Abstract Disclosure: E.R. Perez Roman: None. D.A. Lopez Rodriguez: None. K. Ramirez Gorbea: None. M. Sanchez Cordero: None. Y. Garcia Cruz: None. Acute pancreatitis is an acute inflammatory process of the pancreas that if left untreated can become complicated resulting in multiple organ damage and a fatal outcome in approximately 10%-40% of patients. There are well-known causes that can lead to pancreatitis such as alcohol, hereditary disorders, cholelithiasis, prior pancreatitis, and medications. Less frequently, it can be related to poorly controlled diabetes mellitus and diabetic ketoacidosis (DKA), given that in a state of low or deprived insulin, there is a breakdown of triglycerides into toxic fatty acids by pancreatic lipases; this lipotoxicity can result in the development of acute pancreatitis. We present a case of a 50-year-old woman with a past medical history of untreated hyperlipidemia and previous pancreatitis who was transferred to our institution with acute epigastric pain radiating to the back, nausea, and persistent vomiting. Upon arrival, blood glucose was 299 mg/dL, HbgA1c of 11.4%, lactic acid of 3.6 mmol/L, hypocalcemia of 6.0 mg/dl, hypoalbuminemia, and elevated pancreatic enzymes, amylase 869 U/L and lipase 2,493 U/L. The lipid panel was remarkable for total cholesterol of 1,085 mg/dL and triglycerides of 4,369mg/dL. Abdominopelvic CT scan confirmed acute pancreatitis with extensive peripancreatic and regional mesenteric edema. This patient was treated with aggressive IV fluid resuscitation and treated for DKA as per protocol. Despite prompt treatment, the patient rapidly deteriorated, developing pulmonary effusions and impending respiratory failure requiring mechanical ventilation. Her hyperglycemia was challenging to control and in the setting of severe hypertriglyceridemia, insulin requirements were higher, as intravenous insulin is useful in patients with concomitant findings, in the absence of plasmapheresis availability. Despite the marked reduction of triglyceride to 978 mg/dL and a decrease in pancreatic enzymes, multiorgan failure developed. Unfortunately, the patient died. Repeated abdominopelvic CT imaging revealed the progression of the disease to necrotizing pancreatitis involving the pancreatic head, uncinate process, and neck of the pancreas with evidence of a small hypodense lesion at the level of the tail of the pancreas. This case emphasizes the importance of prompt recognition of acute pancreatitis secondary to uncontrolled hyperglycemia with concomitant severe hypertriglyceridemia since it can lead to a worse clinical outcome as seen in our patient who developed rapid progression to necrotizing pancreatitis. It is paramount not to delay treatment with aggressive fluid resuscitation, continuous insulin infusion, and if available, plasmapheresis; as these treatment strategies in conjunction can be life-saving. Presentation: 6/3/2024