Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia.
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.
['Kilberg|Marissa J|MJ|', 'Sheikh|Saba|S|', 'Stefanovski|Darko|D|', 'Kubrak|Christina|C|', 'De Leon|Diva D|DD|', 'Hadjiliadis|Denis|D|', 'Rubenstein|Ronald C|RC|', 'Rickels|Michael R|MR|', 'Kelly|Andrea|A|']
D000293:Adolescent D019540:Area Under Curve D001786:Blood Glucose D002096:C-Peptide D003550:Cystic Fibrosis D010188:Exocrine Pancreatic Insufficiency D005260:Female D005934:Glucagon D018149:Glucose Intolerance D005951:Glucose Tolerance Test D006801:Humans D007003:Hypoglycemia D054795:Incretins D007328:Insulin D000078790:Insulin Secretion D008297:Male D055815:Young Adult
Pancreatic insufficiency Cystic fibrosis Hypoglycemia Glucose tolerance Insulin secretion