Diabetes mellitus; Diabetes mellitus, type 1; Diabetes mellitus, type 2; Genetic testing; Pediatrics; Glycated Hemoglobin; Insulin; Humans; Child; Male; Female; Adolescent; Polymorphism, Genetic; Child, Preschool; Diagnosis, Differential; Glycated Hemoglobin/analysis; Cohort Studies; Diabetes Mellitus, Type 2/genetics; Diabetes Mellitus, Type 2/diagnosis; Diabetes Mellitus, Type 1/genetics; Diabetes Mellitus, Type 1/diagnosis; Endocrinology, Diabetes and Metabolism
Abstract :
[en] [en] 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.
Disciplines :
Pediatrics Endocrinology, metabolism & nutrition
Author, co-author :
Welsch, Sophie ; Pediatrics Unit, Institute for Experimental and Clinical Research, UCLouvain, Brussels, Belgium
Harvengt, Antoine; Pediatrics Unit, Institute for Experimental and Clinical Research, UCLouvain, Brussels, Belgium
Gallo, Paola; Pediatric Endocrinology Unit, Saint-Luc University Clinics, Brussels, Belgium
Martin, Manon; Louvain Institute of Biomolecular Science and Technology (IBST) Unit, UCLouvain, Brussels, Belgium
Beckers, Dominique; Pediatric Endocrinology and Diabetology Unit, CHU-UCL Namur sites Saint-Elisabeth and Mont-Godinne, Namur, Belgium
Mouraux, Thierry; Pediatric Endocrinology and Diabetology Unit, CHU-UCL Namur sites Saint-Elisabeth and Mont-Godinne, Namur, Belgium
Seret, Nicole; Pediatric Endocrinology and Diabetology Unit, Clinique CHC MontLégia (CHC MontLégia Clinic), Liège, Belgium
Helaers, Raphaël; Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
Brouillard, Pascal; Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
Vikkula, Miikka; Human Molecular Genetics, de Duve Institute, UCLouvain, Brussels, Belgium
Lysy, Philippe A ; Pediatrics Unit, Institute for Experimental and Clinical Research, UCLouvain, Brussels, Belgium ; Pediatric Endocrinology Unit, Saint-Luc University Clinics, Brussels, Belgium
Language :
English
Title :
A New Tool to Identify Pediatric Patients with Atypical Diabetes Associated with Gene Polymorphisms.
Fondation Saint Luc F.R.S.-FNRS - Fonds de la Recherche Scientifique Innoviris - Institut Bruxellois pour la Recherche et l'Innovation UC Louvain UCL Saint-Luc - Cliniques Universitaires Saint-Luc
Funding text :
This research was supported by clinical research funds from the Fondation Saint-Luc (FSL), the Fonds de la Recherche Scientifique (FNRS), Innoviris and Action de Recherche Concert\u00E9e (ARC). The work was supported by Innoviris, UCLouvain (Action de Recherche Concert\u00E9e; ARC), Cliniques Universitaires Saint-Luc (Fonds de Recherche Clinique) and by the Fondation Saint-Luc (mandate and Bourse \u2018Prof. Martin Buysschaert\u2019). We thank the team of pediatric nurses from the general pediatric service of the Cliniques Universitaires Saint-Luc. Our center is a Reference center and part of the Endo-ERN rare diabetes study group.This research was supported by clinical research funds from the Fondation Saint-Luc (FSL), the Fonds de la Recherche Sci-entifique (FNRS), Innoviris and Action de Recherche Concer-t\u00E9e (ARC).
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