Impact of streptozotocin-induced hyperglycemia on the host response to sepsis.
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BACKGROUND: Diabetes is a common comorbidity in patients with sepsis, yet the influence of baseline glycemic status on sepsis outcomes remains unclear. Clinical studies report conflicting associations between diabetes and sepsis mortality. OBJECTIVES: To evaluate how short-term (ie, 4-5 weeks) preinfection hyperglycemia influences the host response to sepsis using a model of fecal-induced peritonitis. METHODS: Hyperglycemia was induced in C57BL/6 mice (both sexes) via streptozotocin injections. Hyperglycemic and normoglycemic mice were subjected to fecal-induced peritonitis, with endpoints at 8 hours and 48 hours postinfection. Blood glucose, insulin, advanced glycation end-products, cytokines (interleukins 6 and 10), coagulation markers (thrombin-antithrombin and protein C), cell-free DNA (cfDNA), lung myeloperoxidase, bacterial loads, organ injury, and survival were assessed. RESULTS: Streptozotocin-treated mice exhibited low insulin and elevated blood glucose, advanced glycation end-products, thrombin-antithrombin, and cfDNA compared with normoglycemic mice. Despite these baseline differences, the trajectory of sepsis was similar in both groups. Blood glucose rapidly dropped postinfection, converging at approximately 2 mM within 12 hours in nonsurvivors and partially recovering in survivors. Plasma insulin increased in both groups in response to sepsis, returning to baseline levels by 48 hours in survivors. No significant differences were found between the groups in sepsis-related outcomes, including sepsis scores, body temperature, inflammatory and coagulation responses, cfDNA, lung myeloperoxidase, bacterial burden, organ injury, or survival. CONCLUSION: Short-term hyperglycemia did not alter the course of sepsis compared with normoglycemic mice. Blood glucose levels partially recovered in surviving mice, suggesting that restoring glucose homeostasis may improve outcomes.
