Acute pancreatic beta cell apoptosis by IL-1β is responsible for postburn hyperglycemia: Evidence from humans and mice.

BACKGROUND: Acute hyperglycemia is regarded as a risk factor for critically ill patients; however, insufficient understanding of its nature and underlying mechanisms hinders widespread adoption of glycemic control in critical care units.

METHODS: A single center, prospective cohort study recruiting 107 burn patients and 62 controls was conducted to characterize the early phase of acute hyperglycemia in burn patients. A total of 1643 blood samples were collected and analyzed over the entire postburn 200 h. A mouse severe burn model was used to study the underlying mechanisms of acute hyperglycemia postburn.

RESULTS: The dynamic change of postburn blood glucose represented a distinctive pattern in amplitude and duration that was in parallel with the degree of burn injury. Multiple linear regressions revealed that serum insulin, glucagon and glucocorticoid were the major factors affecting blood glucose postburn. Particularly, extensive burns impaired capacity and responsiveness of pancreatic insulin secretion, which was associated with increased serum IL-1β in burn patients. Mechanistically, acute IL-1β elevation specifically induced pancreatic beta cell apoptosis and dampened capacity of insulin secretion, leading to postburn hyperglycemia in burned mice. More importantly, inhibition of IL-1β not only alleviated pancreatic beta cell apoptosis, but also attenuated hyperglycemia and improved survival of burned mice.

CONCLUSIONS: Our findings reveal a novel mechanism of acute hyperglycemia postburn in which impaired insulin secretory capacity mediated by IL-1β leads to acute hyperglycemia. These data suggest that targeting IL-1β to restore endogenous insulin secretory function may be a novel glycemic control strategy to improve outcomes for burn patients.