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. 2023 Oct 5;3(1):136.
doi: 10.1038/s43856-023-00369-8.

The use of precision diagnostics for monogenic diabetes: a systematic review and expert opinion

Rinki Murphy #  1   2 , Kevin Colclough #  3 , Toni I Pollin #  4 , Jennifer M Ikle  5   6 , Pernille Svalastoga  7   8 , Kristin A Maloney  4 , Cécile Saint-Martin  9 , Janne Molnes  8   10 ; ADA/EASD PMDI; Shivani Misra  11   12 , Ingvild Aukrust  8   10 , Elisa de Franco  13 , Sarah E Flanagan  13 , Pål R Njølstad  7   8 , Liana K Billings  14   15 , Katharine R Owen  16   17 , Anna L Gloyn  18   19   20
Collaborators, Affiliations

The use of precision diagnostics for monogenic diabetes: a systematic review and expert opinion

Rinki Murphy et al. Commun Med (Lond). .

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.

Plain language summary

Some diabetes types, called monogenic diabetes, are caused by changes in a single gene. It is important to know who has this kind of diabetes because treatment can differ from that of other types of diabetes. Some treatments also work better than others for specific types, and some people can for example change from insulin injections to tablets. In addition, relatives can be offered a test to see if they are at risk. Genetic testing is needed to diagnose monogenic diabetes but is expensive, so it’s not possible to test every person with diabetes for it. We evaluated published research on who should be tested and what test to use. Based on this, we provide recommendations for doctors and health care providers on how to implement genetic testing for monogenic diabetes.

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Conflict of interest statement

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’s spouse holds stock options in Roche and is an employee of Genentech. No other authors have competing interests.

Figures

Fig. 1
Fig. 1. Critical appraisal of evidence using the Joanna Briggs Institute (JBI) Critical Appraisal tool for Systematic Reviews.
A Results for papers from question 1. B Results for papers from question 2. The horizontal axis for the heatmap refer to questions 1–10 of the 10-item JBI checklist. Green is Yes, Red is No, Gray is unclear. Non-applicable answers were left blank. A completes list of papers in (A, B) can be found in Supplementary Data 1 and 2.
Fig. 2
Fig. 2. Schematic overview of how precision diagnostics leads to precision treatment and precision prognostics.
Examples of genetic forms of diabetes identified through precision diagnostics and how these lead to precision treatment and prognostics. Current gaps and challenges identified through the systematic review are highlighted.
See this image and copyright information in PMC

References

    1. Gloyn AL, Drucker DJ. Precision medicine in the management of type 2 diabetes. Lancet Diabetes Endocrinol. 2018;6:891–900. doi: 10.1016/S2213-8587(18)30052-4. - DOI - PubMed
    1. International Diabetes Federation IDF Diabetes eAtlas (International Diabetes Federation, 2022).
    1. Bowman P, et al. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. Lancet Diabetes Endocrinol. 2018;6:637–646. doi: 10.1016/S2213-8587(18)30106-2. - DOI - PMC - PubMed
    1. Pearson ER, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N. Engl. J. Med. 2006;355:467–477. doi: 10.1056/NEJMoa061759. - DOI - PubMed
    1. Pearson ER, et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003;362:1275–1281. doi: 10.1016/S0140-6736(03)14571-0. - DOI - PubMed