title: Insulin resistance, β-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.
abstract: BACKGROUND
  diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis.
  
  
  OBJECTIVE
  To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes.
  
  
  METHODS
  It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured.
  
  
  RESULTS
  Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT.
  
  
  CONCLUSIONS
  In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic mechanism.
authors.affiliation: Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, España. Electronic address: mcanomegias@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Cano Megías
authors.affiliation: Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, España.
authors.forename: Olga
authors.initials: O
authors.lastname: González Albarrán
authors.affiliation: Servicio de Medicina Interna, Hospital Quirón San Camilo, Madrid, España.
authors.forename: Pablo
authors.initials: P
authors.lastname: Guisado Vasco
authors.affiliation: Servicio de Pediatría, Unidad de fibrosis quística, Hospital Universitario Ramón y Cajal, Madrid, España.
authors.forename: Adelaida
authors.initials: A
authors.lastname: Lamas Ferreiro
authors.affiliation: Servicio de Neumología, Hospital Universitario Ramón y Cajal, Madrid, España.
authors.forename: Luis
authors.initials: L
authors.lastname: Máiz Carro
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D010188:Exocrine Pancreatic Insufficiency / Q000209:etiology; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000032:analysis* / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008168:Lung / Q000503:physiopathology; D008297:Male; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: 2-hour oral glucose tolerance test; Cystic fibrosis; Diabetes; Fibrosis quística; Función de célula β; Insulin resistance; Resistencia a la insulina; Test de tolerancia oral a la glucosa a las 2 horas; β-cell function