Hypoglycemia and Glucagon Response in CF

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate the etiopathogenesis of isolated hypoglycemia and hypoglycemia with abnormal glucose tolerance in children with Cystic Fibrosis (CF) and to evaluate the role of glucagon and pancreatic insufficiency on hypoglycemia in CF. The main questions it aims to answer are: Do isolated hypoglycemia and hypoglycemia with abnormal glucose tolerance have different etiopathogenesis? What is the role of pancreatic insufficiency in these two conditions? Participants were asked to perform 3-h OGTT and to take blood samples. Researchers compared with healthy peers to see if there is isolated hypoglycemia in OGTT and how is the glucagon response to OGTT in healthy peers.

Detailed Description
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The exact underlying mechanism of hypoglycemia in CF is still unknown. Some recent studies support the delayed and prolonged insulin secretion and impaired counterregulatory hormone response as the reason of reactive hypoglycemia, whereas the others argued an additive effect of an intrinsic factor. However, the weakness of these limited studies is that nearly all of them included CF patients who had pancreatic insufficiency (PI) and could not reveal the mechanism of hypoglycemia seen in those without PI. In addition, there were no healthy controls for comparison of glucagon secretion in CF patients with hypoglycemia. Moreover, the studies that evaluate the role of glucagon in hypoglycemic CF patients were performed in hypoglycemic adult patients with abnormal glucose tolerance (AGT) and the delayed and prolonged insulin release is expected to be more likely as the reason of hypoglycemia in this setting. Previously, the investigators had demonstrated isolated hypoglycemia in some of the pediatric CF patients during OGTT. In this study, the investigators aimed to further investigate possible mechanisms of hypoglycemia. The investigators hypothesized that the mechanism of isolated hypoglycemia might be different from hypoglycemia seen in patients with AGT. Furthermore, the investigators evaluated the role of pancreatic insufficiency in hypoglycemia of CF patients by analyzing glucose, insulin and glucagon response to a glucose load in CF patients with and without PI.

Official Title
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The Effect of Pancreatic Insufficiency on Hypoglycemia and Glucagon Response in Children With Cystic Fibrosis

Conditions
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Cystic Fibrosis, Hypoglycemia, Glucagon Deficiency, Pancreatic Insufficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 10-18 year-old children genetically diagnosed with Cystic Fibrosis Regularly followed by the department of pediatric endocrinology Exclusion Criteria: Using corticosteroid therapy in the last 3 months Those who had acute exacerbation in the last 3 months Previously diagnosed with diabetes

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cystic Fibrosis<br>10-18 year-old children with Cystic Fibrosis | |
| Healthy Controls<br>age and sex matched healthy controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of glucose level | A 3 hour Oral Glucose Tolerance Test (OGTT) was used to evaluate changing and it was performed in the morning following overnight fasting of ≥8 hours. All participants (CF patients and controls) received oral glucose solution (1.75 g/kg; max: 75 g) in 10 minutes. | 0-30-60-90-120-150-180.minutes of oral glucose loading | 
| Change of insulin level | A 3 hour Oral Glucose Tolerance Test (OGTT) was used to evaluate changing and it was performed in the morning following overnight fasting of ≥8 hours. All participants (CF patients and controls) received oral glucose solution (1.75 g/kg; max: 75 g) in 10 minutes. | 0-30-60-90-120-150-180.minutes of oral glucose loading | 
| Change of glucagon level | A 3 hour Oral Glucose Tolerance Test (OGTT) was used to evaluate changing and it was performed in the morning following overnight fasting of ≥8 hours. All participants (CF patients and controls) received oral glucose solution (1.75 g/kg; max: 75 g) in 10 minutes. | 0-60-120-150-180.minutes of oral glucose loading | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | It was measured by high-performance liquid chromatographic (HPLC) method from venous blood sample | 0.minute of oral glucose loading | 
| C-reactive protein (CRP) | It was measured by ELISA from venous blood sample | 0.minute of oral glucose loading | 
| Cortisol | The response to hypoglycemia was evaluated during 3 hour Oral Glucose Tolerance Test (OGTT) | 0-180.minutes of oral glucose loading | 
| Forced expiratory volume in 1 second (FEV1) | It was measured by spirometry | Within 2 weeks before OGTT | 
| Body Mass Index (BMI) | It was calculated as weight (kg)/height (m)2 | Within 24 hours of OGTT |