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J Cyst Fibros. 2019 Aug 8. pii: S1569-1993(19)30827-6. doi: 10.1016/j.jcf.2019.07.006. [Epub ahead of print]

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

Author information

1
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: kilbergm@email.chop.edu.
2
Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
3
Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
4
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
5
Division of Pulmonary and Critical Care Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
6
Division of Endocrinology, Diabetes & Metabolism, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

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.

KEYWORDS:

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

PMID:
31402215
DOI:
10.1016/j.jcf.2019.07.006

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