SAT-276 Time Course Of Triglyceride Reduction During IV Insulin Therapy As A Clue To Underlying Genetic Dyslipidemia

Abstract Disclosure: S.I. Suarez: None. S.K. Majumdar: None. Severe hypertriglyceridemia, defined as triglyceride (TG) levels over 1000 mg/dL can result in pancreatitis and is often treated with nothing by mouth status (NPO) and IV insulin. This typically results in a 40% decline in TG’s during the first 48 hours (1), and TG levels < 1000 mg/dL in less than 3 days for most patients (2). A particularly delayed response in TG lowering may provide a clue to a previously undiagnosed genetic dyslipidemia. We present two patients with severe hypertriglyceridemia who demonstrated delayed triglyceride clearance during nutrient restriction and IV insulin therapy who harbored genetic variants in the ApoE and LPL genes. The first patient was a 52-year-old woman with hypertension and hypothyroidism, who presented with several months of weakness, polydipsia, polyuria, and unintentional weight loss. Initial workup revealed a blood sugar of >400 mg/dL and a hemoglobin A1C of 17.8%, TSH 6.2 (0.27-4.2 uIU/mL), Free T4 1.09 (0.8-1.50 ng/dL). She was found to have a TG level of 3,342 mg/dL. She was admitted to the intensive care unit (ICU) for diabetic ketoacidosis and severe hypertriglyceridemia. She was kept NPO and started on IV insulin for nearly 7 days since her TG’s declined very slowly: 2,942, 1,991, 1,939, taking approximately 160 hours to reach levels of <1000, then down only to 643 (all in mg/dL) at discharge eight days later. During her outpatient follow-up, Cushing’s Disease workup was negative, but lipoprotein electrophoresis revealed type III or familial dysbetalipoproteinemia, and she was found to be homozygous for Apo E2 gene (APO E2/E2). The second patient was a 53-year-old man with history of hypertriglyceridemia since childhood, prediabetes, coronary artery disease, and hypertension, who presented to the hospital because of abdominal pain. He had been off lipid lowering therapy for several months due to depression. His initial triglyceride levels were 4,214 mg/dL and TSH was 0.785 uIU/mL. He was placed on IV insulin and kept NPO for approximately 100 hours when TG levels went below 1000 mg/dL, being 846 mg/dL at that time. TSH was 0.785 uIU/mL. After resuming food intake, TG’s remained elevated at discharge (1,086 mg/dL). Genetic evaluation revealed a heterozygous variant in the LPL gene: LPL:NM_000237:exon5:c.G644A:p.G215E (hg19 chr8:19811733). Plotting clearance over time during IV insulin therapy and NPO status for both patients revealed a linear decline in TG levels R2 = 0.67, Y = -14.5*X + 2739, where Y = TG in mg/dL and X = number of hours from initial TG. TG lowering to levels < 1000 mg/dL was much slower than reported in unselected patients with similar initial levels (2). These cases highlight the value of monitoring TG kinetics, suggesting that poor TG clearance during standard therapy should prompt consideration of genetic dyslipidemia. Early identification impacts management, prevention of recurrence, and family counseling. Presentation: Saturday, July 12, 2025