Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia

Marissa J. Kilberg, Saba Sheikh, Darko Stefanovski, Christina Kubrak, Diva D. De Leon, Denis Hadjiliadis, Ronald C. Rubenstein, Michael R. Rickels, Andrea Kelly

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear. Methods: To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF). Results: Hypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120–210) minutes following initial meal ingestion. Hypoglycemia[+] and hypoglycemia[−] groups did not differ in gender, age, lung function, HbA1c, or BMI. While 11/14 hypoglycemia[−] individuals displayed normal glucose tolerance (NGT), only 2/9 hypoglycemia[+] had NGT. Peak glucose was higher in hypoglycemia[+] vs hypoglycemia[−]. Compared to hypoglycemia[−] NGT, hypoglycemia[+] exhibited lower early-phase insulin secretion (ISR-AUC0-30min). ISR-AUC120–180min was not different in hypoglycemia[+] vs hypoglycemia[−] with abnormal glucose tolerance (AGT); however, glucose-AUC120–180min was lower in hypoglycemia[+] vs hypoglycemia[−] AGT. After adjusting for glucose-AUC, hypoglycemia[+] subjects tended to have higher ISR-AUC120–180min than hypoglycemia[−] AGT. Glucagon concentration did not differ between groups. Lower GLP-1-AUC30min and AUC180min and higher GIP-AUC30min were present in hypoglycemia[+] individuals. Conclusion: Hypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC30min), and possibly late compensatory hyperinsulinemia. Further study is required to understand whether absence of glucagon difference in the hypoglycemia[+] individuals signals counterregulatory impairment, to delineate the role of incretins in hypoglycemia, and to determine the relationship of hypoglycemia to emergence of CFRD.

Original languageEnglish
Pages (from-to)310-315
Number of pages6
JournalJournal of Cystic Fibrosis
Volume19
Issue number2
DOIs
StatePublished - Mar 2020

Keywords

  • Cystic fibrosis
  • Glucose tolerance
  • Hypoglycemia
  • Insulin secretion
  • Pancreatic insufficiency

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