Mechanisms of glucose intolerance in cystic fibrosis

Diabet Med. 2009 Jun;26(6):582-8. doi: 10.1111/j.1464-5491.2009.02738.x.

Abstract

Aims: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / metabolism*
  • Cystic Fibrosis / blood
  • Cystic Fibrosis / complications*
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / etiology*
  • Epidemiologic Methods
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / etiology*
  • Glucose Tolerance Test
  • Glycemic Index
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Blood Glucose
  • Insulin