Hypoglycemia and Glucagon Response in CF

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05700604
• Other study ID #: 09.2019.933
• Status: Completed
• Start date: January 1, 2020
• Est. completion date: December 31, 2020

Study information

• Verified date: January 2023
• Source: Marmara University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Exocrine Pancreatic Insufficiency
• Fibrosis
• Glucagon Deficiency
• Hypoglycemia
• Pancreatic Insufficiency

Locations

Country	Name	City	State
Turkey	Marmara University, School of Medicine	Istanbul

Sponsors (2)

Lead Sponsor	Collaborator
Marmara University	Yeditepe University

Country where clinical trial is conducted

Turkey, 

References & Publications (4)

Aitken ML, Szkudlinska MA, Boyko EJ, Ng D, Utzschneider KM, Kahn SE. Impaired counterregulatory responses to hypoglycaemia following oral glucose in adults with cystic fibrosis. Diabetologia. 2020 May;63(5):1055-1065. doi: 10.1007/s00125-020-05096-6. Epub — View Citation

Armaghanian N, Hetherington J, Parameswaran V, Chua EL, Markovic TP, Brand-Miller J, Steinbeck K. Hypoglycemia in cystic fibrosis during an extended oral glucose tolerance test. Pediatr Pulmonol. 2020 Dec;55(12):3391-3399. doi: 10.1002/ppul.25081. Epub 20 — View Citation

Kilberg MJ, Harris C, Sheikh S, Stefanovski D, Cuchel M, Kubrak C, Hadjiliadis D, Rubenstein RC, Rickels MR, Kelly A. Hypoglycemia and Islet Dysfunction Following Oral Glucose Tolerance Testing in Pancreatic-Insufficient Cystic Fibrosis. J Clin Endocrinol — View Citation

Kilberg MJ, Sheikh S, Stefanovski D, Kubrak C, De Leon DD, Hadjiliadis D, Rubenstein RC, Rickels MR, Kelly A. Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia. J Cyst Fibros. 2020 Mar;19(2):310-315. doi: 10.1 — View Citation

Outcome

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