Clinical trial NCT05700604: Hypoglycemia and Glucagon Response in CF
Official title: The Effect of Pancreatic Insufficiency on Hypoglycemia and Glucagon Response in Children With Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Hypoglycemia
Glucagon Deficiency
Pancreatic Insufficiency
Lead sponsor: Marmara University
Sponsor class: OTHER
Collaborators: name: Yeditepe University
First posted: 2023-01-26
Enrollment: 53
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population is the children and adolescents aged 10-18 years with CF who were regularly followed-up at the Pediatric Endocrinology and Diabetes Units.

The control group was age-matched healthy, diabetes non-diabetic siblings of patients with type 1 diabetes. All the controls were negative for β-cell autoantibodies (anti-glutamic acid decarboxylase, islet cell antibody, and insulin antibody).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of glucose level
timeFrame: 0-30-60-90-120-150-180.minutes of oral glucose loading
measure: Change of insulin level
timeFrame: 0-30-60-90-120-150-180.minutes of oral glucose loading
measure: Change of glucagon level
timeFrame: 0-60-120-150-180.minutes of oral glucose loading
Secondary outcomes:
measure: HbA1c
timeFrame: 0.minute of oral glucose loading
measure: C-reactive protein (CRP)
timeFrame: 0.minute of oral glucose loading
measure: Cortisol
timeFrame: 0-180.minutes of oral glucose loading
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: Within 2 weeks before OGTT
measure: Body Mass Index (BMI)
timeFrame: Within 24 hours of OGTT
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Marmara University, School of Medicine
Study officials:
affiliation: Marmara University, School of Medicine, Department of Pediatric Endocrinology
name: Belma Haliloglu, MD,PhD
role: STUDY_DIRECTOR
References:
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: 10.1016/j.jcf.2019.07.006. Epub 2019 Aug 8.
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 Metab. 2020 Oct 1;105(10):3179-89. doi: 10.1210/clinem/dgaa448.
citation: 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 2020 Jan 29.
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 2020 Oct 16.