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

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 minutesof an OGTT AND/OR HbA1c ≥6.5% AND/OR a patient with symptoms ofhyperglycemia/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 onpathological duodenal biopsy) at inclusion.

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy 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 ofblood 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 minutesof an OGTT AND/OR HbA1c ≥6.5% AND/OR a patient with symptoms ofhyperglycemia/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.

• Exclusion criteria:

• Child under 2 years of age.

• Taking treatments that interfere 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 onpathological duodenal biopsy) at inclusion.

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy 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.

• Absence of anti-islet autoantibodies.

• Dysmorphia with suspected underlying genetic syndrome.

• Participation in another study within the previous 3 months with administrationof blood derivatives or potentially immunomodulatory treatments.

WP3 :

• Inclusion Criteria:

• Adult older than 18 years.

• Absence of blood marker of diabetes (Absence of antibodies, HbA1C <6.5%,C-peptide > 0.18 nmol/L, Fasting blood glucose < 100 mg/dL, blood glucose atany time < 200 mg/dL).

• Be a first-degree relative with a patient being followed for diabetes (meetingISPAD criteria).

• Male - Female

• Free written and oral consent

• Exclusion criteria:

• Taking treatments that interfere 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 onpathological duodenal biopsy) at inclusion.

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy 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.

• Ischemic cardiomyopathy

• Pregnant participant

• Epileptic patient

WP4 :

• Inclusion Criteria:

Cohort of patients followed for cystic fibrosis:

• Pediatric patient between 2 and 18 years of age.

• Diagnosed with cystic fibrosis with impaired pancreatic endocrine function.

• Presents glucose homeostasis disorders (regular hypo/hyper-glycemia).

• Male - female patient

• Free, written and oral consent

Cohort of patients with (sub)total pancreatectomy:

• Pediatric patients between 2 and 18 years of age.

• Follow-up for total pancreatectomy or caudal pancreatectomy

• Presents disorders of carbohydrate homeostasis (regular hypo-/hyper-glycemia)

• Male - female patient

• Free, written and oral consent

• Exclusion criteria:

• Child under 2 years of age.

• Body weight less than 17 kg.

• Taking treatments that interfere 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 onpathological duodenal biopsy) at inclusion.

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy 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.

• Dysmorphia with suspected underlying genetic syndrome.

• Participation in another study within the last 3 months, with administration ofblood derivatives or potentially immunomodulatory treatments.

WP5 :

• Inclusion Criteria:

• Patient who has undergone insulin testing due to suspected growth hormonedeficiency or adrenal insufficiency or hypopituitarism.

• Patients between the ages of 2 years and 18 years (<18 years).

• Male - female patient.

• Free written and oral consent.

• Exclusion criteria:

• Child under 2 years of age.

• Body weight less than 17 kg.

• Taking treatments that interfere 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 onpathological duodenal biopsy) at inclusion.

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy present at inclusion.

• Obesity defined as a BMI with a z-score >+3 SD..

• History of bone marrow transplantation.

• History of diabetes after hemolytic-uremic syndrome.

• Participation in another study within the last 3 months, with administration ofblood derivatives or potentially immunomodulatory treatments.

WP6 :

• Inclusion Criteria:

• 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 minutesof an OGTT AND/OR HbA1c ≥6.5% AND/OR a patient with symptoms ofhyperglycemia/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 18 years (<18 years).

• 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).

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy 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

• Dysmorphia with suspicion of underlying genetic syndrome.

• Participation in another study in the previous 3 months, with administration ofblood derivatives or potentially immunomodulating treatments.

WP7 :

• 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 minutesof an OGTT AND/OR HbA1c ≥6.5% AND/OR a patient with symptoms ofhyperglycemia/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 18 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 onpathological duodenal biopsy) at inclusion.

• Autoimmune/autoinflammatory disease (other than type 1 diabetes) or activemalignancy 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 ofblood derivatives or potentially immunomodulating treatments.