TNF‐a–mediated hyperglycemia in Obese Zucker rats following orthopedic trauma

Abstract

Obese patients with orthopedic trauma exhibit increased inflammation and complications correlated with high glucose levels. We hypothesize that in obesity there is increase risk of trauma‐induced hyperglycemia due to insulin resistance and inflammation. Fasted lean (LZ) and obese Zucker (OZ) rats were treated with vehicle or etanercept, a TNF‐α inhibitor (2mg/kg, ip.). One hour after the treatment, orthopedic trauma was mimicked by soft tissue injury followed by an injection of bone components into bilateral hindlimbs. Glucose levels were measured for 6 hours following trauma. Under control conditions, OZ exhibited similar basal fasting glucose levels but impaired glucose tolerance (OGTT) as compared with LZ. Etanercept treatment had no effect on the OGTT in LZ or OZ. After trauma, the glucose levels in LZ were moderately increased within 10 minutes and decreased to basal levels after 6 hours (Figure). However, OZ exhibited a severe hyperglycemia as compared with LZ during the 6 hours of recovery after trauma. Etanercept treatment markedly improved the trauma‐induced hyperglycemia in OZ with no effect in LZ. These results suggest an exacerbated trauma‐induced hyperglycemia in obesity due to TNF‐α‐dependent mechanisms. Supported by AHA‐12SDG12050525, NIH HL‐51971, and HL‐89581