title: Insulin sensitivity and insulin clearance in cystic fibrosis patients with normal and diabetic glucose tolerance.
abstract: OBJECTIVE
  We studied glucose metabolism and insulin kinetics in cystic fibrosis patients with diabetic and normal glucose tolerance.
  
  
  METHODS
  Measurements of blood glucose and serum free insulin concentrations during hyperinsulinaemic normoglycaemic clamp and post-clamp insulin decay, followed by the calculation of insulin sensitivity (M-value and M/I ratio), insulin clearance rate, serum half-life and apparent distribution space for insulin.
  
  
  METHODS
  Cystic fibrosis patients, age range 20-29 years, with diabetes mellitus (n = 10) and normal glucose tolerance (n = 10), and 10 age-matched control subjects.
  
  
  RESULTS
  During the glucose clamp, diabetic cystic fibrosis patients needed less glucose than cystic fibrosis patients with normal glucose tolerance and control subjects (M-value), and steady-state serum insulin concentrations were lower in cystic fibrosis patients with diabetic and normal glucose tolerance than in control subjects. The quantity of glucose metabolized per unit of serum insulin concentration (M/I ratio) was similar in the three study groups (median approximately 145 (mumol/kg/min)/(nmol/l); range 70-252). Insulin clearance rates were higher in cystic fibrosis patients with diabetic (24.4 (19.3-29.9) ml/kg/min) and normal (22.6 (14.9-28.4) ml/kg/min) glucose tolerance than in control subjects (17.5 (15.9-24.2) ml/kg/min). Although insulin clearance rates were inversely related to body mass index (R(S) = -0.59, P < 0.001), the higher insulin clearance rates in CF patients cannot be accounted for solely by differences in body mass index since the insulin clearance rates were similarly increased in patients with body mass index above and below 20 kg/m2 (22.7 (14.9-28.4) and 24.4 (19.3-29.9) ml/kg/min, respectively). Serum half-lives for insulin were shorter in cystic fibrosis patients (approximately 4.3 (3.2-7.2) min) than in control subjects (5.9 (3.8-12.5) min), whereas the apparent distribution spaces for insulin were similar in the three study groups (approximately 150 (88-391) ml/kg).
  
  
  CONCLUSIONS
  Insulin sensitivity, calculated as the quantity of glucose metabolized per kg body weight per unit of serum insulin concentration, is normal in cystic fibrosis patients with normal glucose tolerance and with well controlled diabetes mellitus. The insulin clearance rate is increased in cystic fibrosis patients with diabetic and normal glucose tolerance, owing to a shorter serum half-life of insulin, whereas the apparent distribution space for insulin is normal.
authors.affiliation: CF Center Copenhagen, Department of Pediatrics, Rigshospitalet, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Lanng
authors.forename: B
authors.initials: B
authors.lastname: Thorsteinsson
authors.forename: M E
authors.initials: ME
authors.lastname: Røder
authors.forename: J
authors.initials: J
authors.lastname: Nerup
authors.forename: C
authors.initials: C
authors.lastname: Koch
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003550:Cystic Fibrosis / Q000150:complications / Q000378:metabolism*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D001786:Blood Glucose; D007328:Insulin