Continuous Monitoring of Glycemic Variability to Predict Dys- and Hyperglycemia in Asymptomatic Type 1 Diabetes

Summary

The goal of this longitudinal clinical trial is to measure variability of interstitial glucose levels with a user-friendly real-time continuous glucose monitoring (CGM) technology at regular intervals in normo- and dysglycemic multiple autoantibody-positive individuals (age 5-39 years), in comparison with single autoantibody-positive individuals in the same age range. Participants will asked to undergo repeated oral glucose tolerance tests (OGTTs) (age 5-39 years) and hyperglycemic clamp tests (age 12-39 years) in parallel for a period of at least 2-3 years. In case of confirmed dysglycemia, we propose to perform CGM and OGTT every 3 months.

The main questions the study aims to answer are:

1. Do the amplitude and time trends of CGM-derived glycemic variability indices and OGTT- and clamp-derived variables differ between the intermediate, high and very high risk groups?
2. Can (changes in) CGM-derived glycemic variability indices predict/detect dysglycemia in initially normoglycemic (single or multiple autoantibody-positive) individuals with the same diagnostic efficiency as OGTT- or clamp-derived variables?
3. Can (changes in) CGM-derived glycemic variability indices predict clinical onset in (stage 1 or 2) multiple autoantibody-positive individuals with the same diagnostic efficiency as OGTT- or clamp-derived variables?
4. Can correlating (changes in) CGM-derived indices with (changes in) OGTT- and clamp-derived variables help to better understand the sequence of events leading to dysglycemia and clinical onset, as well as the relative contribution of beta cell function and insulin action to glycemic variability according to disease stage and biological and phenotypical characteristics of the individuals?

Conditions

• Type1 Diabetes Mellitus

Interventions

DIAGNOSTIC_TEST

Oral glucose tolerance test (OGTT)

Longitudinal study using repeated OGTT, CGM and hyperglycemic clamp tests to evaluate glycemic variability, beta cell function and insulin action in individuals at moderate, high and very high risk of clinical onset of type 1 diabetes. OGTT is performed every 6 months (every 3 months in case of dysglycemia) in all participants.

DIAGNOSTIC_TEST

Hyperglycemic clamp test

Longitudinal study using repeated OGTT, CGM and hyperglycemic clamp tests to evaluate glycemic variability, beta cell function and insulin action in individuals at moderate, high and very high risk of clinical onset of type 1 diabetes. Clamp test is performed every 12 months in single autoantibody-positive participants and every 6 months in multiple autoantibody-positive participants. Clamp tests are not performed in participants aged between 5-11 years.

DIAGNOSTIC_TEST

Continuous glucose monitoring

Longitudinal study using repeated OGTT, CGM and hyperglycemic clamp tests to evaluate glycemic variability, beta cell function and insulin action in individuals at moderate, high and very high risk of clinical onset of type 1 diabetes. A 10-day CGM recording is performed every 6 months (every 3 months in case of dysglycemia) in all participants.

Sponsors & Collaborators

• Breakthrough T1D

  collaborator OTHER

• Universitair Ziekenhuis Brussel

  lead OTHER

Principal Investigators

• Bart Keymeulen · Vrije Universiteit Brussel

Study Design

Allocation

NA

Purpose

SCREENING

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

5 Years

Max Age

39 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-08-09

Primary Completion

2026-04-30

Completion

2028-08-31

Countries

• Belgium

Study Locations