DataSheet_1_Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity—The TRIGR Nested Case–Control Study.pdf

AimsAltered immune functions as well as fatty acid intake and status have been associated with the development of type 1 diabetes. We aimed to study the relationship between fatty acids and immunological markers in young children with increased genetic risk for type 1 diabetes in order to define putative mechanisms related to development of islet autoimmunity.
MethodsSerum samples for fatty acid and immunological marker measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children born between 2002 and 2007 in 15 countries. Case children (n = 95) were defined as having repeated positivity for at least two out of four diabetes-associated autoantibodies. For each case child, control children were selected matched for country and date of birth (n = 173). Serum fatty acids and immunological markers were measured from cord serum and at the age of 6 and 12 months. Spearman correlation coefficients were calculated between fatty acids and immunological markers.
ResultsCorrelations between circulating fatty acids and immunological markers were different in case children who developed islet autoimmunity than in control children already at birth continuing across the first year of life. In case children, saturated fatty acids (SFAs) showed stronger correlations with immunological markers, while in controls, polyunsaturated fatty acids (PUFAs) showed stronger correlations.
ConclusionsIn cases, SFAs were associated with several immunological markers (CXCL10, IL-6, IL-9, IL-17, and CM-CSF) previously linked to the type 1 diabetes disease process. Findings indicate that fatty acids could have immunomodulatory potential in the early phase of the disease development, although causality between fatty acids and the immunological pathways remains to be explored.
Trial registry numberNCT00179777

【研究目的】免疫功能异常以及脂肪酸摄入与代谢状态均与1型糖尿病（type 1 diabetes）的发生发展密切相关。本研究旨在探究1型糖尿病遗传易感幼儿体内脂肪酸与免疫标志物之间的关联，以明确与胰岛自身免疫（islet autoimmunity）发生相关的潜在机制。

【研究方法】本研究依托降低遗传易感人群胰岛素依赖型糖尿病（Insulin-Dependent Diabetes Mellitus, IDDM）试验（Trial to Reduce IDDM in the Genetically at Risk, TRIGR）的附属研究（Divia），纳入2002年至2007年间来自15个国家的幼儿，采集血清样本用于脂肪酸与免疫标志物检测。病例组儿童（n=95）的判定标准为：四次糖尿病相关自身抗体检测中至少两次呈反复阳性。按照国家与出生日期匹配的原则，为每例病例儿童选取对照儿童（n=173）。分别采集脐带血清以及儿童6月龄、12月龄时的血清样本，检测其中的脂肪酸与免疫标志物水平，并计算脂肪酸与免疫标志物之间的斯皮尔曼相关系数（Spearman correlation coefficients）。

【研究结果】发生胰岛自身免疫的病例组儿童，其循环脂肪酸与免疫标志物的相关性从出生时起即与对照组儿童存在差异，且该差异贯穿出生后第一年。在病例组儿童中，饱和脂肪酸（saturated fatty acids, SFAs）与免疫标志物的相关性更强；而在对照组儿童中，多不饱和脂肪酸（polyunsaturated fatty acids, PUFAs）与免疫标志物的相关性更强。

【研究结论】病例组儿童体内的SFAs与多种此前已被证实与1型糖尿病发病进程相关的免疫标志物（CXCL10、IL-6、IL-9、IL-17及CM-CSF）存在关联。本研究结果提示，脂肪酸在疾病发生的早期阶段可能具备免疫调节潜能，但脂肪酸与免疫通路之间的因果关系仍有待进一步探究。

【试验注册号】NCT00179777