Insulin resistance spawns hypertriglyceridemia-induced acute pancreatitis and diabetic ketoacidosis: an evolving metabolic cascade.

Insulin resistance (IR) is associated with uncontrolled lipolysis, leading to the release of free fatty acids, ectopic fat accumulation, and hypertriglyceridemia (HTG). Adipose IR is the primary factor contributing to severe HTG, which interacts with deregulated hepatic IR (Hep-IR), resulting in hypertriglyceridemic acute pancreatitis (HTGAP) and diabetic ketoacidosis (DKA). This differs from the traditional concept of 'metabolic syndrome', and demonstrates a developing metabolic cascade triggered by adipose IR that fosters pathological changes, creating a self-perpetuating cycle and establishing a two-way feedback loop with Hep-IR. This loop leads to lipotoxicity, causing self-hydrolysis of the pancreas and ultimately resulting in HTGAP. Severe HTG and HTGAP prompt the release of counter-regulatory hormones that exacerbate hyperglycemia and lipolysis, initiating a downward spiral from HTGAP to DKA.