SAT-615 Acute Liver Injury Impairing Ketogenesis and Insulin Clearance in a Type 1 Diabetic with Recurrent Hypoglycemia

Abstract Disclosure: G.I. Sydney: None. Background: Hypoglycemia is a potentially life-threatening complication commonly observed in individuals with diabetes, often triggered by medication, malnutrition, critical illness, or organ dysfunction. The liver plays a central role in glucose homeostasis, insulin clearance, and ketogenesis. Acute liver dysfunction can disrupt these critical pathways, resulting in significant metabolic disturbances. While impaired ketogenesis is uncommon, it can arise in the context of hepatic impairment, leading to complex pathophysiological presentations.Clinical Presentation: A 57-year-old male with a longstanding history of Type 1 Diabetes Mellitus (T1D; GAD65+, C-peptide 0.2 ng/mL; reference range: 1.1 - 4.4 ng/mL), chronic kidney disease (CKD), heart failure with reduced ejection fraction (HFrEF), and polymicrobial osteomyelitis was admitted for septic shock due to MRSA bacteremia. Hospitalization was complicated by hepatic injury, evidenced by significant transaminitis and synthetic dysfunction, thought to be secondary to congestive hepatopathy. Despite reductions in his insulin regimen, including a decrease in insulin glargine to 1 unit daily, the patient experienced recurrent episodes of severe hypoglycemia, prompting consultation with the endocrine service. Hypoglycemia was attributed to a combination of malnutrition, resulting in depleted glycogen stores, and impaired hepatic function affecting glucose homeostasis and insulin clearance. Insulin administration was withheld due to the severity of hypoglycemia despite continuous dextrose administration, and the patient was closely monitored for ketoacidosis. Remarkably, only after more than 24 hours from the last insulin dose administration did blood glucose levels begin to rise, peaking at 300 mg/dL before rapidly declining upon dextrose discontinuation, without requiring insulin. Notably, beta-hydroxybutyrate levels remained within normal limits, even in the absence of circulating insulin to act as an antilipolytic agent. These findings suggest impaired ketogenesis, despite a lack of circulating insulin, hyperglycemia and a history of diabetic ketoacidosis (DKA) just months prior to presentation. Conclusion: This case underscores the critical role of hepatic function in glucose homeostasis. The striking absence of ketosis, despite hyperglycemia and insulin discontinuation, highlights a unique presentation of impaired ketogenesis due to acute liver injury. Further research is warranted to better understand the interplay between liver dysfunction, glycemic control and ketogenesis in T1D, guiding the development of evidence-based strategies for these complex cases. Presentation: Saturday, July 12, 2025