Drawing on the first theory, the clinicians decided to test out a new insulin in the patient, one she had never been exposed to, and also one structurally different from the previous insulins. They hoped that this new insulin could “fly under the radar” and allude the patient’s immune system. Glulisine, NPH, and detemir were chosen as candidates, however a decision was made to test out detemir.

After just one 40 unit dose of detemir, the patient’s glucose levels fell to 292mg/dL within 24 hours. The detemir dose was titrated for optimal effect and subsequently the insulin drip was discontinued. While in the intensive care unit, the patient’s average blood glucose was around 181mg/dL. She was eventually discharged on a dose of 55 units twice daily. 

Dramatic insulin resistance, as seen with this patient, is a rare occurrence and complete loss of synthetic insulin efficacy through antibody neutralization has not been previously reported. Why the patient responded to detemir is not quite clear, however it does differ structurally from glargine, aspart, and regular insulin and this difference may have protected it from neutralization; some studies have shown that detemir may be less immunogenic than other insulins. These small changes in structure can have a large clinical impact (ie, L-dopa for Parkinson’s disease, sotalol for arrhythmia) and may make the difference between whether a treatment works or doesn’t.


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The authors conclude by stating that “poor outcomes with one medication should not be used to rule out the efficacy of all related medications.

Reference

1. Kandel, S.M., Cosgriff, J.A. Flying under the radar: treatment of refractory hyperglycemia. Endocrinology, Diabetes & Metabolism. 2016; doi: 10.153/EDM-16-0052.