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?
aged 5-39 years at inclusion;
absence of diabetes meeting the clinical diagnostic American Diabetes Association (ADA) criteria;
persistently positive for one or multiple types of autoantibodies among IAA, GADA, IA-2A and ZnT8A.
Pregnancy or lactation in women; <6 months postpartum
Diabetes meeting the clinical diagnostic ADA criteria;
Use of illicit drugs, or overconsumption of alcohol, or history of drug or alcohol abuse;
Being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders;
Universitair Ziekenhuis Brussel
Lead sponsor
Breakthrough T1D
Collaborator