Specificities of Atypical Non AutoImmune Diabetes (ANAID) in the French West Indies

Epidemiological, Clinical, Biological and Genetic Specificities of Atypical Non-AutoImmune Diabetes (ANAID) in the French West Indies

Genetics variants could be involved in atypical non-autoimmune diabetes revealed by ketoacidosis. The objective of this research will be to determine the relationships between the genetic variants already described in known monogenic diabetes or identified as involved in glucose metabolism and its regulation, in insulin signaling pathways or in insulin secretion itself in subjects of African and Indian ancestry with atypical forms of non autoimmune diabetes.

In the French West Indies, the prevalence of diabetes is twice as high as that reported at the national level with a clinical and biological phenotype which seems different, undoubtedly linked to genetic polymorphisms sometimes correlated with specific environmental exposures in these territories. The two most common forms of diabetes are type 1 diabetes (T1D), which accounts for around 5 - 10% of all diabetes, and type 2 diabetes (T2D), which is much more common (around 90 - 95 %). However, in practice, forms of atypical diabetes are described more and more frequently in young subjects, without an autoimmune context, occurring in a family context or not, without the classic phenotype of common type 2 diabetes with the observation in certain populations episodes of ketoacidosis which can be life-threatening. Genetic variants involved in glucose metabolism and its regulation, in insulin signaling pathways, or insulin secretion itself could explain the occurrence of this type of diabetes or episodes of ketoacidosis in these subjects with an evolution towards more or less early insulin withdrawal. The genetic sampling, which is part of the routine etiological diagnosis of these atypical forms, will be carried out with clinical and metabolic evaluation carried out as part of routine care. Unfortunately, this genetic research is not always done systematically. This is a multicenter prospective observational study. This research will be cross-sectional in order to identify in subjects presenting forms of atypical non-autoimmune diabetes (DNAI) found in subjects of African and Indian ancestry in the French West Indies, the presence of known pathogenic mutations described in monogenic diabetes of the MODY type (GCK, HNF1A, HNF4A, PDX1, HNF1B, NEUROD1, CEL, INS, ABCC8, KCNJ11, GATA6, WFS1, TRMT10A, PCBD1, GATA4, APPL1, RFX6, MAFA, SLC19A2, ONECUT1, m.3243A>G, KCNK16) but also new mutations in genes involved in glucose metabolism and its regulation, in insulin signaling pathways, or insulin secretion and this thanks to a molecular screening of the entire exome. A longitudinal follow-up is secondarily planned in order to determine the appearance of complications according to the presence of pathogenic genetic mutations that will have been identified.

Inclusion Criteria:

Phenotypic criteria :

Subjects from Indian or African Ancestry self-declared

Age criteria at diagnosis:

Early onset of diabetes: patient aged between 18 and 47 years at the time of diagnosis of diabetes Clinical criteria: at least 2 criteria Labeled type 2 diabetic

Patient hospitalized for:

Ketoacid decompensation Significant weight loss (more than 10% in less than 6 months) without obvious etiology Lipodystrophic / lipoatrophic appearance Presence of an associated myopathy or deafness Presence of early inaugural nephropathy or within 3 years after diagnosis Presence of early inaugural heart disease or within 3 years after diagnosis Poor response to non-insulin treatments despite good adherence

Biological criteria:

Absent T1D autoantibodies:

Anti-islet antibodies (ICA) Anti-IA2 antibodies Anti-insulin antibodies Anti-ZnT8 antibodies Anti-GAD antibodies

Other criteria:

Informed consent signed by the patient

Exclusion Criteria:

Type 1 diabetes (T1D) Presence of T1D antibodies Secondary diabetes (pancreas diseases, endocrine diseases, drug intake, infection) Other associated autoimmune pathologies Pregnancy Refusal to participate