Metabolic and cellular effects of carbohydrate-based preconditioning drinks

This thesis investigates the metabolic and cellular effects of carbohydrate-based preconditioning drinks in humans. Previous studies have demonstrated that preoperative carbohydrate loading, as opposed to overnight fasting, attenuated the development of postoperative insulin resistance by up to 50% and led to clinical benefits. Preconditioning with carbohydrate-based drinks was incorporated into enhanced recovery after surgery programs. The latter included interventions that aimed to minimise ‘metabolic-stress’ and hasten recovery after major surgery. However, the cellular mechanisms underlying the adverse effects of preoperative fasting and the beneficial effects of preconditioning with carbohydrate-based drinks were hitherto unknown. In healthy volunteers, short-term fasting (up to 24 hours) reduced liver volume, depleted liver glycogen (-50%) and lipid reserves, and increased intramyocellular lipid concentrations (+23%), as measured by magnetic resonance spectroscopy. Changes in liver glycogen were partially reversed following ingestion of a carbohydrate-based drink that also contained glutamine and antioxidants (ONS, Fresenius Kabi, Germany). Fasting also led to significantly decreased blood mononuclear cell mitochondrial complex activity. In patients undergoing laparoscopic cholecystectomy, preoperative conditioning with ONS, compared to ingestion of a placebo-drink, significantly increased intraoperative liver glycogen by 50%, increased intraoperative plasma glutamine and antioxidant concentrations, led to lower expression of skeletal muscle pyruvate dehydrogenase kinase 4 mRNA and protein expression, and finally, reduced cellular oxidative stress, as indicated by a 1.5-fold lower expression of metallothionein-1A in the ONS group. Ingestion of ONS led to markedly differing hormonal and metabolic responses compared to those following a clear carbohydrate drink (preOp®, Nutricia Clinical Care, UK), with ‘blunted’ postprandial glucose and insulin responses following ONS. Supplementing preOp® with glutamine ‘blunted’ postprandial insulin and glucose responses but this was not due to differences in glucagon-like peptide-1 concentrations. Finally, the gastric emptying of these drinks was more dependent on carbohydrate content than macronutrient composition or osmolality.EThOS - Electronic Theses Online ServiceGBUnited Kingdo