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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Glucose Metabolism Disorders; Metabolic Diseases; Genetic Variation; Diabetes Mellitus (Type 2); Genetic Profile

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 118

Contacts and Locations

• Study Contact: Name: Fritz-Line VELAYOUDOM, Doctor; Phone Number: 0590 89 13 00; Email: fritz-line.velayoudom@chu-guadeloupe.fr

Study Locations

• Guadeloupe
  • Guadeloupe
    • Les Abymes, Guadeloupe, Guadeloupe, 97159
      • Centre Hospitalier Universitaire de la Guadeloupe
      • Contact: Eunice NUBRET; Phone Number: 0590934686; Email: eunice.nubret@chu-guadeloupe.fr
      • Contact: Fritz-Line VELAYOUDOM, Doctor; Phone Number: 0590934686; Email: fritz-line@chu-guadeloupe.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

subjects of African and Indian ancestry with atypical forms of non autoimmune diabetes.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
case; subjects of African and Indian ancestry with atypical forms of non autoimmune diabetes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
known pathogenic mutations described in monogenic diabetes of the MODY type	pourcentage	At inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
new pathogenic mutations identified in genes involved in glucose metabolism and its regulation,	pourcentage	At inclusion
genetic mutations.	présence/absence	At inclusion
association between clinical and biological data and DNAI	odds ration	At inclusion
comparing the genetic data found in African and Indian ancestry population	Results with a significant p-value (p < 0.05)	At inclusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de la Guadeloupe
• Investigators: Principal Investigator: Fritz-Line VELAYOUDOM, Doctor, CHU de la Guadeloupe

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ketoacidosis; Monogenic diabetes; Exome sequencing; Afro-Caribbean; Genetic diagnosis; Pathogenic variant; African and Indian ancestry
• Additional Relevant MeSH Terms: Endocrine System Diseases; Diabetes Mellitus; Acid-Base Imbalance; Acidosis; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Metabolic Diseases; Glucose Metabolism Disorders; Ketosis
• Other Study ID Numbers: PAP_RIPH2_2025/09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No