Reduced β-cell secretory capacity in pancreatic-insufficient, but not pancreatic-sufficient, cystic fibrosis despite normal glucose tolerance

Saba Sheikh, Lalitha Gudipaty, Diva D. De Leon, Denis Hadjiliadis, Christina Kubrak, Nora K. Rosenfeld, Sarah C. Nyirjesy, Amy J. Peleckis, Saloni Malik, Darko Stefanovski, Marina Cuchel, Ronald C. Rubenstein, Andrea Kelly, Michael R. Rickels

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreaticsufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and a-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.

Original languageEnglish
Pages (from-to)134-144
Number of pages11
JournalDiabetes
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2017

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