SUN-632 Beyond Diabetes: The Enigma of Hypoglycemia in End-Stage Renal Disease

Abstract Disclosure: Y. Velis: None. N.S. Sweis: None. J. Sanchez Perez: None. While diabetic hypoglycemia in end-stage renal disease (ESRD) is well-documented, non-diabetic hypoglycemia in this population is less commonly reported. We present a case of non-diabetic hypoglycemia in an ESRD patient, where endogenous hyperinsulinemia was suspected as the underlying cause. A 41-year-old male with history of ESRD on HD, OUD on methadone, PTSD, and hypothyroidism was admitted for suicidal ideations. On admission, he was found to be hyperkalemic and bacteremic, and his clinical course was complicated by symptomatic hypoglycemia. Point-of-care glucose measurements revealed a glucose level of 45 mg/dL (reference range: 65-110 mg/dL), which correlated with a serum glucose level of 39 mg/dL. He endorsed palpitations and diaphoresis, which resolved with the correction of hypoglycemia. Hypoglycemic episodes occurred both before and after treatment with trimethoprim/sulfamethoxazole. There was no history of bariatric surgery. Adrenal insufficiency was ruled out in light of his chronic methadone use with ACTH stimulating testing resulting in cortisol levels of 16.0 UG/DL, 21.4 UG/DL, 29.9 UG/DL at 0, 30 and 60 min, respectively. Additional workup revealed a normal HbA1c of 4.4% (<5.7%), negative insulin antibodies, and elevated biochemical markers of endogenous hyperinsulinemia: C-peptide 6.8 ng/mL (0.8-4.4 ng/mL), proinsulin 7.8 pmol/L (≤7.2 pmol/L), total insulin 13 uIU/mL (3-25 uIU/mL) and beta-hydroxybutyrate (BHB) <0.2 mmol/L (<0.4 mmol/L). Abdominal CT imaging did not reveal a pancreatic mass. The patient also reported a 40-pound weight loss over the past year and had a BMI of 18.8 kg/m². A nutrition consultation was initiated for dietary supplements. Given the concern for endogenous hyperinsulinemia, diazoxide 50 mg qhs was recommended, but the patient declined due to the medication's unpleasant taste. Hypoglycemia in this case was likely multifactorial, occurring in the context of trimethoprim/sulfamethoxazole use, sepsis, decreased endogenous insulin clearance, low glycogen reserves, and impaired gluconeogenesis due to ESRD. Additionally, the patient appears to have hyperinsulinemia, as evidenced by elevated C-peptide, proinsulin, and insulin levels, along with a low beta-hydroxybutyrate (BHB). However, reference ranges for these labs in ESRD patients without diabetes are not well established. While guidelines exist for diagnosing hypoglycemia in patients without ESRD, literature is limited regarding this diagnosis in the ESRD population. This case highlights the challenges of managing hyperinsulinemia and hypoglycemia in ESRD, underscoring the need for further research to define baseline insulin, proinsulin, and C-peptide levels in this population to improve diagnosis and management. Presentation: Sunday, July 13, 2025