Insulin resistance spawns hypertriglyceridemia-induced acute pancreatitis and diabetic ketoacidosis: an evolving metabolic cascade
Recommended Citation
Wu C, Tiwari A, Zlatopolsky M, Qaqish O, Harder WE, Blaceri S, Saad C, Kambhatla S, and Kondur A. Insulin resistance spawns hypertriglyceridemia-induced acute pancreatitis and diabetic ketoacidosis: an evolving metabolic cascade. Cardiovasc Endocrinol Metab 2025;14(4):e00349.
Document Type
Article
Publication Date
12-1-2025
Publication Title
Cardiovasc Endocrinol Metab
Keywords
diabetic ketoacidosis; hypertriglyceridemia; hypertriglyceridemic acute pancreatitis; insulin resistance; lipolysis; type 2 diabetes
Abstract
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.
PubMed ID
41281883
Volume
14
Issue
4
First Page
00349
Last Page
00349
