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.
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.
Patients aged between 2 and 30 years
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.
Parallel
Insulin-induced hypoglycemia test
Diagnostic testFor 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.
Glucagon profile
Diagnostic testThe 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)
Biological sample once
Other interventionThe exome of each patient will then be analyzed from the blood sample taken beforehand.
Observation-questionnaire
Other interventiononly the answer to a questionnaire
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Treatment groupsSee each treatment group below.
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.
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.
Conduct an assessment of the management of severe hypoglycemia. (WP2)
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)
Evaluate the α-cell function in first-degree relatives of patients with type 1 diabetes. (WP3)
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)
Characterize the glycemic profile and α-cell function. (WP4)
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)
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)
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Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Lead sponsor
The Leona M. and Harry B. Helmsley Charitable Trust
Collaborator
