Severe Hypoglycemia, Type1diabetes
Conditions
Keywords
Pediatric, Hypoglycemia, Diabetes
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.
Interventions
DIAGNOSTIC_TESTInsulin-induced hypoglycemia 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.
DIAGNOSTIC_TESTGlucagon profile
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)
OTHERBiological sample once
The exome of each patient will then be analyzed from the blood sample taken beforehand.
OTHERObservation-questionnaire
only the answer to a questionnaire
Sponsors
The Leona M. and Harry B. Helmsley Charitable Trust
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Interventional study, parallel Assignment, the main objective is diagnostic, open-label, this study has 7 sub-sections.
Eligibility
Sex/Gender
ALL
Age
2 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
WP1 : * Inclusion criteria: * 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. *
Exclusion criteria
* Child under 2 years of age. * Taking treatments interfering with insulin secretion and sensitivity (e.g. sulfonylureas, diazoxide, somatostatin, methylxanthine derivatives, corticosteroids, biguanide, incretins). * Presence of newly diagnosed (within 1 month) celiac disease (diagnosed on pathological duodenal biopsy) at inclusion. * Autoimmune/autoinflammatory disease (other than type 1 diabetes) or active malignancy present at inclusion. * 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 : * Inclusion Criteria: * 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 years and 18 years (\<18 years). * Male - female patients * Free, written and oral consent. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the evolution of pancreatic α-cell function. (WP1) | 18 months per patient | Regular clinical and biological monitoring will be performed during this period as well as four insulin-induced hypoglycemia (IIH) tests. |
| To evaluate the presence of blood biomarkers that correlate with the evolution of α-cell function. (WP1) | 18 months per patient | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the glycemic profile and α-cell function. (WP4) | Baseline | IIH tests will be performed in these patients during which blood samples will be taken as in patients with type 1 diabetes. This group of patients will also be a control group for the study of our diabetic patients. (WP4) |
| Evaluate the phenomenon of counter-regulation in patients with proven growth hormone. (WP5) | Baseline | Patients suspected of adrenal or pituitary hormone deficiency, will perform as part of their diagnosis a hypoglycemic test. Here the difference is that the investigators will add two additional tubes to each sample, to those already collected as part of the hypoglycemic test. These tubes will be used, as in the other parts, to measure hormones and other blood parameters, as well as to perform an analysis of the genome, proteome and micro-RNAs (miRs). (WP5) |
| Conduct an assessment of the management of severe hypoglycemia. (WP2) | Baseline | Use of a questionnaire which is sent out once per patient during a routine consultation. The analysis does not take the form of a score, but is based on the analysis of the answers to the question according to the patient's profile. (WP2) |
| Evaluation of the circadian rhythm of glucagon (WP7) | Baseline | Each participant will complete a questionnaire assessing his or her susceptibility to hypoglycemia. A glucagonemic profile will then be established for each participant. This step, carried out during quarterly consultations, will involve blood sampling. (WP7) |
| Study the link between the clinical characteristics of diabetic patients and their genome (WP6) | Baseline | For each participant, the investigators will study their clinical history, the evolution of their glycemic parameters from diagnosis to the date they agree 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 inestigators hope to gain a better understanding of the clinical course of our diabetic patients and their risk of severe hypoglycemia. (WP6) |
| Evaluate the α-cell function in first-degree relatives of patients with type 1 diabetes. (WP3) | Baseline | In the remaining parents, those without biological signs of (pre-)diabetes, an IIH test will be performed during which blood samples identical to those performed in patients with type 1 diabetes will be taken. (WP3) |
Countries
Belgium
Contacts
Primary ContactPhilippe Lysy, Pr
Backup ContactAntoine Harvengt, Dr
Outcome results
None listed