Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study

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

Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

“…Bioactive IGF1 was determined by the KIRA assay based on human embryonic renal cells (EBNA 293) transfected with the human IGF1R gene (21), with modifications as previously published (24). Total serum IGF1 was determined by time-resolved immunofluorometric assay with modifications as recently published (24). Before assaying, serum was separated by gel chromatography at pH 2.7 in a semi-automated setup.…”

“…Both IGF1 assays were using the international IGF1 standard (WHO 02/254) as a calibrator (obtained from the National Institute for Biological Standards and Control (NIBSC), Hertfordshire, UK). IGF-binding protein 1 (IGFBP1) was measured by an in-house assay developed and validated by our laboratory (25), as described previously (24).…”

GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

“…A total of 20 normal-weight subjects (meanGS.E.M., BMI: 25G2) comprising ten 'young' subjects (5F/5M) with a mean (range) age of 25 (20)(21)(22)(23)(24)(25)(26)(27)(28) years and ten 'old' subjects (5F/5M) with a mean age of 65 (60-72) years participated in this study. None were smokers or receiving prescribed drugs, and none of the females received estrogen supplementation.…”

Short-term effects of NPH insulin, insulin detemir, and insulin glargine on the GH–IGF1–IGFBP axis in patients with type 1 diabetes

“…Limits of detection for total IGF1, IGFBP3, and GH were 4.4, 50, and 0.015 mg/l respectively. Bioactive IGF was determined by an IGF1 receptor (IGF1R) kinase receptor activation (KIRA) assay as described previously (17) with modifications (18). Briefly, this assay determines the ability of serum IGFs to activate (i.e.…”

“…The KIRA assay has a detection limit of !0.08 mg/l, and intra-and inter-assay CV values of !7 and !15% respectively. IGFBP1 was determined by an in-house time-resolved immunofluorometric assay (TR-IFMA) (18). The intra-assay CV value of samples assayed in duplicates averaged !5%, and the inter-assay CV value of an internal control (IGFBP1 standard) and a control serum sample averaged 8.1 and 7.0% respectively.…”