibodies. In addition, a subset of 43 infants with primary insulin autoimmunity (i.e. those with insulin autoantibodies as the first autoantibody with no concomitant other autoantibodies) and a control group (n = 86) were analysed. A third endpoint was primary GAD autoimmunity defined as GAD autoantibody appearing as the first antibody without other concomitant autoantibodies (22 infants with GAD autoimmunity; 42 infants in control group). Conditional logistic regression was applied, considering multiple comparisons by false discovery rate <0.05.
Serum fatty acid composition differed between breastfed and non-breastfed infants, reflecting differences in the fatty acid composition of the milk. Fatty acids were associated with islet autoimmunity (higher serum pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids decreased risk; higher arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Furthermore, fatty acids were associated with primary insulin autoimmunity, these associations being stronger (higher palmitoleic acid, cis-vaccenic, arachidonic, docosapentaenoic and docosahexaenoic acids decreased risk; higher α-linoleic acid and arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Moreover, the quantity of breast milk consumed per day was inversely associated with primary insulin autoimmunity, while the quantity of cow's milk consumed per day was directly associated.
CONCLUSIONS/INTERPRETATION: Fatty acid status may play a role in the development of type 1 diabetes-associated autoimmunity. Fish-derived fatty acids may be protective, particularly during infancy. Furthermore, fatty acids consumed during breastfeeding may provide protection against type 1 diabetes-associated autoimmunity. Further studies are warranted to clarify the independent role of fatty acids in the development of type 1 diabetes.
目的/假设:我们研究了早期血清脂肪酸组成与 1 型糖尿病相关自身免疫的风险之间的关系。我们的假设是,婴儿期的脂肪酸状况与 1 型糖尿病相关自身免疫有关,并且长链 n-3 脂肪酸,特别是,与降低风险有关。
我们在芬兰 1 型糖尿病预测和预防研究的出生队列中进行了嵌套病例对照分析,该队列具有 HLA 赋予的 1 型糖尿病易感性(n=7782)。在 3 个月和 6 个月时,通过气相色谱法分析了 240 名胰岛自身免疫婴儿和 480 名对照婴儿的血清总脂肪酸组成。胰岛自身免疫定义为胰岛细胞自身抗体的重复阳性,同时至少有三种选定的自身抗体之一阳性。此外,还分析了一组 43 名原发性胰岛素自身免疫婴儿(即,作为第一种自身抗体出现的胰岛素自身抗体,没有其他伴随的自身抗体)和对照组(n=86)。第三个终点是原发性 GAD 自身免疫,定义为 GAD 抗体作为第一种抗体出现而没有其他伴随的自身抗体(22 名 GAD 自身免疫患儿;42 名对照组患儿)。应用条件逻辑回归,考虑假发现率 <0.05 的多次比较。
母乳喂养和非母乳喂养婴儿的血清脂肪酸组成不同,反映了乳汁中脂肪酸组成的差异。脂肪酸与胰岛自身免疫有关(较高的血清十五烷酸、棕榈酸、棕榈油酸和二十二碳六烯酸降低风险;较高的花生四烯酸:二十二碳六烯酸和 n-6:n-3 酸比值增加风险)。此外,脂肪酸与原发性胰岛素自身免疫有关,这些关联更强(较高的棕榈油酸、顺式维生素 E、花生四烯酸、二十二碳五烯酸和二十二碳六烯酸降低风险;较高的α-亚麻酸和花生四烯酸:二十二碳六烯酸和 n-6:n-3 酸比值增加风险)。此外,每天摄入的母乳量与原发性胰岛素自身免疫呈负相关,而每天摄入的牛奶量与原发性胰岛素自身免疫呈正相关。
结论/解释:脂肪酸状态可能在 1 型糖尿病相关自身免疫的发展中起作用。鱼类衍生的脂肪酸可能具有保护作用,特别是在婴儿期。此外,母乳喂养期间消耗的脂肪酸可能对 1 型糖尿病相关自身免疫提供保护。需要进一步的研究来阐明脂肪酸在 1 型糖尿病发展中的独立作用。