Established and emerging biomarkers for the prediction of type 1 diabetes: a systematic review

Abstract

Type 1 diabetes (T1D) is an autoimmune disease with a prolonged and variable latent period that culminates in the destruction of pancreatic β-cells and the development of hyperglycemia. There is a need for diagnostic biomarkers to detect more accurately detect individuals with prediabetes to expedite targeting for prevention and intervention strategies. To assess the current ability to predict the insidious development of T1D, we conducted a comprehensive systematic review for established and prospective predictive markers of T1D using the Medline, OVID, and EMBASE databases. Resulting citations were screened for relevance to subject. Our research generated five major categories of markers that are either currently used or forthcoming: genetic, autoantibodies, risk score quantification, cellular immunity, and β-cell function. The current standard used to assess T1D onset or predisposition focuses on autoimmune pathology and disease-associated autoantibodies. Research studies in general go beyond autoantibody screening and assess genetic predisposition, and quantitate risk of developing disease based on additional factors. However, there are few currently used techniques that assess the root of T1D: β-cell destruction. Thus, novel techniques are discussed with the potential to gauge degrees of β-cell stress and failure via protein, RNA, and DNA analyses.

Type 1 Diabetes: Disease Stratification

“…Biomarkers have been correlated with rate of progression ( Fig. 1 ), and used in research studies [26,[29][30][31] , but most have not been validated in longitudinal studies and none have reached a stage where they have become standard of care for informing treatment.…”

“…Several candidate biomarkers (proinsulin/C-peptide ratio, hsp90, noncoding RNAs) for detecting beta cell stress in the periphery are being investigated, and although have not been studied at pre-stage 1 T1D, have been evaluated in later stages of presymptomatic or new onset T1D [29,56,[58][59][60][61] .…”

“…Exhaustion of peripheral blood T cells associated with cellular unresponsiveness and loss of effector function with expression of a T-cell exhaustion signature correlates with clinical remission in several autoimmune diseases [108] and is being evaluated for correlation with both spontaneous remission in presymptomatic T1D and in therapy-induced remission in T1D [109] . Other immune assays are being developed to better predict active disease and rate of progression [29] .…”

Alternate Approaches for Pediatric Type 1 Diabetes Drug Development and Potential Regulatory Approval: A Perspective

“…Currently, 2 years of treatment and/or follow-up in two phase 3 trials is expected by regulatory authorities when submitting a new drug application for drugs to prevent diabetes or to preserve b-cell function (22). However, despite great interest and investigation of alternative markers of b-cell failure, including markers of b-cell stress (29), currently no other valid potential primary outcome measures (particularly short-term measures) have been identified. Moreover, combinations of immunomodulatory agents are likely necessary to achieve complete clinical responses.…”

Association investigation of BACH2 rs3757247 and SOD2 rs4880 polymorphisms with the type 1 diabetes and diabetes long-term complications risk in the Polish population

“…Type 1 diabetes (DM1) is a multifactorial disease that results from autoimmune destruction of β-cells in the pancreas (1). DM1 characterises the largest range of concordance rates in monozygotic twins among all autoimmune diseases, and this provides convincing evidence that genetic factors are strongly involved in the pathogenesis of DM1 (2).…”