MON-658 When Metabolic Stress Meets Genetics: A Triad of DKA, Acute Pancreatitis, and Hypertriglyceridemia in a Patient with LMF1 Mutation

• Published in: Journal of the Endocrine Society Vol. 9; no. Supplement_1
• Main Authors: Khachfe, Soulaf Abou, Guillen-Lopez, Claudia, Patel, Aesha, Lonescu, Madalina
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 22.10.2025
• Subjects: Apheresis; Diabetic ketoacidosis; Insulin; Metabolism; Mortality; Mutation; Pancreatitis; Triglycerides
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvaf149.1016

Abstract Disclosure: S. Abou Khachfe: None. C. Guillen-Lopez: None. A. Patel: None. M. Lonescu: None. Introduction: The combination of diabetic ketoacidosis (DKA), severe hypertriglyceridemia (HTG), and acute pancreatitis (AP) is a rare but critical triad with mortality rates up to 80%. It presents diagnostic and management challenges, often causing metabolic disturbances, organ failure, and prolonged stays. The pathophysiology of this triad is complex, with evidence suggesting a bidirectional relationship. HTG seems to link DKA and AP, though the directionality (DKA→HTG→AP vs. HTG→AP→DKA) remains unclear. In DKA, insulin deficiency promotes lipolysis, increasing free fatty acids (FFA) and very low-density lipoprotein (VLDL) production in the liver, leading to HTG. While moderate HTG is common in DKA, severe HTG (triglycerides >1,000 mg/dL) is rare. In such cases, underlying genetic mutations should be considered. The lipase maturation factor (LMF1) gene encodes a protein essential for lipoprotein lipase (LPL) function, which breaks down triglycerides in chylomicrons and VLDL. Mutations in LMF1 disrupt this process, resulting in severe HTG. Case: A 30-year-old male with poorly controlled T2DM, HTG, and recurrent pancreatitis presented with severe abdominal pain. He had poor adherence to metformin, Jardiance, and pioglitazone, with an A1C of 10.7%. Labs showed lipase 1611 U/L, glucose 238 mg/dL, anion gap 27, beta-hydroxybutyrate 9.7 mmol/L, and triglycerides >2000 mg/dL. He was admitted and treated with IV hydration, insulin infusion, statins, and fenofibrate for euglycemic DKA and HTG-induced AP. Persistently elevated triglycerides >1000 mg/dL required two plasmapheresis sessions, leading to clinical improvement. He was discharged on insulin, atorvastatin, and fenofibrate with a diabetes education referral. Given his recurrent HTG-AP-DKA (>5 episodes), genetic testing for primary HTG was performed, revealing a heterozygous missense mutation in the LMF1 gene (c.1352G>A, p.Arg451Gln). Discussion: AP and DKA are life-threatening conditions with mortality rates reaching 80% when they coexist. Overlapping symptoms and nonspecific amylase and lipase elevations in DKA can complicate diagnosis, leading to poor outcomes. Multidisciplinary collaboration and increased physician awareness are key for optimal management. Current AP severity scoring systems, like Ranson and APACHE II, are impacted by DKA-related factors such as high glucose and low pH, making them less reliable in these cases, highlighting the need for tailored scoring systems, more effective diagnostic algorithms, and specific management protocols. Genetic screening in specific populations could identify patients at risk, enabling preventive measures and reducing the burden of severe complications. Data comparing insulin infusion and plasmapheresis for treating HTG in HTG-AP-DKA is limited. Plasmapheresis may be more effective in LPL deficiency cases, warranting further research in the future. Presentation: Monday, July 14, 2025