Role of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes

Summary

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.

Eligibility

Inclusion Criteria:

* 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 first degree relatives from at least 2 generations
* 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

Exclusion Criteria:

* 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)
* Patient with known secondary diabetes (i.e. endocrine disorders such as Cushing syndrome, pancreatectomy, drug-induced diabetes)
* Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol,
* Individuals under legal protection (sauvegarde de justice).

Conditions2

Browse More Trials