INS and Hyperglycemia: Beyond the evidence for the dysregulation of glucose processing pathways that occur during ESHP in the context of high glucose and insulin levels, there is an abundance of evidence to suggest that acutely high glucose and insulin levels themselves are associated with induction or exacerbation of oxidative stress (42–44) Acute hyperglycemia and high insulin occurring during critical illness causes damage to various cellular structures, including mitochondria, leading to redox imbalances inside the cell.