Abstract Disclosure: A.A. Zakkar: None. M. Fadanelli: None. M. Al Mushref: None. Patient is a 46-year-old African American female with a medical history of Diabetes Mellitus Type 1 for 20 years, hypothyroidism, rheumatoid arthritis and celiac disease who presented with a complaint of dizziness and heavy menstrual periods. When she presented, labs were significant for a glucose of 513 mg/dL, anion gap of 22 with a bicarbonate of 8, HbA1c of 10%, Hemoglobin of 8.1 and UA revealed ketones and she was thus started on an insulin drip for diabetic ketoacidosis. Patient was also complaining of a cough and weakness and thus a sputum sample was obtained which was positive for Streptococcus pneumoniae and she was started on antibiotics. At the time of arrival the patient was A&Ox4 and stated that her glucose has been really difficult to control over the last 6 months after she had been infected with COVID-19 and over that time she has also lost approximately 50 lbs. She stated that one month prior to the patient having COVID-19 infection, she was taking aspart 20 units per/meal and detemir 32 units qAM and 62 units qHS, and had an HbA1c of 8.5%. Just prior to presentation, the patient was taking 70 units of the U-100 aspart insulin per meal and 60 units of glargine U300 twice daily with persistent hyperglycemia. Insulin antibodies were tested and returned remarkably high. GAD-65 antibody was also high. The patient's glucose remained in the 500-600 mg/dL range and the acidosis worsened to a pH of 6.9 despite receiving continuous intravenous insulin aspart at 30units/hr with the addition of detemir 100 units q12-hours. The patient's acidosis resolved after two days and she was transitioned to Humulin R-U-500 at 80 units TID and aspart 40 units every 4-hours for tube feeding coverage but was still hyperglycemic in the 200-300 mg/dl range. Due to autoimmunity and extreme insulin requirements the patient was started on methylprednisolone 20 mg q8hr with improvement of glucose to the 150 to 200 mg/dl range and a decrease in her daily insulin requirements and thus she was transitioned to 60mg of prednisone daily with a 10mg taper weekly. By the time she was discharged 2 weeks later, her glucose was more controlled and her insulin requirements were decreased to aspart 14 units per/meal and detemir 40 units BID. Conclusion: In patients with diabetes mellitus who develop extreme insulin resistance following COVID -19 infection, consider autoimmune etiology in the differential diagnosis, such as insulin inactivating antibodies or insulin receptor blocking antibodies. In our experience laboratory testing of the specific antibodies was not available. Management of autoimmune mediated hyperglycemia will require immunosuppressivetherapy. Presentation: Thursday, June 15, 2023