Circulating biomarkers during progression to type 1 diabetes: A systematic review.

Aim: Progression to type 1 diabetes (T1D) is defined in stages and clinical disease is preceded by a period of silent autoimmunity. Improved prediction of the risk and rate of progression to T1D is needed to reduce the prevalence of diabetic ketoacidosis at presentation as well as for staging participants for clinical trials. This systematic review evaluates novel circulating biomarkers associated with future progression to T1D. Methods: PubMed, Ovid, and EBSCO databases were used to identify a comprehensive list of articles. The eligibility criteria included observational studies that evaluated the usefulness of circulating markers in predicting T1D progression in at-risk subjects <20 years old. Results: Twenty-six studies were identified, seventeen were cohort studies and ten were case control studies. From the 26 studies, 5 found evidence for protein and lipid dysregulation, 11 identified molecular markers while 12 reported on changes in immune parameters during progression to T1D. An increased risk of T1D progression was associated with the presence of altered gene expression, immune markers including regulatory T cell dysfunction and higher short-lived effector CD8+ T cells in progressors. Discussion: Several circulating biomarkers are dysregulated before T1D diagnosis and may be useful in predicting either the risk or rate of progression to T1D. Further studies are required to validate these biomarkers and assess their predictive accuracy before translation into broader use. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42020166830).