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- Title
Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.
- Authors
Sheikh, Saba; Gudipaty, Lalitha; De Leon, Diva D.; Hadjiliadis, Denis; Kubrak, Christina; Rosenfeld, Nora K.; Nyirjesy, Sarah C.; Peleckis, Amy J.; Malik, Saloni; Stefanovski, Darko; Cuchel, Marina; Rubenstein, Ronald C.; Kelly, Andrea; Rickels, Michael R.
- 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 pancreatic-sufficient 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 α-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.
- Subjects
HYPERGLYCEMIA; CYSTIC fibrosis; EXOCRINE pancreatic insufficiency; GLUCOSE tolerance tests; PANCREATIC beta cells; INSULIN regulation; GLUCAGON-like peptide 1; PATIENTS; PHYSIOLOGY; DISEASE risk factors
- Publication
Diabetes, 2017, Vol 66, Issue 1, p134
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0394