Regulation of Insulin and Insulin-Like Activity in Malnourished Patients with Carcinoma Ventriculi Subjected to Total Gastrectomy and Personalized Nutritional Support

J Med Biochem. 2016 Jan;35(1):17-25. doi: 10.1515/jomb-2015-0013. Epub 2015 Dec 30.

Abstract

Background: Insulin and insulin-like growth factor (IGF) activities are disturbed during critical illness. Time-course changes in the concentrations of insulin, IGF-I and IGF-binding proteins (IGFBPs) were monitored in this study and their correlation with interleukin (IL)-6 was assessed in patients subjected to total gastrectomy and specific nutritional regime.

Methods: Patients were fed post-operatively according to the following scheme: parenteral nutrition on day 1, enteral nutrition combined with parenteral form from day 2 to 7, peroral nutrition from day 8 and full oral nutrition from day 14. Blood samples were taken periodically and the levels of IL-6, insulin, IGF-I and IGFBP-1 to -4 were determined.

Results: On day 1 post-operatively, the concentration of IL-6 reached its maximum and decreased afterwards. The concentration of insulin increased until day 3 and then started to fall. The concentration of IGF-I, already low preoperatively, continued to decrease. The concentration of IGFBP-1 peaked on day 1 post-operatively, whereas the concentration of IGFBP-3 decreased on that day. The concentration of IL-6 correlated positively with the concentration of IGFBP-1 and negatively with IGFBP-3. On day 14, the concentrations of IL-6, insulin and IGFBP-1 returned to or were close to their basal levels, whereas the concentrations of IGF-I and IGFBP-3 remained reduced.

Conclusions: A 14-day post-operative recovery, which included specific nutritional support, was suitable to restore insulin concentration and re-establish IGFBP-1 regulation primarily by nutrition. Very low IGF-I level on day 14 after surgery and IGFBP-3 concentration still lower than before surgery indicated that the catabolic condition was not compensated.

Uvod: Aktivnost insulina i faktora rasta sličnih insulinu (IGF) izmenjena je u kritičnom stanju. U ovoj studiji je praćena promena koncentracije insulina, IGF-I, IGF vezujućih proteina (IGFBP) i utvrđivana njihova korelacija sa interleukinom (IL)-6 kod pacijenata sa tumorom želuca, koji su podvrgnuti totalnoj gastrektomiji i specifičnom režimu ishrane.

Metode: Pacijenti su postoperativno hranjeni prema sledećem režimu: parenteralna ishrana prvog dana, enteralna ishrana u kombinaciji sa parenteralnom od drugog do sedmog dana, peroralna ishrana osmog dana i redovna ishrana četrnaestog dana. Periodično su uzimani uzorci krvi i određivane koncentracije IL-6, insulina, IGF-I i IGFBP-1 do -4.

Rezultati: Koncentracija IL-6 je dostigla maksimum prvog dana nakon operacije i dalje je opadala. Koncentracija insulina je rasla do trećeg dana, a zatim je počela da pada. Koncentracija IGF-I, koja je bila niska pre operacije, nastavila je da opada. Prvog dana posle operacije, koncen-tracija IGFBP-1 je porasla, dok se koncentracija IGFBP-3 smanjila. Promene IGFBP-1 i IGFBP-3 su bile izraženije sa većim skokom IL-6. Četrnaestog dana su se koncentracije IL-6, insulina i IGFBP-1 vratile ka referentnim vrednostima, dok su koncentracije IGF-I i IGFBP-3 ostale smanjene.

Zaključak: Četrnaestodnevni postoperativni oporavak, koji je obuhvatao specifičan režim ishrane, pokazao se odgova-rajućim za uspostavljanje kontrole koncentracije insulina i IGFBP-1. Sa druge strane, vrlo niska koncentracija IGF-I, kao i koncentracija IGFBP-3 ispod preoperativne vrednosti, ukazuju na to da katabolički stres kod ovih pacijenata i dalje nije kompenzovan.

Keywords: enteral nutrition; insulin; insulin-like growth factor I; insulin-like growth factor binding proteins; interleukin 6; total gastrectomy.