MON-583 Lipoprotein-X-Associated Severe Peripheral Insulin Resistance Secondary to Biliary Sclerosis Treated with Plasmapheresis

Abstract Disclosure: H. Abdelrahman: None. M. Connelly: employee of and hold stock in Labcorp.. G. Westcott: None. S. Brown: None. E. Yunasan: None. Z. Taxin: None. Lipoprotein(X) is an abnormal lipoprotein formed in cholestatic disease when biliary contents leak into the plasma. Here, we present a case of LpX with severe insulin resistance which has not been previously reported. A 28-year-old woman with progressive liver failure and dyslipidemia was admitted to the hospital for liver transplant evaluation. She was hospitalized for gallstone pancreatitis complicated by diabetic ketoacidosis (A1c 12%) one year prior. MRCP demonstrated intrahepatic biliary ductal dilation; liver biopsy demonstrated a sclerosing pattern. Autoimmune hepatic serologies were negative. She had immigrated from El Salvador three years prior. The diabetes service was consulted due to high insulin requirements (3.1 u/kg/d) with uncontrolled hyperglycemia (BG 402 mg/dL; c-peptide 2.45 ng/mL). Labs on presentation were notable for cholesterol 1802 mg/dL, triglycerides 420 mg/dL, HDL <3 mg/dL, and directly measured LDL 131 mg/dL. She weighed 38 kilograms and had scattered xanthomata. The presence of LpX was confirmed by NMR spectroscopy and gel electrophoresis with Filipin staining. Her peak TDD of insulin was 263 units on U-100 before transitioning to U-500 insulin, when she had a daily insulin requirement up to 6 u/kg/d. Due to elevated serum viscosity (2.9 cP; reference: 1.4-1.8 cP) and concern for hyperviscosity syndrome with a recent nosebleed, she underwent plasma exchange. Her insulin sensitivity improved linearly with decreased lipemia, with decreased TDD (∼120 units) on U-100 insulin. The calculated HOMA-IR 6.6 (insulin level 8 µIU/mL corresponding to BG 333 mg/dL) was consistent with persistent insulin resistance. LpX consists of a phospholipid shell (65%), free (unesterified) cholesterol (25%) and an albumin core. Since LpX lacks apolipoprotein B, therapies that increase LDL receptor density such as statins or PCSK9 inhibitors are ineffective. While liver transplantation is the definitive treatment, plasma exchange is a temporizing measure. Our patient required modification of her insulin doses after plasma exchange due to improved insulin sensitivity following clearance of the abnormal lipid fraction. The etiology of her diabetes in this case was due to pancreatic damage (relatively low C-peptide and HOMA-beta 10.6%) and peripheral insulin resistance due to lipotoxicity. This case represents a novel model of diabetes management for this rare condition not previously reported in the literature. Presentation: Monday, July 14, 2025