Abstract
Background: Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field. Methods: Pubmed and Embase databases were searched (1990-2022) using inclusion/exclusion criteria for studies that sequenced one or more monogenic diabetes genes in at least 100 probands (Question 1), evaluated a non-obsolete genetic testing method to diagnose monogenic diabetes (Question 2). The risk of bias was assessed using the revised QUADAS-2 tool. Existing guidelines were summarized for questions 3-5, and review of studies for questions 6-7, supplemented by expert recommendations. Results were summarized in tables and informed recommendations for clinical practice. Results: There are 100, 32, 36, and 14 studies included for questions 1, 2, 6, and 7 respectively. On this basis, four recommendations for who to test and five on how to test for monogenic diabetes are provided. Existing guidelines for variant curation and gene-disease validity curation are summarized. Reporting by gene names is recommended as an alternative to the term MODY. Key steps after making a genetic diagnosis and major gaps in our current knowledge are highlighted. Conclusions: We provide a synthesis of current evidence and expert opinion on how to use precision diagnostics to identify individuals with monogenic diabetes.
| Original language | English (US) |
|---|---|
| Article number | 136 |
| Journal | Communications Medicine |
| Volume | 3 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Funding
The ADA/EASD Precision Diabetes Medicine Initiative (PMDI), 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). 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). S.M. has a personal award from Wellcome Trust Career Development scheme (223024/Z/21/Z) and holds Institutional funds from the NIHR Biomedical Research Centre Funding Scheme. P.R.N. was supported by grants from the European Research Council (AdG #293574), Stiftelsen Trond Mohn Foundation (Mohn Center of Diabetes Precision Medicine), the University of Bergen, Haukeland University Hospital, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund \u201CPersonalised Medicine for Children and Adults\u201D), and the Novo Nordisk Foundation (grant #54741). J.M.I. was supported by a grant from the National Institute of Health (K08DK133676). S.E.F. is supported by a Wellcome Trust Senior Research Fellowship (Grant Number 223187/Z/21/Z). ALG is a Wellcome Trust Senior Fellow (200837/Z/16/Z) and is also supported by NIDDK (UM-1DK126185). EDF is a Diabetes UK RD Lawrence Fellow (19/005971). KRO is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. R.M. has received honoraria for consulting or educational activities for Eli Lilly, Novo Nordisk and Boeringer Ingelheim. S.M. has Investigator initiated funding from DexCom and serves on the Board of Trustees for the Diabetes Research & Wellness Foundation (UK). LK Billings: Received honoraria for consulting activities for Novo Nordisk, Bayer, Lilly, Xeris, and Sanofi which are unrelated to this present work. ALG\u2019s spouse holds stock options in Roche and is an employee of Genentech. No other authors have competing interests. S.M. has a personal award from Wellcome Trust Career Development scheme (223024/Z/21/Z) and holds Institutional funds from the NIHR Biomedical Research Centre Funding Scheme. P.R.N. was supported by grants from the European Research Council (AdG #293574), Stiftelsen Trond Mohn Foundation (Mohn Center of Diabetes Precision Medicine), the University of Bergen, Haukeland University Hospital, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund \u201CPersonalised Medicine for Children and Adults\u201D), and the Novo Nordisk Foundation (grant #54741). J.M.I. was supported by a grant from the National Institute of Health (K08DK133676). S.E.F. is supported by a Wellcome Trust Senior Research Fellowship (Grant Number 223187/Z/21/Z). ALG is a Wellcome Trust Senior Fellow (200837/Z/16/Z) and is also supported by NIDDK (UM-1DK126185). EDF is a Diabetes UK RD Lawrence Fellow (19/005971). KRO is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Internal Medicine
- Epidemiology
- Medicine (miscellaneous)
- Assessment and Diagnosis
