Mechanisms of Type 1 Diabetes Endophenotypes (METYDIA)

Mechanisms of Type 1 Diabetes Endophenotypes, by Cluster Analysis

The goal of this observational study consists of performing cluster analysis to decipher underlying disease mechanisms of type 1 diabetes in children and young adults.

To this end, we will combine clinical, laboratory, genetic, transcriptomic, and metabolomic datasets of an extensively phenotyped cohort of children and young adults with type 1 diabetes. We will also assess the risk for cardiovascular diseases in this most vulnerable diabetes cohort.

Study Overview

• Status: Recruiting
• Conditions: Genetic Predisposition to Disease; Type 1 Diabetes Mellitus
• Intervention / Treatment: Genetic: Genome sequencing

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Valerie VS Schwitzgebel, MD; Phone Number: +41 22 372 45 90; Email: valerie.schwitzgebel@unige.ch
• Study Contact Backup: Name: Fanny FL Iafrate-Luterbacher, MD; Phone Number: +41 78 603 06 92; Email: fanny.luterbacher@hcuge.ch

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Recruiting
    • University Hospital of Geneva
    • Contact: Valerie VS Schwitzgebel, MD; Phone Number: +41 22 372 45 90; Email: valerie.schwitzgebel@unige.ch
    • Contact: Fanny FL Iafrate Luterbacher, MD; Phone Number: +41 78 603 06 92; Email: fanny.luterbacher@hcuge.ch
    • Principal Investigator: Valerie VS Schwitzgebel, MD
    • Sub-Investigator: Fanny FL Iafrate Luterbacher, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 25 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children, adolescents, and young adults followed at the pediatric diabetology unit of the University Hospital of Geneva.

Controls Children, adolescents, and young adults coming for a routine blood sample at University Hospital of Geneva

Description

Inclusion Criteria (Type 1 Diabetic patients):

• Informed consent as documented by signature
• Patient's age: between 0 and 25 years old.
• Children, adolescents, and young adult patients followed in diabetology.

Exclusion Criteria (Type 1 Diabetic patients):

• No exclusion criteria

Inclusion Criteria (Controls):

• Informed consent as documented by signature
• Patient's age: 25 less than 6 years of age and 25 between 6 and 25 years old.
• Healthy patient

Exclusion Criteria (Controls):

• Patient receiving treatment affecting metabolic control (ex: systemic corticoids, beta blocker, immunotherapy etc.)
• Concomitant disease that may affect the analysis of the results (ex: cancer, active autoimmune disease requiring treatment)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; 100 patients followed in pediatric diabetology at the university hospital of Geneva: a cohort	Genetic: Genome sequencing; 100 extensively phenotyped pediatric and young adult patients for genotyping, metabolomic and lipidomic analyses. Polygenic risk scores for type 1 diabetes and cardiovascular disease will be performed. For patients older than 6 years who agree to do a second visit (optional), a Mixed Meal Tolerance Test (MMTT: the gold standard for assessing beta cell function) will be done as well as transcriptomic analysis.; Other Names: Metabolomic; Transcriptomic; Lipidomic; Mixed meal tolerance test
Control; 50 control patients	Genetic: Genome sequencing; 100 extensively phenotyped pediatric and young adult patients for genotyping, metabolomic and lipidomic analyses. Polygenic risk scores for type 1 diabetes and cardiovascular disease will be performed. For patients older than 6 years who agree to do a second visit (optional), a Mixed Meal Tolerance Test (MMTT: the gold standard for assessing beta cell function) will be done as well as transcriptomic analysis.; Other Names: Metabolomic; Transcriptomic; Lipidomic; Mixed meal tolerance test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cluster analysis to decipher underlying mechanisms of type 1 diabetes	We will combine clinical, laboratory, genetic, transcriptomic, and metabolomic datasets of an extensively phenotyped cohort of type 1 diabetes patients (Children and young adults). We will create clinical and genetic correlates with the following clinical parameters: Age at diabetes onset (years), disease duration (years), BMI (kg/m2), diabetes autoantibodies, C-peptide level (pmol/l) and decline over time, HbA1c (%), insulin dose (U/kg/d), ketoacidosis at disease onset (y/n), lipid levels (Total cholesterol, triglycerides, HLD, LDL, Lipoprotein(a)), macro- and microvascular complications, ethnicity, family history for diabetes, associated autoimmune diseases (e.g., autoimmune thyroiditis or celiac disease) and mixed meal tolerance test.	blood sampling and analyses

Collaborators and Investigators

• Sponsor: Pediatric Clinical Research Platform
• Collaborators: University Hospital, Geneva; University of Geneva, Switzerland
• Investigators: Principal Investigator: Valerie VS Schwitzgebel, MD, University Hospital of Geneva / University of Geneva

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Adolescent; Genetic; Children; Young adult; Metabolomic; Type 1 diabetes mellitus; Genetic risk score; Transcriptomic; Lipidomic
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Disease Attributes; Diabetes Mellitus; Diabetes Mellitus, Type 1; Disease Susceptibility; Genetic Predisposition to Disease
• Other Study ID Numbers: 2022-02119

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