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Alexandre Fisette, Mazen Hassanain, Peter Metrakos, Suhail A. R. Doi, Ayat Salman, Thomas Schricker, Ralph Lattermann, Linda Wykes, Evan Nitschmann, Jessica Smith, Katherine Cianflone, High-Dose Insulin Therapy Reduces Postoperative Liver Dysfunction and Complications in Liver Resection Patients through Reduced Apoptosis and Altered Inflammation, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 1, 1 January 2012, Pages 217–226, https://doi.org/10.1210/jc.2011-1598
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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.
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).
This study was a fundamental research analysis of a patient subset from a randomized-controlled study at the McGill University Health Center.
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).
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.
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.
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.
