SUN-186 Insulin Antibody Associated Severe Insulin Resistance Leading to Uncontrolled Hyperglycemia

Abstract

Background: Severe insulin resistance is unusual in young patients with type 1 DM and normal BMI. We report a case of severe insulin resistance attributed to the development of insulin antibodies. Clinical Case: An 18 year old male with uncontrolled Type 1 DM was admitted to psychiatry for management of a delusional disorder. His home insulin regimen consisted of degludec 56 units daily and aspart 30 units before meals. He weighed 75 kg with a BMI of 27.5 kg/m2. Initial blood work revealed hyperglycemia with glucose of 549 mg/dl, HbA1C of 10%, C-peptide of <0.1 ng/ml (0.9-7.1 ng/ml), and no evidence of urinary ketones, acidemia, hyperosmolarity or thyroid dysfunction. He was started on a basal bolus regimen with a total daily dose of 0.9 units/kg. His hyperglycemia persisted despite rising standing insulin doses and metformin 1000 mg twice daily was added with minimal improvement in glycemic control. Due to persistent hyperglycemia despite rising insulin doses, insulin antibody titers were measured and found to be elevated at 4.4 U/ml (<0.4 U/ml.) When his psychiatric symptoms stabilized, he was discharged on a basal bolus regimen with total daily dose of 2.6 units/kg and metformin 1000 mg twice a day with improved glycemic control. Conclusion: Development of insulin antibodies is known to occur in type 1 diabetics using animal preparations of insulin but far less commonly in patients receiving recombinant human insulin or insulin analogues. Factors related to their development include the type of insulin (animal insulin having higher immunogenicity), mode of delivery (increased levels seen with insulin pump use and more frequent injections) and predisposing genetic factors such as certain HLA types. In some individuals, these antibodies may be clinically insignificant while others may develop severe insulin resistance with highly variable glycemic control. Often these patients experience marked hypoglycemia at night yet are hyperglycemic during the day. Treatment options include switching insulin formulations, insulin sensitization with metformin or thiazolidinediones, stimulation of insulin production with sulfonylureas or GLP-1 receptor agonists and immunosuppression with glucocorticoids, mycophenolate or cyclophosphamide. In patients who fail these treatments, plasmapheresis has been described as an alternative. In conclusion, the presence of insulin antibodies should be considered in patients with severe hyperglycemia despite increasing doses of insulin.