Insulin is central, plasmapheresis is salvage: clinical spectrum and management of severe hypertriglyceridemia in 21 children with diabetic ketoacidosis

Background: Severe hypertriglyceridemia (SHTG), characterized by plasma triglycerides (TG)>11.3 mmol/L is a rare but serious complication in children who develop diabetic ketoacidosis (DKA). However, the current body of evidence is predominantly composed of case reports, highlighting a substantial gap in both the understanding and management of this condition. Methods: This was a retrospective electronic medical record review of pediatric patients with DKA complicated by SHTG who were referred to the Beijing Children's Hospital over a 10-year period. Results: A total of 21 pediatric patients with DKA complicated by SHTG were identified, with a male-to-female ratio of 8:13. The median age at diagnosis was 11.3 years [interquartile range (IQR) 10.5-13.2, range 2.0-17.4], with approximately 76.2% (16/21) of patients aged ≥10 years. Among these patients, 10 were diagnosed with type 1 diabetes mellitus, 5 with type 2 diabetes mellitus, and 6 with unclassified diabetes mellitus. 17 patients were newly diagnosed with diabetes, whereas 4 had a history of pre-existing diabetes. Notably, 3 of these 4 patients had discontinued insulin prior to admission. In terms of complications, 7 patients had acute pancreatitis. Regarding treatment, all patients received insulin therapy, among whom 7 patients were treated with plasmapheresis. Compared with insulin therapy alone, the plasmapheresis group showed a shorter median time to achieve the TG level <5.6 mmol/L, though this finding should be interpreted cautiously due to potential selection bias. Among the 7 patients who received plasmapheresis, 4 developed venous thrombosis. During follow-up, patients who underwent plasmapheresis maintained stable lipid profiles and achieved complete resolution of thrombosis. Conclusion: We present the largest single-center experience on SHTG in pediatric patients with DKA, with a particular focus on plasmapheresis. We recommend early assessment of dyslipidemia and pancreatic enzymes in patients with DKA. Insulin therapy remains the cornerstone of management. However, in children who show unsatisfactory reduction in triglyceride levels or persistent abdominal pain despite insulin treatment, prompt initiation of plasma exchange may be considered as a rescue therapy to rapidly lower TG levels, which could potentially mitigate the risk of developing or worsening acute pancreatitis. This hypothesis requires validation in larger prospective studies.