While insulin replacement therapy restores the health and prevents the onset of diabetic complications (DC) for many decades, some T1D patients have elevated hemoglobin A1c values suggesting poor glycemic control, a risk factor of DC. We surveyed the stool microbiome and urinary proteome of a cohort of 220 adolescents and children, half of which had lived with T1D for an average of 7 years and half of which were healthy siblings. Phylogenetic analysis of the 16S rRNA gene did not reveal significant differences in gut microbial alpha-diversity comparing the two cohorts. The urinary proteome of T1D patients revealed increased abundances of several lysosomal proteins that correlated with elevated HbA1c values. In silico protein network analysis linked such proteins to extracellular matrix components and the glycoprotein LRG1. LRG1 is a prominent inflammation and neovascularization biomarker. We hypothesize that these changes implicate aberrant glycation of macromolecules that alter lysosomal function and metabolism in renal tubular epithelial cells, cells that line part of the upper urinary tract.

中文翻译：

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1型糖尿病：尿蛋白质组学和蛋白质网络分析支持溶酶体功能的扰动

尽管胰岛素替代疗法可恢复健康并防止糖尿病并发症（DC）发作数十年，但一些T1D患者的血红蛋白A1c值升高，表明血糖控制不良，这是DC的危险因素。我们调查了220名青少年和儿童的粪便微生物组和尿蛋白质组，其中一半患有T1D的平均寿命为7年，其中一半是健康的兄弟姐妹。16S rRNA基因的系统发育分析没有显示两个小组相比肠道微生物α-多样性的显着差异。T1D患者的尿蛋白质组显示与HbA1c值升高相关的几种溶酶体蛋白的丰度增加。在计算机上蛋白质网络分析将此类蛋白质与细胞外基质成分和糖蛋白LRG1关联起来。LRG1是一个突出的炎症和新血管形成生物标志物。我们假设这些变化暗示大分子糖基化异常，改变了肾小管上皮细胞（排在上尿路一部分的细胞）的溶酶体功能和代谢。