High-Dose Insulin Therapy Reduces Postoperative Liver Dysfunction and Complications in Liver Resection Patients through Reduced Apoptosis and Altered Inflammation.
Author(s): Fisette A, Hassanain M, Metrakos P, Doi SA, Salman A, Schricker T, Lattermann R, Wykes L, Nitschmann E, Smith J, Cianflone K
Affiliation(s): Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec (A.F., J.S., K.C.), Faculte de Medecine, Universite Laval, Quebec, Canada G1V 4G5; Section of Hepatopancreatobiliary Surgery (M.H., P.M.), Department of Anaesthesia (T.S., R.L.), and School of Dietetic and Human Nutrition (L.W., E.N.), McGill University Health Center, Montreal, Canada H3G 1A4; Department of Surgery (M.H., P.M., A.S.), College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia; and Clinical Epidemiology Unit (S.A.R.D.), School of Population Health, University of Queensland, Brisbane, Queensland 4072, Australia.
Publication date & source: 2011-10-26, J Clin Endocrinol Metab., [Epub ahead of print]
Context: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.Objectives: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).Design and Setting:This study was a fundamental research analysis of a patient subset from a randomized-controlled study at the McGill University Health Center.Patients and Intervention: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).Main Outcome Measures: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-alpha, IL-8, monocyte chemoattractant protein-1, IL-6, IL-10, and C-reactive protein). Apoptosis was markedly reduced, whereas the complement system was unaltered.Conclusion: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.