title: Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients.
abstract: BACKGROUND
  Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.
  
  
  OBJECTIVE
  To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.
  
  
  METHODS
  A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.
  
  
  RESULTS
  Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6  pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7  pmol/min per m(2) per mM per year (confidence interval (CI) -4.5 to -0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.
  
  
  CONCLUSIONS
  The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.
authors.affiliation: International Center for the Assessment of Nutritional Status - DiSTAM, Università degli Studi di Milano, Via Botticelli, 21, 20133 Milan, Italy. alberto.battezzati@unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Battezzati
authors.forename: A
authors.initials: A
authors.lastname: Mari
authors.forename: L
authors.initials: L
authors.lastname: Zazzeron
authors.forename: G
authors.initials: G
authors.lastname: Alicandro
authors.forename: L
authors.initials: L
authors.lastname: Claut
authors.forename: P M
authors.initials: PM
authors.lastname: Battezzati
authors.forename: C
authors.initials: C
authors.lastname: Colombo
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000209:etiology*; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male
chemical_list: D002096:C-Peptide; D007328:Insulin