Route of nutritional support affects metabolic outcomes in an endotoxemia model of sepsis

Learning Objectives: Sepsis is common in critically ill patients and the development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Critically ill patients receive nutritional support in intravenous dextrose infusions and in enteral tube feeds but the effects of these interventions on metabolic function in sepsis are unknown. Methods: 10 week old C57/BL6 mice (n=64) were randomized to (1) surgical implantation of either gastric cannula for enteral or venous catheter for parenteral infusions, (2) lipopolysaccharide (LPS) challenge (1mg/kg) or vehicle, and (3) saline (100uL/ hr) or dextrose infusion (equivalent to 10% daily caloric needs) immediately following septic insult. Frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed five hours after LPS to assess metabolic function. Results: Control (vehicle) mice receiving saline by either enteral or parenteral routes exhibited normal glucose disposal and insulin response with return to baseline in 20 minutes during FSIVGTT. Mice in saline-LPS groups demonstrated mild hypoglycemia prior to and higher peak insulin secretion during FSIVGTT but similar glucose tolerance compared to controls. Mice in vehicle-dextrose groups, by both enteral and parenteral routes, also maintained normal glucose tolerance. Mice receiving parenteral dextrose and LPS demonstrated profound glucose intolerance with blood sugars reaching over 600 mg/ dL, inappropriately low insulin secretion, and marked insulin resistance during FSIVGTT. In contrast, mice receiving enteral dextrose and LPS demonstrated normal glucose disposal and insulin secretion similar to control mice. Conclusions: While parenteral dextrose induces severe metabolic dysfunction in endotoxemic mice, enteral dextrose administration does not compromise glucose disposal or insulin secretion. Further studies will determine the role of gut derived insulin secreting and sensitizing hormones in mediating improved glycemic control.