Anhydroglucitol in Children With Type 1 Diabetes

Anhydroglucitol as a Measure of the Functional Beta-cell Mass in Children With Type 1 Diabetes - Pilot Study

The investigators will measure blood levels of 1,5-anhydroglucitol in children with type 1 diabetes and correlate them with parameters related to functional beta-cell mass in diabetic patients. The values will be compared to those obtained in healthy volunteers. Children with newly diagnosed diabetes as well as children with longstanding disease will be included. The aim of the study is to test the validity of 1,5-anhydroglucitol as a novel biomarker of beta-cell mass and function in type 1 diabetes.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: Measurement of blood levels of 1,5-anhydroglucitol

Detailed Description

One-center prospective exploratory pilot study performed in collaboration between the Pediatric Endocrine and Diabetology unit of the University Hospitals of Geneva (HUG) and Prof. Pierre Maechler, Diabetes Center of the Faculty of Medicine, University of Geneva Switzerland.

1,5-anhydroglucitol (1,5-AG), a deoxyhexose present in almost all foods and forming a stable pool in human subjects, has recently been found to be correlated with functional beta-cell mass in two different mouse models of beta-cell dysfunction leading to diabetes. The decline of this biomarker precedes the development of hyperglycemia in lean b-Phb2 -/- and obese db/db diabetic mice, where beta-cell loss occurs through two different mechanisms.

Additional studies have shown a correlation of 1,5-AG levels with risk of progression of type 1 diabetes (T1DM) in auto-antibody positive children, as well as with glycaemic control in patients with type 2 diabetes.

The present project will analyse the correlation between functional beta-cell mass and the circulating levels of 1,5-AG in children with T1DM. This should contribute to the evaluation of a novel biomarker of beta-cell mass and function in T1DM.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Philippe Klee; Phone Number: +41 22 372 45 90; Email: philippe.klee@unige.ch
• Study Contact Backup: Name: Pierre Maechler; Email: pierre.maechler@unige.ch

Study Locations

• Switzerland
  • GE
    • Geneva, GE, Switzerland, 1211
      • Recruiting
      • University Hospital of Geneva
      • Contact: Philippe Klee, MD-PhD; Phone Number: +41 79 55 33 476; Email: philippe.klee@hcuge.ch
      • Principal Investigator: Philippe Klee, MD-PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Among children with type 1 diabetes, aged 2 to 18 years:

15 newly diagnosed patients and 15 age- and sex-matched controls. 5 patients with a diabetes duration of 3 (36 - 47 months), 5 patients with a disease duration of 5 (60 - 71 months) and 5 patients with a disease duration of 10 years (120 - 131 months) and 15 corresponding age- and sex-matched controls.

Description

Inclusion Criteria:

• Type 1 diabetes with positive autoantibodies against islets, insulin, islet antigen 2 (IA2), glutamic acid decarboxylase (GAD) 65 or zinc transporter (ZnT)8.
• Treatment with continuous subcutaneous insulin infusion (CSII) with or without automated insulin delivery (AID).
• Monitoring with a continuous glucose measurement system (CGMS) or flash glucose monitor (FGM).
• Patient willing to keep the same type of CGMS or FGM during the year of observation
• Ability to give informed consent as documented by signature

Exclusion Criteria:

• Patients treated with multiple daily injections (MDI) or not willing to wear a CGMS of FGM
• Patients changing the type of CGMS during the course of the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Newly diagnosed patients with T1DM; The investigators will do prospective measures in 10 to 15 children aged 2 to 18 years, at the time of diagnosis, four months after diagnosis and one year after diagnosis.	Other: Measurement of blood levels of 1,5-anhydroglucitol; Measurement of blood levels of 1,5-anhydroglucitol
Patients with T1DM of different duration; As the functional beta-cell mass gradually declines as disease duration increases, the investigators will do measurements in a cohort of children aged ≤ 18 years, with increasing diabetes duration. The investigators plan to analyze groups of 5 patients with a disease duration of 3 (36 - 47 months), 5 (60 - 71 months) and 10 years (120 - 131 months), respectively.	Other: Measurement of blood levels of 1,5-anhydroglucitol; Measurement of blood levels of 1,5-anhydroglucitol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of 1,5-anhydroglucitol levels in newly diagnosed patients with indirect markers of beta-cell function and mass	Blood levels of 1,5-anhydroglucitol will be correlated with indirect markers of beta-cell function at different moments after diagnosis	Day 1
Correlation of 1,5-anhydroglucitol levels in newly diagnosed patients with indirect markers of beta-cell function and mass	Blood levels of 1,5-anhydroglucitol will be correlated with indirect markers of beta-cell function at different moments after diagnosis	4 months after diagnosis
Correlation of 1,5-anhydroglucitol levels in newly diagnosed patients with indirect markers of beta-cell function and mass	Blood levels of 1,5-anhydroglucitol will be correlated with indirect markers of beta-cell function at different moments after diagnosis	12 months after diagnosis
Correlation of 1,5-anhydroglucitol levels in patients with longstanding disease with indirect markers of beta-cell function and mass	Blood levels of 1,5-anhydroglucitol will be correlated with indirect markers of beta-cell function in patients with different disease duration	In participants with a disease duration of 3 years.
Correlation of 1,5-anhydroglucitol levels in patients with longstanding disease with indirect markers of beta-cell function and mass	Blood levels of 1,5-anhydroglucitol will be correlated with indirect markers of beta-cell function in patients with different disease duration	In participants with a disease duration of 5 years.
Correlation of 1,5-anhydroglucitol levels in patients with longstanding disease with indirect markers of beta-cell function and mass	Blood levels of 1,5-anhydroglucitol will be correlated with indirect markers of beta-cell function in patients with different disease duration	In participants with a disease duration of 10 years.

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Collaborators: University of Geneva, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 26, 2022

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2022-01684

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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