SUN-516 - Treatment of Subcutaneous Insulin Resistance Syndrome with Co-Administered Subcutaneous Heparin and Insulin

Background: Subcutaneous Insulin Resistance Syndrome is a rare condition characterized by disproportionately high subcutaneous insulin requirements, contrasted with much lower intravenous insulin infusion rates. This condition presents management challenges in both inpatient and outpatient settings. We demonstrate therapeutic strategies with the use of ultra-rapid acting insulin, co-administered with heparin, to improve glycemic control.

Clinical

Case: A 33 year-old female patient presented to our hospital for evaluation of marginal zone lymphoma and hemophagocytic lymphohistiocytosis, with severe pancytopenia and hemolytic anemia secondary to warm antibodies. She required Dexamethasone 4mg daily for treatment. Glycemic control during admission was difficult, requiring frequent insulin infusions with widely variable rates (1-20 units/hour) and persistent hyperglycemia on subcutaneous insulin. On subcutaneous insulin regimens, blood glucose values were up to 500-600 mg/dL despite a total daily insulin dose of approximately 200 units of U100 insulin. Our patient was diagnosed with diabetes mellitus in 2018, with multiple sources documenting type 2 disease. C-peptide checked during admission was < 0.02 ng/mL with serum glucose of 124 mg/dL, confirming diabetes mellitus type 1. GAD65 antibody level was elevated to 96 IU/mL (Normal < 5 IU/mL). Escalating subcutaneous insulin requirements and transition to Humulin R U-500 did not achieve glycemic control. Insulin requirements peaked with 380 units of Humulin R U500 with blood glucose still spiking to 300-500 mg/dL and anion gap intermittently increasing, with labs indicating diabetic ketoacidosis. Intravenous insulin infusion quickly restored glycemic control with significantly lower doses. This presentation was consistent with Subcutaneous Insulin Resistance Syndrome, and treatment with combined heparin and insulin was initiated to enhance subcutaneous absorption. Prior case reports have shown co-administration of heparin and insulin in a 1:1 ratio by volume. We started by administering lispro insulin 20 units (0.2mL) next to heparin 0.1mL or 1000 units based on our concentration of heparin available at our pharmacy. After this technique, response to subcutaneous insulin significantly improved, with better glucose control and lower total daily insulin requirements close to 80 units of U100 lispro and NPH 60 units daily. On discharge, we recommended therapy with insulin lispro–aabc 32 units with meals which has been shown to aid insulin absorption through Treprostinil and citrate. Approximately 1 month after discharge, an outpatient metabolic panel showed improved blood glucose, with a value of 130 mg/dL.

Conclusion: Given the paucity of reported cases, our report emphasizes the need for awareness, timely diagnosis, and prompt initiation of appropriate therapy for Subcutaneous Insulin Resistance Syndrome.

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