Instructor University of Illinois at Chicago Chicago, Illinois, United States
Introduction : Hyperglycemia is a common phenomenon in hospitalized patients, exacerbated by infection, stress, or medications, and treated with subcutaneous or IV insulin. In rare cases, however, even very high doses of insulin are unable to control hyperglycemia. In these situations, clinicians will seek an alternative etiology of the resistance. We present a case of severe antibody-mediated insulin resistance requiring >1000 units of intravenous insulin daily successfully treated with U-500 insulin.
Case(s) Description : A 40-year-old female with Type 2 DM and panhypopituitarism secondary to craniopharyngioma resection presented with altered mental status. She was treated for obesity hypoventilation syndrome, adrenal insufficiency, and AVP deficiency and improved clinically; however, as she was preparing for discharge, her insulin requirements steeply increased. Despite increasing doses of subcutaneous insulin, she remained persistently hyperglycemic, and so was started on an insulin drip. This did not resolve her hyperglycemia, despite receiving >1500 units a day. Liraglutide was added, but her insulin requirements continued to rise. She was given 200 units ofU-500 insulin with rapid improvement in glycemic control and weaned off the insulin drip. Empagliflozin and pioglitazone were started shortly after. Insulin antibodies eventually returned positive. She was transitioned to glargine and aspart, but quickly became hyperglycemic and was therefore transitioned back to U-500 and eventually discharged on U-500 along with liraglutide, empagliflozin, and pioglitazone.
Discussion : It’s estimated that about half of all patients taking exogenous insulin develop insulin antibodies. These antibodies are not always neutralizing; however, multiple case reports have described insulin resistance resulting from antibodies. In some of these cases, glycemic control is achieved simply with transition to non-insulin agents or different insulin formulations. In other cases, patients require high-dose glucocorticoids, plasmapheresis, and/or immunosuppressants. Our patient had a very rapid improvement immediately after receiving U-500, which is very curious and somewhat confounding, as U-500 insulin is structurally identical to regular insulin. A previous case report also described the use of U-500 treatment for antibody-mediated insulin resistance in 3 separate patients, despite no difference in antibody affinity between the two insulin preparations in competition experiments. The fact that she was unable to be transitioned back to basal/bolus further indicates that U-500 was therapeutic, and not just coincidentally administered with the spontaneous resolution of insulin resistance. This case shows that when faced with settings of otherwise unexplainable insulin resistance, clinicians should keep insulin antibody production high on their differentials and consider U-500 in the quest for glycemic control.
