Multiple environmental triggers have been proposed to explain the increased incidence of type 1 diabetes (T1D). These include viral infections, microbiome disturbances, metabolic disorders, and vitamin D deficiency. Here, we used ELISA to examine blood plasma from juvenile T1D subjects and age-matched controls for the abundance of several circulating factors relevant to these hypotheses. We screened plasma for sCD14, mannose binding lectin (MBL), lipopolysaccharide binding protein (LBP), c-reactive protein (CRP), fatty acid binding protein 2 (FABP2), human growth hormone, leptin, total adiponectin, high molecular weight (HMW) adiponectin, total IgG, total IgA, total IgM, endotoxin core antibodies (EndoCAbs), 25(OH) vitamin D, vitamin D binding protein, IL-7, IL-10, IFN-γ, TNF-α, IL-17A, IL-18, and IL-18BPa. Subjects also were tested for prevalence of antibodies targeting adenovirus, parainfluenza 1/2/3, Coxsackievirus, cytomegalovirus, Epstein-Barr virus viral capsid antigen (EBV VCA), herpes simplex virus 1, and Saccharomyces cerevisiae. Finally, all subjects were screened for presence and abundance of autoantibodies targeting islet cell cytoplasmic proteins (ICA), glutamate decarboxylase 2 (GAD65), zinc transporter 8 (ZNT8), insulinoma antigen 2 (IA-2), tissue transglutaminase, and thyroid peroxidase, while β cell function was gauged by measuring c-peptide levels. We observed few differences between control and T1D subjects. Of these, we found elevated sCD14, IL-18BPa, and FABP2, and reduced total IgM. Female T1D subjects were notably elevated in CRP levels compared to control, while males were similar. T1D subjects also had significantly lower prevalence of EBV VCA antibodies compared to control. Lastly, we observed that c-peptide levels were significantly correlated with leptin levels among controls, but this relationship was not significant among T1D subjects. Alternatively, adiponectin levels were significantly correlated with c-peptide levels among T1D subjects, while controls showed no relationship between these two factors. Among T1D subjects, the highest c-peptide levels were associated with the lowest adiponectin levels, an indication of insulin resistance. In total, from our examination we found limited data that strongly support any of the hypotheses investigated. Rather, we observed an indication of unexplained monocyte/macrophage activation in T1D subjects judging from elevated levels of sCD14 and IL-18BPa. These observations were partnered with unique associations between adipokines and c-peptide levels among T1D subjects.

已提出多种环境诱因来解释1型糖尿病（T1D）发病率的增加。这些包括病毒感染，微生物组紊乱，代谢紊乱和维生素D缺乏症。在这里，我们使用ELISA检查了来自青少年T1D受试者和年龄匹配的对照组的血浆中与这些假设相关的几种循环因子的含量。我们筛选了血浆中的sCD14，甘露糖结合凝集素（MBL），脂多糖结合蛋白（LBP），c反应蛋白（CRP），脂肪酸结合蛋白2（FABP2），人类生长激素，瘦素，总脂联素，高分子量（ HMW）脂联素，总IgG，总IgA，总IgM，内毒素核心抗体（EndoCAbs），25（OH）维生素D，维生素D结合蛋白，IL-7，IL-10，IFN-γ，TNF-α，IL- 17A，IL-18和IL-18BPa。酿酒酵母。最后，对所有受试者进行针对胰岛细胞胞浆蛋白（ICA），谷氨酸脱羧酶2（GAD65），锌转运蛋白8（ZNT8），胰岛素瘤抗原2（IA-2），组织转谷氨酰胺酶和甲状腺过氧化物酶的自身抗体的筛选。 ，而β细胞功能则通过测量c肽水平来衡量。我们观察到对照和T1D受试者之间几乎没有差异。其中，我们发现sCD14，IL-18BPa和FABP2升高，总IgM降低。与对照组相比，女性T1D受试者的CRP水平显着升高，而男性相似。与对照组相比，T1D受试者的EBV VCA抗体患病率也明显较低。最后，我们观察到对照组中c肽水平与瘦素水平显着相关，但在T1D受试者中这种关系并不显着。或者，在T1D受试者中，脂联素水平与c肽水平显着相关，而对照显示这两个因素之间没有关系。在T1D受试者中，最高的c肽水平与最低的脂联素水平相关，这表明胰岛素抵抗。总体而言，通过我们的检查，我们发现有限的数据强有力地支持了所研究的任何假设。相反，我们从sCD14和IL-18BPa水平升高的情况下观察到了T1D受试者无法解释的单核细胞/巨噬细胞激活的迹象。这些观察结果与T1D受试者中脂肪因子和c肽水平之间的独特关联相关。最高的c肽水平与最低的脂联素水平相关，这表明胰岛素抵抗。总体而言，通过我们的检查，我们发现有限的数据强有力地支持了所研究的任何假设。相反，我们从sCD14和IL-18BPa水平升高的情况下观察到了T1D受试者无法解释的单核细胞/巨噬细胞激活的迹象。这些观察结果与T1D受试者中脂肪因子和c肽水平之间的独特关联相关。最高的c肽水平与最低的脂联素水平相关，这表明胰岛素抵抗。总体而言，通过我们的检查，我们发现有限的数据强有力地支持了所研究的任何假设。相反，我们从sCD14和IL-18BPa水平升高的情况下观察到了T1D受试者无法解释的单核细胞/巨噬细胞激活的迹象。这些观察结果与T1D受试者中脂肪因子和c肽水平之间的独特关联相关。