Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

Autor:	Sheikh S; Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA., Gudipaty L; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., De Leon DD; Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA., Hadjiliadis D; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., Kubrak C; Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA., Rosenfeld NK; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., Nyirjesy SC; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., Peleckis AJ; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., Malik S; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., Stefanovski D; Department of Biostatistics, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA., Cuchel M; Division of Translational Medicine and Human Genetics, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA., Rubenstein RC; Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA., Kelly A; Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA., Rickels MR; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA rickels@mail.med.upenn.edu.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2017 Jan; Vol. 66 (1), pp. 134-144. Date of Electronic Publication: 2016 Aug 05.
DOI:	10.2337/db16-0394
Abstrakt:	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. (© 2017 by the American Diabetes Association.)
Databáze:	MEDLINE
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