RecruitingNot ApplicableNCT05777330

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

Sponsor

Universitair Ziekenhuis Brussel

Enrollment

75 participants

Start Date

Aug 9, 2023

Study Type

INTERVENTIONAL

Conditions

Type1 Diabetes Mellitus

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?

Eligibility

Min Age: 5 YearsMax Age: 39 Years

Inclusion Criteria3

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.

Exclusion Criteria8

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;
Treatment with immune modulating or diabetogenic medication (e.g. corticosteroids) or medication that act to lower glycemia (oral antidiabetics) or agents that may influence insulin sensitivity or secretion;
Gastric bypass or banding;
History of acute or chronic pancreatitis, or (partial) pancreatectomy
History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the subjects.

Interventions

DIAGNOSTIC_TESTOral 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_TESTHyperglycemic 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_TESTContinuous 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.