title: Biomarkers of β-Cell Stress and Death in Type 1 Diabetes.
abstract: The hallmark of type 1 diabetes (T1D) is a decline in functional β-cell mass arising as a result of autoimmunity. Immunomodulatory interventions at disease onset have resulted in partial stabilization of β-cell function, but full recovery of insulin secretion has remained elusive. Revised efforts have focused on disease prevention through interventions administered at earlier disease stages. To support this paradigm, there is a parallel effort ongoing to identify circulating biomarkers that have the potential to identify stress and death of the islet β-cells. Whereas no definitive biomarker(s) have been fully validated, several approaches hold promise that T1D can be reliably identified in the pre-symptomatic phase, such that either β-cell preservation or immunomodulatory agents might be employed in at-risk populations. This review summarizes the most promising protein- and nucleic acid-based biomarkers discovered to date and reviews the context in which they have been studied.
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Department of Medicine, Indiana University School of Medicine, I635 Barnhill Drive, MS 2031, Indianapolis, IN, 46202, USA.|Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Indiana Biosciences Research Institute, Indianapolis, IN, 46202, USA.
authors.forename: Raghavendra G
authors.initials: RG
authors.lastname: Mirmira
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Sims
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Farooq
authors.initials: F
authors.lastname: Syed
authors.affiliation: Department of Medicine, Indiana University School of Medicine, I635 Barnhill Drive, MS 2031, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.|Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.|The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.|The Roudebush VA Medical Center, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.
authors.forename: Carmella
authors.initials: C
authors.lastname: Evans-Molina
mesh_terms: D015415:Biomarkers; D002096:C-Peptide / Q000097:blood; D019175:DNA Methylation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D011384:Proinsulin / Q000097:blood; D022661:RNA, Untranslated / Q000097:blood
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D022661:RNA, Untranslated; D011384:Proinsulin
keywords: Biomarkers; Cell-free insulin DNA; Proinsulin; Proinsulin/C-peptide ratio; Type 1 diabetes; Unmethylated insulin DNA; miRNA