High-dose insulin therapy reduces postoperative liver dysfunction and complications in liver resection patients through reduced apoptosis and altered inflammation.
BACKGROUND
An exaggerated inflammatory response in patients undergoing major liver resection coupled with poor nutrition diminishes liver regenerative capacity and increases the risk of postoperative complications.


OBJECTIVE
Our objective was to evaluate the biological context leading to better clinical outcomes in patients undergoing liver resection coupled with hyperinsulinemic-normoglycemic clamp vs. standard care (insulin sliding care).


METHODS
This study was a fundamental research analysis of a patient subset from a randomized-controlled study at the McGill University Health Center.


METHODS
Thirty consenting patients participating in a randomized clinical trial for liver resection received either hyperinsulinemic-normoglycemic clamp technique with 24-h preoperative carbohydrate load (intervention) or standard glucose control through insulin sliding scale treatment (control).


METHODS
Liver biopsies and plasma samples were taken at various time points before and after surgery. Primary measures included mRNA quantitation for genes related to insulin signaling, inflammation, and proliferation; proinflammatory cytokines at various time points; and liver function markers. These measurements were associated with clinical outcomes.


RESULTS
The hyperinsulinemic-normoglycemic clamp technique reduced postoperative liver dysfunction, infections, and complications. Markers of energy stores indicated higher substrate availability. Cytokine expression pattern was altered (TNF-α, IL-8, monocyte chemoattractant protein-1, IL-6, IL-10, and C-reactive protein). Apoptosis was markedly reduced, whereas the complement system was unaltered.


CONCLUSIONS
The hyperinsulinemic-normoglycemic clamp technique reduced postoperative negative outcomes by suppressing apoptosis. This phenomenon appears to be linked with higher substrate availability and altered cytokine secretion profile and may provide a long-term benefit of this therapy on liver resection patients.
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Universite Laval, Quebec, Canada.
Alexandre
A
Fisette
Mazen
M
Hassanain
Peter
P
Metrakos
Suhail A R
SA
Doi
Ayat
A
Salman
Thomas
T
Schricker
Ralph
R
Lattermann
Linda
L
Wykes
Evan
E
Nitschmann
Jessica
J
Smith
Katherine
K
Cianflone
D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015309:Glucose Clamp Technique; D006498:Hepatectomy / Q000009:adverse effects; D006505:Hepatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D008107:Liver Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D059039:Standard of Care
D007328:Insulin