Clinical trial NCT01481623: Identification and Characterization of Monogenic Diabetes
Official title: Identification and Genetic, Clinical and Metabolic Characterization of Monogenic Forms of Insulin-dependent Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes
Keywords: Diabetes
neonatal
consanguinity
monogenic
metabolism
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2011-11-29
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Type 1 Diabetes is a multifactorial disease, with a strong genetic contribution of HLA genes, and minor contributions of many additional genes. The investigators hypothesis is that in addition to multifactorial inheritance, there are subtypes of diabetes that are caused by defects in single genes (monogenic diabetes). The aim of this project is to identify these genes, based on detailed clinical and characterization of patients, and to describe the corresponding genetic diabetes entities with respect to the genetic and molecular defect, clinical features and biochemistry. Based on the investigators study design, most of these diabetes entities will be caused by mutations affecting the two copies of the corresponding gene. In addition, the investigators will study the relatives of the patients, and explore if carriers of these genetic defects (i.e. only one copy of the gene being defective) may have a predisposition to common forms of diabetes, mainly type 2 diabetes.

Detailed description: In the first phase of the study the investigators will recruit patients and families, with a strong bias for "extreme" forms of diabetes (very early onset and/or syndromic diabetes) and familial context suggestive of monogenic inheritance (e.g. consanguinity, multiplicity of diabetic siblings) and perform genetic studies on these to identify the genes. After obtaining informed consent, the investigators will collect clinical information on diabetes and other associated diseases and features, family information on diabetes, and collect blood samples for DNA, RNA, serum and cell lines. The investigators will then perform genetic studies to identify the genes responsible for these monogenic forms of diabetes.

After identification of genes, the second phase of the study will be to test the consequence of carrier status for the identified mutations on metabolic traits related to glucose metabolism. For this, after obtaining informed consent, the investigators will extend the recruitment of the initial families (after gene identification) to recruit relatives who may be carriers of these mutations. The investigators will determine the carrier status of these subjects and perform a detailed clinical description as well as metabolic studies to evaluate their glucose metabolism.

This study will lead to the identification of new monogenic diabetes entities, and their corresponding genes, and may also result in the identification of new genes predisposing to common forms of diabetes. This project has implication for diagnosis of these monogenic forms of diabetes, and may result in some cases in improved care for the patients, including prevention and treatment.

Eligibility criteria: Inclusion Criteria:

* First phase: to have an "extreme" form of diabetes, based on clinical, phenotypic and familial criteria. Parents and siblings of the proband will be sampled.
* Second phase: (after gene identification): to be a relative of the proband, potential carrier of the mutation

Exclusion Criteria:

* Non consent to participate to the study

Primary outcomes:
measure: Identification and genetic, clinical and metabolic characterization of monogenic diabetes forms
timeFrame: 36 months
Secondary outcomes:
measure: Diagnosis of monogenic diabetes
timeFrame: 36 months
measure: Clinical and biological characterization of total or partial deficiency of the genes responsible for monogenic diabetes
timeFrame: 36 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Lariboisiere hospital
Study officials:
affiliation: CHU Lariboisière, AP-HP
name: Pierre-Jean Guillausseau, MD
role: STUDY_DIRECTOR
References: