Xu, GuanlanThielen, Lance A.Chen, JunqinGrayson, Truman B.Grimes, TiffanyBridges, S. LouisTse, Hubert M.Smith, BlairPatel, RakeshLi, PengEvans-Molina, CarmellaOvalle, FernandoShalev, Anath2021-08-092021-08-092019-10-07Xu, G., Thielen, L. A., Chen, J., Grayson, T. B., Grimes, T., Bridges, S. L., Tse, H. M., Smith, B., Patel, R., Li, P., Evans-Molina, C., Ovalle, F., & Shalev, A. (2019). Serum miR-204 is an early biomarker of type 1 diabetes-associated pancreatic beta-cell loss. American Journal of Physiology-Endocrinology and Metabolism, 317(4), E723–E730. https://doi.org/10.1152/ajpendo.00122.20190193-1849https://hdl.handle.net/1805/26400Pancreatic beta-cell death is a major factor in the pathogenesis of type 1 diabetes (T1D), but straightforward methods to measure beta-cell loss in humans are lacking, underlining the need for novel biomarkers. Using studies in INS-1 cells, human islets, diabetic mice, and serum samples of subjects with T1D at different stages, we have identified serum miR-204 as an early biomarker of T1D-associated beta-cell loss in humans. MiR-204 is a highly enriched microRNA in human beta-cells, and we found that it is released from dying beta-cells and detectable in human serum. We further discovered that serum miR-204 was elevated in children and adults with T1D and in autoantibody-positive at-risk subjects but not in type 2 diabetes or other autoimmune diseases and was inversely correlated with remaining beta-cell function in recent-onset T1D. Thus, serum miR-204 may provide a much needed novel approach to assess early T1D-associated human beta-cell loss even before onset of overt disease.en-USbeta cell deathbiomarkermiR-204T1DArticle