Preoperative Protein or Methionine Restriction Preserves Wound Healing and Reduces Hyperglycemia

Dietary restriction (DR), defined as reduced nutrient intake without malnutrition, is associated with longevity extension, improved glucose metabolism, and increased stress resistance, but also poor wound healing. Short-term preoperative DR followed by a return to normal feeding after surgery results in improved surgical outcomes in preclinical models. However, the effect of preoperative DR on wound healing and perioperative glucose homeostasis is currently unknown. Here, we tested the effects of two different preoperative DR regimens—protein restriction (PR) and methionine restriction (MR)—on wound healing and perioperative glucose homeostasis using an established murine model of wound healing in both nondiabetic and diabetic mice. Surgical outcomes were tested using the McFarlane flap in nondiabetic and streptozotocin-induced diabetic mice. Short-term dietary preconditioning included 1 wk of PR or MR diet (1-2 wk) versus an isocaloric complete diet before surgery; all mice were returned to a complete diet postoperatively. Outcome measures of flap wound recovery included skin viability and laser Doppler imaging of flap perfusion and assessment of CD45+ cell infiltration. Glucose homeostasis was assessed by glucose tolerance testing and by perioperative glucose levels in the diabetic cohort. No significant differences were observed in percentage of viable skin, perfusion, or immune cell infiltration at 7-10 d after surgery in PR or MR mice compared with controls in healthy or diabetic mice. Preoperative glucose tolerance and postoperative glucose levels were however significantly improved by both PR and MR in diabetic mice. Short-term dietary preconditioning with PR or MR did not impair wound healing in nondiabetic or diabetic mice. However, both regimens reduced preoperative hyperglycemia in diabetic mice. Thus, brief preoperative dietary manipulations stand as strategies to potentially improve perioperative hyperglycemia with no deleterious effects on wound healing in mice.