title: Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study.
abstract: BACKGROUND
  A marked reduction in serum levels of bioactive insulin-like growth factor-I (IGF-I) has been observed in fasting hemodialysis (HD) patients during a 4-h HD session. The aim of the present study was to investigate the beneficial effect of hyperinsulinemia during HD on bioactive IGF-I and inflammatory biomarkers.
  
  
  METHODS
  In a randomized cross-over study, 11 non-diabetic HD patients received a standardised HD session with either: 1) no treatment, 2) glucose infusion (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (10% glucose added 30 IU NovoRapid® per litre, 2.5 mL/kg/h). Each experiment consisted of three periods: pre-HD (-120 to 0 min), HD (0 to 240 min), and post-HD (240 to 360 min). A meal was served at baseline (-120 min); infusions were administered from baseline to 240 min. The primary outcome was change in bioactive IGF-I during the experiment. Secondary outcomes were changes in high-sensitivity C-reactive protein, interleukin-1β, interleukin-6, and tumor necrosis factor α. Comparisons were performed using mixed-model analysis of variance for repeated measures.
  
  
  RESULTS
  From baseline to the end of study, no significant differences were observed in the changes in either serum bioactive IGF-I or total IGF-I between study days. Overall, serum bioactive IGF-I levels rose above baseline at 120 to 300 min with a maximum increase of 20% at 120 min (95% confidence interval (CI), 9 to 31%; p < 0.001), whereas total IGF-I levels rose above baseline at 180 to 300 min with a maximum increase of 5% at 240 min (95% CI, 2 to 9%; p = 0.004). A significant difference was observed in the changes in serum IGF-binding protein-1 (IGFBP-1) between study days (p = 0.008), but differences were only significant in the post-HD period. From baseline to the end of HD, no significant difference was observed in the changes in serum IGFBP-1 levels between study days, and in this time period overall serum IGFBP-1 levels were below baseline at all time points with a maximum decrease of 51% at 180 min (95% CI, 45 to 57%; p < 0.001). None of the investigated inflammatory biomarkers showed any differences in the changes over time between study days.
  
  
  CONCLUSIONS
  Postprandial insulin secretion stimulated the IGF-system during HD with no further effect of adding glucose or glucose-insulin infusion. Hyperinsulinemia during HD had no effect on biomarkers of inflammation.
  
  
  BACKGROUND
  ClinicalTrials.gov registry: NCT01209403.
authors.forename: Mark
authors.initials: M
authors.lastname: Reinhard
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Per
authors.initials: P
authors.lastname: Ivarsen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000139:chemically induced; D018836:Inflammation Mediators / Q000097:blood*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000639:trends*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005947:Glucose
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