Longitudinal Study of the GLUcagon REsponse to Hypoglycemia in Children and Adolescents With New-onset Type 1 DIAbetes

NCT06770621 | Recruiting

• 1 other identifier: 2022/02FEV/043
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

The GLUREDIA study investigates the counter-regulatory response (CRR) during hypoglycemia in children with type 1 diabetes (T1D). Hypoglycemia can lead to severe symptoms, but is normally counteracted by CRR, corresponding to the secretion of hormones to maintain normoglycemia. Hypoglycemia is common in T1DM but some patients develop severe hypoglycemia as a result of CRR dysfunction. Despite several studies in adults, the presence of CRR dysfunction remains unpredictable and not well understood. The objective of GLUREDIA is therefore to describe and predict the evolution of CRR in children with T1DM.

Conditions

Severe Hypoglycemia; Type1diabetes

Keywords

Pediatric; Hypoglycemia; Diabetes

Outcome Measures

Primary Outcomes (2)

• To investigate the evolution of pancreatic α-cell function. (WP1)

  Regular clinical and biological monitoring will be performed during this period as well as four insulin-induced hypoglycemia (IIH) tests.

  18 months per patient

• To evaluate the presence of blood biomarkers that correlate with the evolution of α-cell function. (WP1)

  Regular clinical and biological monitoring will be performed during this period as well as four insulin-induced hypoglycemia (IIH) tests. Hormones and other blood parameters will be measured and genome, proteome and microRNA (miRs) analysis will be performed during the IIH tests and during the biological follow-up. The expected results are the description and prediction of CRR in the first months after T1DM.

  18 months per patient

Secondary Outcomes (6)

• Conduct an assessment of the management of severe hypoglycemia. (WP2)

  Baseline

• Evaluate the α-cell function in first-degree relatives of patients with type 1 diabetes. (WP3)

  Baseline

• Characterize the glycemic profile and α-cell function. (WP4)

  Baseline

• Evaluate the phenomenon of counter-regulation in patients with proven growth hormone. (WP5)

  Baseline

• Study the link between the clinical characteristics of diabetic patients and their genome (WP6)

  Baseline

Study Arms (7)

To investigate the evolution of pancreatic α-cell function. (WP1)

EXPERIMENTAL

Regular clinical and biological monitoring will be conducted during this period, as well as four insulin-induced hypoglycemia (IIH) tests. Hormones and other blood parameters will be measured, and an analysis of the genome, proteome, and micro-RNAs (miRs) will be performed during these IIH tests and throughout the biological monitoring. The primary goal of this study is to find a correlation between the patient's phenotype and the various biological results obtained, mainly blood biomarkers, in order to subsequently determine models to predict the state of pancreatic α-cell function in the first months post-diagnosis.

Diagnostic Test: Insulin-induced hypoglycemia test

Conduct an assessment of the management of severe hypoglycemia. (WP2)

ACTIVE COMPARATOR

Study of glycemic variations collected by the continuous glucose monitoring sensor in the days preceding a severe hypoglycemia. The aim of this analysis is to identify a specific glycemic profile in patients in the days leading up to severe hypoglycemia in order to better anticipate such events.

Other: Observation-questionnaire

Evaluate the α-cell function in first-degree relatives of patients with type 1 diabetes. (WP3)

EXPERIMENTAL

In this cohort of relatives, the investigators will evaluate the function of pancreatic α-islets and the counter-regulation mechanism. This evaluation will have two main objectives. The first objective will be to compare this counter-regulation mechanism between individuals without type 1 diabetes and patients with type 1 diabetes. The second objective is to determine whether the dysfunction of the counter-regulation mechanism in diabetic patients is solely due to type 1 diabetes or if there is a familial component to this dysfunction.

Diagnostic Test: Insulin-induced hypoglycemia test

Characterize the glycemic profile and α-cell function. (WP4)

EXPERIMENTAL

The aim is to assess residual function in patients with pancreatic disease, the phenomenon of counter-regulation and its impact on carbohydrate metabolism. To this end, IIH tests will be carried out in these patients, during which blood samples will be taken as in patients with type 1 diabetes (see above). This group of patients will also serve as a control group for the study of our diabetic patients. Patient with : exocrine dysfunction of the pancreas either as a consequence of cystic fibrosis or as a consequence of (sub)total pancreatectomy.

Diagnostic Test: Insulin-induced hypoglycemia test

Evaluate the phenomenon of counter-regulation in patients with proven growth hormone. (WP5)

ACTIVE COMPARATOR

These patients will serve as control groups for our GLUREDIA study to assess counter-regulation in our diabetic patients. Patient with : groth hormone or adrenal hormone deficiency and in healthy patients with no proven hormone deficiency.

Diagnostic Test: Insulin-induced hypoglycemia test

Study the link between the clinical characteristics of diabetic patients and their genome (WP6)

EXPERIMENTAL

For each participant, the investigators will study their clinical history and the evolution of their glycemic parameters from diagnosis to the date they agreed to take part in the study (retrospective analysis). Next, each patient's exome will be analyzed from a blood tube taken during a consultation following agreement to take part in the study. With these analyses, the investigators hope to gain a better understanding of the clinical course of our diabetic patients and their risk of severe hypoglycemia.

Other: Biological sample once

Evaluation of the circadian rhythm of glucagon (WP7)

EXPERIMENTAL

After recruitment, each participant will complete a questionnaire assessing their sensitivity to hypoglycemia. Based on their responses and phenotype, participants will be divided into two cohorts for analysis. Subsequently, a glucagon profile will be established for each participant through quarterly consultations involving blood samples taken by a pediatric nurse.

Diagnostic Test: Glucagon profile

Interventions

Insulin-induced hypoglycemia test DIAGNOSTIC_TEST

For these tests, multiple blood samples will be collected during insulin-induced hypoglycemia (stage 1 hypoglycemia is defined as a blood glucose level below 70 mg/dL, while stage 2 corresponds to values below 54 mg/dL). The tests will be conducted on patients who have fasted for at least 12 hours and will be supervised by a medical staff member trained to manage severe hypoglycemia.

Characterize the glycemic profile and α-cell function. (WP4); Evaluate the phenomenon of counter-regulation in patients with proven growth hormone. (WP5); Evaluate the α-cell function in first-degree relatives of patients with type 1 diabetes. (WP3); To investigate the evolution of pancreatic α-cell function. (WP1)

Glucagon profile DIAGNOSTIC_TEST

The subject must fast before the consultation and follow a specific diet the day before; after an initial blood draw (P1), the patient will have breakfast and take any required insulin, followed by two additional blood draws 1.5 hours after breakfast (P2) and 1.5 hours after P2 (P3)

Evaluation of the circadian rhythm of glucagon (WP7)

Biological sample once OTHER

The exome of each patient will then be analyzed from the blood sample taken beforehand.

Study the link between the clinical characteristics of diabetic patients and their genome (WP6)

Observation-questionnaire OTHER

only the answer to a questionnaire

Conduct an assessment of the management of severe hypoglycemia. (WP2)

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• De novo type 1 diabetic patient, as per ISPAD criteria;
• Symptoms of hyperglycemia: polyuria-polydipsia-amaigrin +/- Acido ketosis.
• Fasting blood glucose ≥126 mg/dL AND/OR blood glucose ≥200 mg/dL at 120 minutes of an OGTT AND/OR HbA1c ≥6.5% AND/OR a patient with symptoms of hyperglycemia/hyperglycemic crisis (see 8. a. 2.) with random blood glucose ≥200 mg/dL.
• Presence in serum of one or more anti-islet autoantibodies (anti-insulin, anti-IA2, anti-GAD65, anti-ZnT8)
• Patients aged between 2 and 30 years
• Minimum weight: 17 kg (for blood samples)
• Male - female patients
• Free, written and oral consent.

You may not qualify if:

• Child under 2 years of age.
• Taking treatments interfering with insulin secretion and sensitivity (e.g. sulfonylureas, diazoxide, somatostatin, methylxanthine derivatives, corticosteroids, biguanide, incretins).
• Obesity defined as a BMI with a z-score \>+3 SD.
• Hepatic, renal or adrenal insufficiency.
• History of bone marrow transplantation.
• History of diabetes after hemolytic-uremic syndrome.
• Epileptic patient
• Absence of anti-islet autoantibodies.
• Dysmorphia with suspicion of underlying genetic syndrome.
• Participation in another study in the previous 3 months, with administration of blood derivatives or potentially immunomodulating treatments.
• WP2 :
• De novo type 1 diabetic patient, as per ISPAD criteria;
• Symptoms of hyperglycemia: polyuria-polydipsia-amaigrin +/- Acido ketosis.
• Fasting blood glucose ≥126 mg/dL AND/OR blood glucose ≥200 mg/dL at 120 minutes of an OGTT AND/OR HbA1c ≥6.5% AND/OR a patient with symptoms of hyperglycemia/hyperglycemic crisis (see 8. a. 2.) with random blood glucose ≥200 mg/dL.
• Presence in serum of one or more anti-islet autoantibodies (anti-insulin, anti-IA2, anti-GAD65, anti-ZnT8)

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead
• The Leona M. and Harry B. Helmsley Charitable Trust: collaborator

Study Sites (1)

Clinique Universitaires Saint Luc

Brussels, Woluwe-saint-lambert, 1200, Belgium

RECRUITING

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Philippe Lysy, Pr

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philippe Lysy, Pr

CONTACT

027641370; antoine.harvengt@saintluc.uclouvain.be

Antoine Harvengt, Dr

CONTACT

027641370; antoine.harvengt@saintluc.uclouvain.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional study, parallel Assignment, the main objective is diagnostic, open-label, this study has 7 sub-sections.

Study Record Dates

• First Submitted: July 25, 2024
• First Posted: January 13, 2025
• Study Start: May 25, 2022
• Primary Completion: October 25, 2025
• Study Completion: October 25, 2025
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)