title: Insulin resistance with altered secretory kinetics and reduced proinsulin in cystic fibrosis patients.
abstract: BACKGROUND
  Impaired glucose tolerance and secondary diabetes are frequent in older patients with cystic fibrosis (CF), associated with increased frequency of infections and reduced life expectancy. Studies on the pathophysiology of islet cell secretion in CF are a prerequisite for a scientifically based therapeutic approach.
  
  
  METHODS
  Oral glucose tolerance tests were performed in 71 patients (14.2 +/- 0.5 years; mean +/- SE) and 56 control subjects (16.5 +/- 0.9 years). Glucose, insulin, C-peptide, and proinsulin were measured every 30 min.
  
  
  RESULTS
  Glucose tolerance in CF patients was classified as normal (NGT, n = 48), impaired (IGT, n = 14), or diabetic (DM, n = 9). Even in CF patients with NGT, blood glucose was significantly elevated at 30, 60, and 90 min of the test. Surprisingly, the secretory responses of insulin and C-peptide were not reduced in CF patients with IGT or DM compared with both healthy controls or CF patients with normal glucose tolerance. However, peak insulin concentration was reached at 90 min in CF-IGT or CF-DM patients compared with 30 min in controls. The ratio of glucose to insulin, an indicator of insulin resistance, increased in CF patients with progression of carbohydrate intolerance. Proinsulin was significantly reduced in all CF patients compared with controls (p < 0.001; Wilcoxon's rank sum test).
  
  
  CONCLUSIONS
  In CF patients with impaired glucose tolerance or diabetes, integrated insulin release is not diminished, indicating that insulin resistance is likely to contribute to hyperglycemia in CF patients with IGT or DM. Reduced proinsulin levels in CF patients are compatible either with enhanced conversion of proinsulin to insulin in compensation for reduced beta-cell mass, or enhanced clearance of proinsulin.
authors.affiliation: Department of Pediatrics I, University of Ulm, Germany.
authors.forename: R W
authors.initials: RW
authors.lastname: Holl
authors.forename: A
authors.initials: A
authors.lastname: Wolf
authors.forename: A
authors.initials: A
authors.lastname: Thon
authors.forename: M
authors.initials: M
authors.lastname: Bernhard
authors.forename: C
authors.initials: C
authors.lastname: Buck
authors.forename: M
authors.initials: M
authors.lastname: Missel
authors.forename: E
authors.initials: E
authors.lastname: Heinze
authors.forename: H
authors.initials: H
authors.lastname: von der Hardt
authors.forename: W M
authors.initials: WM
authors.lastname: Teller
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis* / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D011384:Proinsulin / Q000097:blood*; D012016:Reference Values; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin