Role of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes
The main objective of the study is to assess the contribution of whole genome sequencing (WGS) coupled with a multidisciplinary conciliation meeting (MCM) on diagnosis of atypical forms of diabetes compared to an in-silico analysis of a panel of validated genes (ISApanel), corresponding to current practice, in a randomized trial. Notably, the questions it aims to answer are: * The feasibility of the WGS coupled with MCM on diagnosis of atypical forms of diabetes, * The contribution of WGS coupled with MCM on number of genetic alterations likely causal of diabetes identified and with a modification in care and support of patients. After inclusion and sampling for genotyping, patients will be followed for 5 years. The target population is 1020 adults with atypical diabetes for whom it is possible to obtain a blood sample.
• Subjects ≥18 years with confirmed diabetes mellitus according to WHO criteria (World Health Organization: Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF Consultation. Geneva, World Health Org., 2006.)
• Age ≤ 45 years at diabetes diagnosis
• Body mass index ≤ 35 kg/m² at diabetes diagnosis
• Negative results of specific antibodies determination (GAD65, IA2, ZnT8) until the inclusion visit
• Presenting atypical diabetes defined by at least one of the following:
• Exocrine pancreatic disease
• Familial history: diabetes diagnosed in a parent, child or sibling
• Notion of familial consanguinity
• Syndromic clinical features (dysmorphy, developmental delay, mental retardation…) or unusual abnormalities/features that are not part of diabetic complications or co-morbidities;
• Early occurrence of microvascular complications (≤ 5 years after diabetes diagnosis)
• Major insulinopenia at diagnosis (C peptide \< 0.2 nmol/L and/or documented ketosis)
• Patient who conserved endogenous insulin secretion (positive C peptide value) but a need for insulin therapy initiation during the first year following diagnosis due to therapeutic failure of well conducted therapeutic intensification
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Patient with a social security number in compliance with the French law (dispositions relatives aux recherches impliquant la personne humaine prévues aux articles L 1121-1 et suivants du Code de la Santé Publique)
• Signed and dated informed consent form