Identification and Characterization of Monogenic Diabetes (DIAGENE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Assistance Publique - Hôpitaux de Paris
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris Identifier:
First received: October 27, 2011
Last updated: June 1, 2015
Last verified: May 2015
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.

Condition Intervention
Other: Constitution of a biological bank
Other: Metabolic studies

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Identification and Genetic, Clinical and Metabolic Characterization of Monogenic Forms of Insulin-dependent Diabetes

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Identification and genetic, clinical and metabolic characterization of monogenic diabetes forms [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    to identify genes responsible for monogenic insulin-dependant diabetes, and to define and characterize the corresponding genetic diabetes entities with respect to the genetic and molecular defect, clinical and phenotypic features and biochemistry

Secondary Outcome Measures:
  • Diagnosis of monogenic diabetes [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    to diagnose these monogenic diabetes entities and to evaluate the proportion of insulin-dependant diabetes which are explained by monogenic determinism, depending on several parameters, such as familial structure and clinical characteristics.

  • Clinical and biological characterization of total or partial deficiency of the genes responsible for monogenic diabetes [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To characterize precisely the clinical and biological consequences of total or partial deficiency of the genes responsible for monogenic diabetes, and explore their possible role in glucidic metabolism. This way suggest them as candidate genes for common forms of diabetes.

Estimated Enrollment: 1000
Study Start Date: September 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Gene identification and phenotyping
Identification of patients (probands), questionnaire and informed consent of patients and their families, biological sampling, DNA and RNA extraction, genetic study for gene identification, re-contact of family members and relatives (with consent) for metabolic study of mutation carriers, and complementary studies of homozygous patients in some cases
Other: Constitution of a biological bank
Blood samples for the constitution of a biobank (DNA, RNA, serum)
Other: Metabolic studies
oral glucose tolerance test (OGTT) intravenous glucose tolerance test (IVGTT) hyperglycemic clamp staged glucose perfusion arginine test measure of body composition (BIPHOTONIC absorptiometry, DEXA)

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.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01481623

Contact: Pierre-Jean Guillausseau, MD +33 (0)1 49 95 63 80
Contact: Cécile Julier, PhD +33 (0)1 57 27 85 43

Lariboisiere hospital Recruiting
Paris, France, 75010
Principal Investigator: Pierre-Jean Guillausseau         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Study Director: Pierre-Jean Guillausseau, MD CHU Lariboisière, AP-HP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01481623     History of Changes
Other Study ID Numbers: P081230
Study First Received: October 27, 2011
Last Updated: June 1, 2015
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
metabolism processed this record on November 24, 2015