MON-622 Severe Insulin Resistance in a Patient with Generalized Lipodystrophy

Abstract Disclosure: D. Kaul: None. M. Paravastu: None. M. Shah: None. R. Patel: None. T. Yasmeen: None. M.H. Kazi: None. Introduction: Lipodystrophy is classified into two main types: generalized and partial, based on the extent of fat loss and further as genetic or acquired, depending on its underlying cause. The prevalence ranges from 1 in 1 million for familial partial lipodystrophy to 1 in 10 million for congenital generalized lipodystrophy. Its manifestation often includes severe metabolic disturbances, including dyslipidemia, insulin resistance, and increased risks of renal, hepatic, and cardiovascular diseases.Clinical Case: A 72-year-old female with type 2 diabetes, chronic kidney disease stage 3, and hyperlipidemia presented with hyperglycemia, severe weight loss, polydipsia, and polyuria. Her diabetes regimen included insulin degludec U-200 (76 units daily), insulin aspart (35 units with meals), and Trulicity (3 mg weekly). She reported missing several doses of insulin and had lost 78 lbs over the past year. On exam, she had generalized subcutaneous fat loss, weighing 54.1 kg with a BMI of 18.68 kg/m². Labs showed a glucose level of 614 mg/dL (normal range: 70-99 mg/dL), without evidence of diabetic ketoacidosis, HbA1c of 8.2% (normal range: 4.5-5.6%), C-peptide of 8.9 ng/mL (normal range: 0.8-3.9 ng/mL), and a triglyceride level of 36 mg/dL (normal range: <=149 mg/dL). Due to severe hyperglycemia, a continuous insulin infusion was started, requiring 931 units over 24 hours plus 100 units of insulin glargine. Given her phenotype and insulin resistance, lipodystrophy was suspected. Leptin was <0.4 ng/mL (normal range: 0.5-15.2 ng/mL), and Cushing syndrome was ruled out with a screening test, confirming generalized lipodystrophy. She was started on metreleptin and discharged with insulin degludec U-200 (90 units twice daily), insulin aspart (60 units three times daily), tirzepatide (2.5 mg weekly), and empagliflozin (25 mg daily).Discussion: Insulin resistance in lipodystrophy arises from the lack of functional adipose tissue, impairing the body’s ability to store excess energy as fat. This leads to ectopic fat deposition in the liver and muscle, disrupting insulin signaling. Leptin replacement therapy is a key treatment, as low leptin levels—due to reduced adipose tissue—contribute significantly to the metabolic abnormalities seen in lipodystrophy. Metreleptin, along with dietary modifications, is the first-line treatment, improving insulin sensitivity, reducing nonalcoholic steatohepatitis, alleviating cardiac hypertrophy, and lowering mortality. Though rare, lipodystrophy requires early recognition for appropriate screening and treatment. Presentation: Monday, July 14, 2025