Mechanisms of Type 1 Diabetes Endophenotypes

Study Overview
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Brief Summary
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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.

Official Title
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Mechanisms of Type 1 Diabetes Endophenotypes, by Cluster Analysis

Conditions
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Type 1 Diabetes Mellitus, Genetic Predisposition to Disease

Intervention / Treatment
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* Genetic: Genome sequencing


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>100 patients followed in pediatric diabetology at the university hospital of Geneva: a cohort | Genetic: Genome sequencing<br>* 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.<br>* Other names: Mixed meal tolerance test;|
| Control<br>50 control patients | Genetic: Genome sequencing<br>* 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.<br>* Other names: Mixed meal tolerance test;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes mellitus, Children, Adolescent, Young adult, Genetic, Transcriptomic, Metabolomic, Lipidomic, Genetic risk score