title: Mechanisms of glucose intolerance in cystic fibrosis.
abstract: OBJECTIVE
  Although cystic fibrosis-related diabetes (CFRD), a poor prognostic factor in cystic fibrosis (CF), is characterized by insulinopenia, the role of insulin resistance is unclear. Using a prospective study design, we measured insulin resistance, pancreatic beta-cell function and correlated glycaemic status with clinical parameters.
  
  
  METHODS
  Oral glucose tolerance test was performed in 60 stable adult CF patients. Insulin sensitivity and beta-cell function were measured using the homeostatic model assessment (HOMA2), Stumvoll and oral glucose insulin sensitivity (OGIS) indices.
  
  
  RESULTS
  Forty-two (70%) had normal glucose tolerance (NGT), 10 (17%) impaired glucose tolerance (IGT) and eight (13%) CFRD. There was no difference in insulin sensitivity among the three groups (HOMA2: NGT 280, IGT 250, CFRD 339, P = 0.42; Stumvoll: NGT 0.128, IGT 0.126, CFRD 0.129, P = 0.76; and OGIS: NGT 515, IGT 472, CFRD 472, P = 0.12). Pancreatic beta-cell function (CFRD 50% vs. NGT 67%; P < 0.05) and first-phase insulin secretion were reduced in CFRD (250 vs. NGT 509; P = 0.004). First-phase insulin secretion was inversely correlated with 1-h (r = -0.74; P < 0.0001) and 2-h glucose levels (r = -0.34; P < 0.05). There was no difference in body mass index or poor lung function (forced expiratory volume in 1 s: CFRD 54% vs. NGT 65%; P = 0.43). However, there were more hospital admissions in the CFRD group (three vs. NGT one per patient per year; P < 0.05).
  
  
  CONCLUSIONS
  CFRD is characterized by qualitative and quantitative defects in insulin secretion, but not insulin resistance, and is associated with increased hospital admissions for pulmonary exacerbations.
authors.affiliation: The Adult Cystic Fibrosis Unit, The Cardiothoracic Centre NHS Trust, Liverpool L143PE, UK.
authors.forename: K
authors.initials: K
authors.lastname: Mohan
authors.forename: H
authors.initials: H
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Dyce
authors.forename: R
authors.initials: R
authors.lastname: Grainger
authors.forename: R
authors.initials: R
authors.lastname: Hughes
authors.forename: J
authors.initials: J
authors.lastname: Vora
authors.forename: M
authors.initials: M
authors.lastname: Ledson
authors.forename: M
authors.initials: M
authors.lastname: Walshaw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications*; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology*; D004812:Epidemiologic Methods; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology*; D005951:Glucose Tolerance Test; D038321:Glycemic Index; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin