TY - JOUR
T1 - Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia
AU - Kilberg, Marissa J.
AU - Sheikh, Saba
AU - Stefanovski, Darko
AU - Kubrak, Christina
AU - De Leon, Diva D.
AU - Hadjiliadis, Denis
AU - Rubenstein, Ronald C.
AU - Rickels, Michael R.
AU - Kelly, Andrea
N1 - Publisher Copyright:
© 2019 European Cystic Fibrosis Society.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Cystic fibrosis
KW - Glucose tolerance
KW - Hypoglycemia
KW - Insulin secretion
KW - Pancreatic insufficiency
UR - http://www.scopus.com/inward/record.url?scp=85070195694&partnerID=8YFLogxK
U2 - 10.1016/j.jcf.2019.07.006
DO - 10.1016/j.jcf.2019.07.006
M3 - Article
C2 - 31402215
AN - SCOPUS:85070195694
SN - 1569-1993
VL - 19
SP - 310
EP - 315
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
IS - 2
ER -