Hypoglycemia and Glucagon Response in CF

Completed

• Conditions: Hypoglycemia; Cystic Fibrosis; Glucagon Deficiency; Pancreatic Insufficiency

• Registration Number: NCT05700604
• Lead Sponsor: Marmara University

Brief Summary

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:

1. Do isolated hypoglycemia and hypoglycemia with abnormal glucose tolerance have different etiopathogenesis?

2. 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

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.

Study Timeline

• Study Start: 2020-01-01
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2023-01
• Study First Submitted: 2023-01-02
• Study First Submitted QC: 2023-01-25
• Last Update Submitted: 2023-01-25
• Study First Posted: 2023-01-26
• Last Update Posted: 2023-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change of glucose level	0-30-60-90-120-150-180.minutes of oral glucose loading	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.
Change of insulin level	0-30-60-90-120-150-180.minutes of oral glucose loading	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.
Change of glucagon level	0-60-120-150-180.minutes of oral glucose loading	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Marmara University, School of Medicine; 🇹🇷 Istanbul, Turkey