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. 2024 Sep;48(5):949-959.
doi: 10.4093/dmj.2023.0166. Epub 2024 Mar 22.

A New Tool to Identify Pediatric Patients with Atypical Diabetes Associated with Gene Polymorphisms

Sophie Welsch  1 , Antoine Harvengt  1 , Paola Gallo  2 , Manon Martin  3 , Dominique Beckers  4 , Thierry Mouraux  4 , Nicole Seret  5 , Marie-Christine Lebrethon  6 , Raphaël Helaers  7 , Pascal Brouillard  7 , Miikka Vikkula  7 , Philippe A Lysy  1   2
Affiliations

A New Tool to Identify Pediatric Patients with Atypical Diabetes Associated with Gene Polymorphisms

Sophie Welsch et al. Diabetes Metab J. 2024 Sep.

Abstract

Backgruound: Recent diabetes subclassifications have improved the differentiation between patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus despite several overlapping features, yet without considering genetic forms of diabetes. We sought to facilitate the identification of monogenic diabetes by creating a new tool that we validated in a pediatric maturity-onset diabetes of the young (MODY) cohort.

Methods: We first created the DIAgnose MOnogenic DIAbetes (DIAMODIA) criteria based on the pre-existing, but incomplete, MODY calculator. This new score is composed of four strong and five weak criteria, with patients having to display at least one weak and one strong criterion.

Results: The effectiveness of the DIAMODIA criteria was evaluated in two patient cohorts, the first consisting of patients with confirmed MODY diabetes (n=34) and the second of patients with T1DM (n=390). These DIAMODIA criteria successfully detected 100% of MODY patients. Multiple correspondence analysis performed on the MODY and T1DM cohorts enabled us to differentiate MODY patients from T1DM. The three most relevant variables to distinguish a MODY from T1DM profile were: lower insulin-dose adjusted A1c score ≤9, glycemic target-adjusted A1c score ≤4.5, and absence of three anti-islet cell autoantibodies.

Conclusion: We validated the DIAMODIA criteria, as it effectively identified all monogenic diabetes patients (MODY cohort) and succeeded to differentiate T1DM from MODY patients. The creation of this new and effective tool is likely to facilitate the characterization and therapeutic management of patients with atypical diabetes, and promptly referring them for genetic testing which would markedly improve clinical care and counseling, as well.

Keywords: Diabetes mellitus; Diabetes mellitus, type 1; Diabetes mellitus, type 2; Genetic testing; Pediatrics.

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Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.
Multiple correspondence analysis (MCA) of DIAgnose MOnogenic DIAbetes (DIAMODIA) variables between the maturity-onset diabetes of the young (MODY) and type 1 diabetes mellitus (T1DM) cohorts.
Fig. 2.
Fig. 2.
Univariate logistic regression between DIAgnose MOnogenic DIAbetes (DIAMODIA) variables of maturity-onset diabetes of the young and type 1 diabetes mellitus cohorts. IDAA1c, insulin-dose adjusted A1c; GTAA1c, glycemic target-adjusted A1c; aab, autoantibody; IA2, islet cell antigen 2; GAD65, glutamate decarboxylase 65.
Fig. 3.
Fig. 3.
Random Forest ranks variables of the DIAgnose MOnogenic DIAbetes (DIAMODIA) criteria according to their importance in distinguishing type 1 diabetes mellitus profile from maturity-onset diabetes of the young profile. IDAA1c, insulin-dose adjusted A1c; GTAA1c, glycemic target-adjusted A1c; aab, autoantibody; GAD65, glutamate decarboxylase 65; IA2, islet cell antigen 2.
None
See this image and copyright information in PMC

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Supplementary concepts