Theranostics 2017; 7(10):2704-2717. doi:10.7150/thno.19679

Research Paper

Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function

Harinder Singh1✉, Yanbao Yu1, Moo-Jin Suh1, Manolito G Torralba1, Robert D. Stenzel1, Andrey Tovchigrechko1, Vishal Thovarai1, Derek M. Harkins1, Seesandra V. Rajagopala1, Whitney Osborne2, Fran R. Cogen2, Paul B. Kaplowitz2, Karen E. Nelson1, Ramana Madupu1, Rembert Pieper1✉

1. J. Craig Venter Institute, 9714 Medical Center Drive, Rockville, MD 20850;
2. Children's National Health System, 111 Michigan Ave, NW, Washington, DC 20010.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Singh H, Yu Y, Suh MJ, Torralba MG, Stenzel RD, Tovchigrechko A, Thovarai V, Harkins DM, Rajagopala SV, Osborne W, Cogen FR, Kaplowitz PB, Nelson KE, Madupu R, Pieper R. Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function. Theranostics 2017; 7(10):2704-2717. doi:10.7150/thno.19679. Available from

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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.

Keywords: Type 1 Diabetes, Lysosome, Protein network, Gut microbiome, Urinary proteome.