title: Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.
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.
authors: Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
authors: Saba
authors: S
authors: Sheikh
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Lalitha
authors: L
authors: Gudipaty
authors: Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
authors: Diva D
authors: DD
authors: De Leon
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Denis
authors: D
authors: Hadjiliadis
authors: Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
authors: Christina
authors: C
authors: Kubrak
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Nora K
authors: NK
authors: Rosenfeld
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Sarah C
authors: SC
authors: Nyirjesy
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Amy J
authors: AJ
authors: Peleckis
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Saloni
authors: S
authors: Malik
authors: Department of Biostatistics, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA.
authors: Darko
authors: D
authors: Stefanovski
authors: Division of Translational Medicine and Human Genetics, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors: Marina
authors: M
authors: Cuchel
authors: Division of Pulmonary Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
authors: Ronald C
authors: RC
authors: Rubenstein
authors: Division of Endocrinology and Diabetes, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
authors: Andrea
authors: A
authors: Kelly
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA rickels@mail.med.upenn.edu.
authors: Michael R
authors: MR
authors: Rickels
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology*; D010188:Exocrine Pancreatic Insufficiency / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D011384:Proinsulin / Q000378:metabolism; D055815:Young Adult
chemical_list: D002096:C-Peptide; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D011384:Proinsulin; D005947:Glucose