Perioperative nutrition and insulin resistance

Surgical trauma induces a catabolic response with development of insulin resistance as a central and wellcharacterised feature. In insulin resistance, the stimulating effect of insulin on peripheral glucose uptake and the suppressing effect of insulin on endogenous glucose release are decreased, resulting in hyperglycaemia. It is marked the first day after surgery and normalises within two to three weeks. Preoperative treatment with oral carbohydrates instead of traditional fasting and use of epidural anaesthesia reduce postoperative insulin resistance. Both starvation and bed rest are known to induce insulin resistance. In the first study, the effect of traditional post-surgical low caloric feeding and bed rest on insulin sensitivity (hyperinsulinaemic (0.8 mU/kg/min) normoglycaemic (4.5 mM) clamps) and substrate utilisation (indirect calorimetry) were studied in healthy volunteers in a control situation and after three days of low caloric feeding and bed rest. Half of the volunteers underwent a second protocol with identical low caloric feeding but without bed rest. Three days of low caloric feeding induced a decrease in insulin sensitivity by nearly 60 % and caused alterations in substrate utilisation both with and without bed rest. The metabolic effect of low caloric feeding and bed rest was not related to age in the present study. Thus, low caloric feeding might be of importance for development of postoperative insulin resistance. The use of total parenteral nutrition (TPN) in patients undergoing surgery in order to reduce catabolism has been shown to induce hyperglycaemia and increase the complication rate, mainly infectious. However, the effects of TPN have not been investigated in patients treated to proactively minimise development of postoperative insulin resistance. Insulin sensitivity, glucose kinetics (6,6H 2 -D-glucose) and substrate utilisation were studied before surgery and on the third postoperative day in 13 patients undergoing colorectal resections. Patients were randomised to postoperative hypocaloric glucose or TPN. All received preoperative oral carbohydrate treatment and epidural anaesthesia during and after surgery. Whole-body glucose disposal decreased by only approximately 25 % irrespective of whether or not TPN was given. Low caloric feeding resulted in changes in substrate utilisation and nitrogen balance resembling starvation, while TPN attenuated these changes. Preoperative oral carbohydrate treatment has been used as an evening dose the day before surgery (100 g) and a morning dose (50 g). The aim of study III was to investigate to what extent the two doses, respectively, affected insulin sensitivity at the time of onset of surgery. Insulin sensitivity and substrate utilisation were measured in six healthy volunteers on four occasions in a randomised order (in the overnight fasted state, after the evening dose only, after the morning dose only, and after both doses). Oral carbohydrate treatment given in the morning increased insulin sensitivity three hours later (corresponding to the time of onset of surgery) by approximately 50%. The evening dose did not affect insulin sensitivity the following day. Thus, increased insulin sensitivity at the onset of surgery might, at least in part, explain the positive effects of carbohydrate loading seen on postoperative insulin sensitivity. In paper IV, the effect of preoperative oral carbohydrate treatment on postoperative whole-body protein kinetics was evaluated. Insulin sensitivity, protein (H 5 -phenylalanine, H 2 -tyrosine, H 4 -tyrosine) and glucose (6,6H 2 -D-glucose) kinetics and substrate utilisation were studied before surgery and on the first postoperative day in 12 patients undergoing colorectal resections. Patients were randomised between oral carbohydrate treatment and a placebo drink before surgery. Preoperative carbohydrate treatment improved postoperative whole-body protein balance. The effect of insulin on whole-body protein kinetics was not altered after surgery.