LAUSR

Type 1 diabetes (T1D) is characterized by the loss of insulin-producing beta-cells. We currently lack diagnostic tools to measure T1D progression. Using systematic approaches involving unprejudiced discovery analyses in human tissues and clinical samples, we identify microRNAs that are: i) associated with insulin expression during embryonic development (N>60); ii) predictive of and necessary for insulin transcription (N=698); and iii) dysregulated in individuals with (vs. without) T1D (N=200). Insulin cfDNA (assessed by ddPCR) and microRNA (assessed by TaqMan qPCR) biomarkers were measured in around; i) N=400 Australian T1D individuals; ii) N=30 longitudinal samples from children at risk of T1D; iii) N=100 clinical trial samples from individuals receiving IFN-a or Exenatide vs. placebo; iv) N=400 Hong Kong Chinese individuals with T1D; v) N=700 Danish individuals at diagnosis of T1D and vi) N=400 Asian Indian T1D subjects. Among N=600 Australian samples, we identified miRNAs (N=5) that were significantly increased in the circulation of T1D individuals (vs. controls), decreased (at least 2 Fold Change/FC, P Disclosure M. Joglekar: None. R. Farr: None. W. Wong: None. K. Rother: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. C.S. Yajnik: None. R.C. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd.. M.E. Craig: None. T. Jones: None. A. Hardikar: None.