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
Pregnant or breastfeeding woman,
Any contraindication to the study exams including known allergies or contraindication to contrasts for the scan
Patient with known monogenic diabetes (defined as identification of class 4 and 5 variants according to ACMG)
First or second-degree relatives with monogenic diabetes established by molecular genetics (class 4 and 5 variants according to ACMG)
Parallel
WGS coupled with MCM
Diagnostic testWhole genome will be screened and analysis will focus on pathogenic and likely pathogenic variants. The list of variants of interest will be recorded until examination and discussion during the MCM. MCM will edit a final synthesis concerning the pathogenicity of identified variants.
Number of patients with one or several genetic alterations likely causal of diabetes
Number of patients in each group with one or several genetic alterations likely causal of diabetes
Number of patients with an impact on treatment modification
Number of patients in each group with an impact on treatment modification including discontinuation and reason of this modification
Number of genetic alterations likely causal of diabetes
Number of genetic alterations likely causal of diabetes (classified as class 4 or 5 variants)
Feasibility of the whole genome sequencing (WGS) coupled with multidisciplinary conciliation meeting (MCM) on diagnosis of atypical forms of diabetes: time to access to the genetic data
time between blood sampling and availability of genetic data by GLUCOGEN laboratories
Feasibility of the WGS coupled with MCM on diagnosis of atypical forms of diabetes: time between blood sampling and MCM
time between blood sampling and MCM
Number and characteristics of new genomic variations responsible for diabetes development
Number and characteristics of new genomic variations responsible for diabetes development
Number and characteristics of genomic variations and their association with defined phenotypes including integrated diagnostic biomarkers
Number and characteristics of genomic variations and their association with defined phenotypes including integrated diagnostic biomarkers
Number and characteristics of genomic variations known as drug targets
Number and characteristics of genomic variations known as drug targets
Number and characteristics of genomic variations of metabolism, transport or drug targets of diabetes and their consequences on treatment response
Number and characteristics of genomic variations of metabolism, transport or drug targets of diabetes and their consequences on treatment response
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Institut National de la Santé Et de la Recherche Médicale, France
Lead sponsor
Commissariat A L'energie Atomique
Collaborator
Rennes University Hospital
Collaborator
Central Hospital, Nancy, France
Collaborator
Nantes University Hospital
Collaborator
Imagine Institute
Collaborator
APHP
Collaborator
Hospices Civils de Lyon
Collaborator
Université Lumière Lyon 2
Collaborator
University Hospital, Toulouse
Collaborator
