title: Age- and Sex-Dependent Distribution of OGTT-Related Variables in a Population of Cystic Fibrosis Patients.
abstract: BACKGROUND
  Cystic fibrosis (CF) causes an exceptionally high prevalence of diabetes that increases with age, especially in females. The glucose tolerance defect is progressive, but a cystic fibrosis transmembrane conductance regulator-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear.
  
  
  OBJECTIVE
  The objective of the study was to analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF.
  
  
  METHODS
  This was a cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5 y).
  
  
  METHODS
  The study was conducted at the CF Center of Milan.
  
  
  METHODS
  The study included 187 patients aged 8-30 years.
  
  
  METHODS
  Interventions included 3-hour oral glucose tolerance tests (n = 478) with 30-minute insulin and c-peptide sampling.
  
  
  METHODS
  Model-derived insulin secretory and sensitivity parameters were measured.
  
  
  RESULTS
  Age was associated with a progressive decrement in insulinemia (at 30 min) and a subsequent increment in glycemia (at 60-90 min), returning at or below baseline (at 180 min). These changes are explained by a progressive reduction in β-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared with males, females display higher glucose, insulin, and c-peptide responses with greater insulin secretion, β-cell sensitivity to glucose, insulin clearance, and equal insulin sensitivity.
  
  
  CONCLUSIONS
  A defect in β-cell sensitivity to glucose progressively develops with age, but it is not sex specific and does not explain the worse glucose tolerance reported in females. In contrast, insulin clearance increases with age, especially in females, contributing to the deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating oral glucose tolerance test results in CF patients.
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Battezzati
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bedogni
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zazzeron
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Pier Maria
authors.initials: PM
authors.lastname: Battezzati
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Alicandro
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bertoli
authors.affiliation: International Center for the Assessment of Nutritional Status (A.B., G.B., S.B.), DeFENS, and Department of Health Sciences (P.M.B.), School of Medicine Ospedale San Paolo, Università degli Studi di Milano, 20122 Milano, Italy; Cystic Fibrosis Center (L.Z., G.A., C.C.), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy; and Institute of Neuroscience (A.M.), National Research Council, 27100 Padova, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D012737:Sex Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose