Abstract
BackgroundA 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.MethodsIn 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.ResultsFrom 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.ConclusionsPostprandial 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.Trial registrationClinicalTrials.gov registry: NCT01209403
Highlights
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
Mean blood glucose levels (BG) levels were comparable at baseline (NT: 5.3 ± 0.4; G: 5.1 ± 0.5; glucose-insulin infusion (GI): 5.1 ± 0.4 mmol/L, p = 0.13), but a significant difference in the changes over time were observed between study days (p < 0.001)
BG levels were higher on G (p < 0.001) and GI (p = 0.02) study days compared with no treatment (NT) study days
Summary
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. Causes of PEW in maintenance HD patients include reduced intake of energy and protein, resistance to the actions of anabolic hormones such as insulin, growth hormone (GH), and insulin-like growth factor-I (IGF-I) [2,3,4,5], and non-specific inflammatory processes [6,7,8,9]. HD per se stimulates muscle and whole body protein loss which further increases the risk of PEW [10,11,12]. Amino acid kinetic studies have demonstrated that HD in the postabsorptive state induces muscle protein loss by increased muscle protein breakdown [13]. There is a positive correlation between interleukin-6 (IL-6) levels and muscle protein breakdown, and as IL-6 levels peak after completion of the HD procedure a considerable protein catabolic “carry-over effect” may extend to the post-HD period [16]
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