Abstract
Background: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies. Methods: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment. Results: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation. Conclusions: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.
| Original language | English (US) |
|---|---|
| Article number | 66 |
| Journal | Communications Medicine |
| Volume | 4 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2024 |
Funding
We thank Krister Aronsson and Maria Bjorklund from Lund University for assistance with database searches and Russell de Souza from McMaster University for advice on critical appraisal. The ADA/EASD Precision Diabetes Medicine Initiative, within which this work was conducted, has received the following support: The Covidence license was funded by Lund University (Sweden) for which technical support was provided by Maria Bj\u00F6rklund and Krister Aronsson (Faculty of Medicine Library, Lund University, Sweden) and Russell de Souza from McMaster University for advice on critical appraisal. Administrative support was provided by Lund University (Malm\u00F6, Sweden), University of Chicago (IL, USA), and the American Diabetes Association (Washington D.C., USA). The Novo Nordisk Foundation (Hellerup, Denmark) provided grant support for in-person writing group meetings (PI: L Phillipson, University of Chicago, IL). J.L.F.: DiabDocs K12 program 1K12DK133995-01 (DiMeglio, Maahs PIs), The Leona M. & Harry B. Helmsley Charitable Trust Grant #2307-06126 (Felton PI); M.J.R.: NIH NIDDK R01DK124395; R.A.O.: R.A.O. had a UK MRC confidence in concept award to develop a type 1 diabetes GRS biochip with Randox R&D and has ongoing research funding from Randox; and has research funding from a Diabetes UK Harry Keen Fellowship (16/0005529), National Institute of Diabetes and Digestive and Kidney Diseases grants (NIH R01 DK121843\u201301 and U01DK127382\u201301), JDRF (3-SRA-2019\u2013827-S-B, 2-SRA-2022\u20131261-S-B, 2-SRA-2002\u20131259-S-B, 3-SRA-2022\u20131241-S-B, and 2-SRA-2022\u20131258-M-B), and The Larry M and Leona B Helmsley Charitable Trust; and is supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the National Institutes for Health Research or the Department of Health and Social Care; S.A.L.: NIH NIAID R01 AI141952 (PI), NIH NCI R01 CA231226 (Other support), NIH NIAID 1 R01HL149676 (Other support), NIH NIDDK 1UC4DK117483 (subaward), JDRF 3-SRA-2019-851-M-B; S.O.G.: NIH R01 DK121843\u201301; S.R.: R01 DK122586, The Leona M and Harry B Helmsley Charitable Trust 2204-05134; C.E.M.: R01DK093954, R01DK127236, U01DK127786, R01DK127308, and UC4DK104166, U54DK118638, P30 P30 DK097512), a US Department of Veterans Affairs Merit Award (I01BX001733), grants from the JDRF (3-IND-2022-1235-I-X) and Helmsley Charitable Trust (2207-05392), and gifts from the Sigma Beta Sorority, the Ball Brothers Foundation, and the George and Frances Ball Foundation; L.A.D.: NIH for TrialNet U01DK106993/6163-1082-00-BO, DiabDocs K12 program 1K12DK133995-01, CTSI UL1TR001108-01; H.I.: K23DK129799; R.J.: NIH R03-DK127472 and The Leona M. and Harry B. Helmsley Charitable Trust (2103-05094); J.W.: JDRF 2-SRA-2022-1282-M-X, 3-SRA-2022-1095-M-B, 4-SRA-2022-1246-M-N, 3-SRA-2023-1374-M-N; K.G.: The Leona M. and Harry B. Helmsley Charitable Trust and Sanford Health. E.K.S.: R01DK121843; R01DK121929A1, R01DK133881, U01DK127786, U01 DK127382 Effort from this grant (to E.K.S., H.I., J.F.) is also supported by Grant 2021258 from the Doris Duke Charitable Foundation through the COVID-19 Fund to Retain Clinical Scientists collaborative grant program and was made possible through the support of Grant 62288 from the John Templeton Foundation.
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Internal Medicine
- Epidemiology
- Medicine (miscellaneous)
- Assessment and Diagnosis
