Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance
| Autor: | Darko Stefanovski, Michael R. Rickels, Diva D. De León, Ronald C. Rubenstein, Andrea Kelly, Saloni Malik, Nora K Rosenfeld, Saba Sheikh, Sarah Nyirjesy, Amy J. Peleckis, Christina Kubrak, Denis Hadjiliadis, Marina Cuchel, Lalitha Gudipaty |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Glucose tolerance test medicine.diagnostic_test Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Secretory Rate Incretin 030209 endocrinology & metabolism Biology medicine.disease Glucagon 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Gastric inhibitory polypeptide Diabetes mellitus Internal medicine Internal Medicine medicine Proinsulin |
| Zdroj: | Diabetes. 66:134-144 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db16-0394 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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