SUN-513 - Novel Use of Humulin R U-500 in an Automated Insulin Delivery System Results in Stable Glycemic Control, Decreased Insulin Requirements, and Reduced Diabetes Burden in A Patient with Type 1 Diabetes and Severe Insulin Resistance

Background: The use of concentrated insulin with continuous subcutaneous insulin infusion (CSII) and automated insulin delivery (AID) remains off-label, with few reports involving AID and no published cases from Canada.

Case: We describe a 26-year-old woman with longstanding type 1 diabetes and severe insulin resistance, requiring over 200 units of insulin/day on multiple daily injections and approximately 120 units/day of insulin lispro 200 units/mL (U-200) after transition to AID with a Tandem t:slim X2 pump. She was switched to Humulin R U-500 (U-500R) to meet her high insulin requirements. At the time of transition to U-500R, the patient discontinued her longstanding GLP-1 agonist therapy due to gastrointestinal side effects, but this was restarted 10 months later.

Results: Three months following transition to U-500R, her glucose management indicator (GMI) was 7.5%, compared with 7.4% on U-200, her time in range (TIR) decreased from 60% to 55%, and time below range (TBR) increased from 1 to 2%. At 12 months, following re-initiation of GLP-1 agonist therapy, her GMI remained at 7.5% with 59% TIR and 1.5% TBR. Her average daily insulin requirements decreased to 34.3 units of U-500R (171.5 units U100 equivalent) from 121.9 units of U-200 (243.8 units U100 equivalent), while infusion set changes decreased from every 1.8 to 4.0 days. The patient reported improved satisfaction with lower pump volume demands and extended infusion set wear.

Conclusion: The use of U-500R in an AID system provided meaningful benefits for a patient with severe insulin resistance, resulting in decreased total daily insulin dose and less frequent infusion set changes while maintaining glycemic stability. Despite theoretical risks of stacking, delayed action, and nocturnal hypoglycemia, no significant increase in TBR was observed. Further studies are needed to define optimal pump parameters, absorption kinetics, and long-term safety.

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