title: Insulin production and resistance in cystic fibrosis: effect of age, disease activity, and genotype.
abstract: OBJECTIVE
  To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD).
  
  
  METHODS
  One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic β-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR).
  
  
  RESULTS
  The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes.
  
  
  CONCLUSIONS
  IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, β-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.
authors.affiliation: Department of Paediatrics, University Hospital of Parma, Parma, Italy. mariaelisabeth.street@unipr.it
authors.forename: M E
authors.initials: ME
authors.lastname: Street
authors.forename: C
authors.initials: C
authors.lastname: Spaggiari
authors.forename: M A
authors.initials: MA
authors.lastname: Ziveri
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Volta
authors.forename: I
authors.initials: I
authors.lastname: Viani
authors.forename: G L
authors.initials: GL
authors.lastname: Grzincich
authors.forename: C
authors.initials: C
authors.lastname: Sartori
authors.forename: M
authors.initials: M
authors.lastname: Zanzucchi
authors.forename: V
authors.initials: V
authors.lastname: Raia
authors.forename: C
authors.initials: C
authors.lastname: Terzi
authors.forename: G
authors.initials: G
authors.lastname: Pisi
authors.forename: E
authors.initials: E
authors.lastname: Zanetti
authors.forename: M C S
authors.initials: MC
authors.lastname: Boguszewski
authors.forename: T O
authors.initials: TO
authors.lastname: Kamoi
authors.forename: S
authors.initials: S
authors.lastname: Bernasconi
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000096:biosynthesis* / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology; D008168:Lung / Q000502:physiology; D008297:Male; D055815:Young Adult
chemical_list: D002096:C-Peptide; D007328:Insulin