SUN-857 - Rare Case of Type B Insulin Resistance Syndrome associated with Systemic Lupus Erythematosus

Introduction:
Type B insulin resistance (Type B IR) is a rare autoimmune disorder characterized by severe insulin-resistant hyperglycemia mediated by anti–insulin receptor antibodies and frequently associated with systemic lupus erythematosus (SLE).

Case Description:
A 47-year-old woman with hypothyroidism and type 1 diabetes diagnosed at age 23 presented with uncontrolled hyperglycemia. She had been well controlled on a basal–bolus regimen until she developed COVID-19, followed by arthralgia and worsening hyperglycemia despite escalating insulin doses. Later, the patient was admitted with DKA requiring high (30-100 U/h) insulin infusion. Prednisone was initiated during hospitalization, with improvement in glycemia; however, hyperglycemia recurred with taper and discontinuation of steroids. Given refractory hyperglycemia and positive anti-insulin antibodies, along with steroid-responsive glycemic improvement suggesting an underlying autoimmune process, type B insulin resistance was suspected. Concurrently, she was found to have active SLE that remained refractory despite aggressive therapy. She was managed with high-dose insulin and prednisone, with subsequent addition of GLP-1/GIP receptor agonists during follow-up, resulting in improvement of HbA1c from 15% to 7.9%. Anti–insulin receptor antibody testing was sent to Europe to confirm Type B IR.

Discussion:
This case illustrates a rare presentation of Type B IR in a patient with type 1 diabetes who responded to steroids. Although glucocorticoids typically worsen hyperglycemia, improvement in this case supports an antibody-mediated mechanism.
The temporal association between COVID-19 infection and worsening of pre-existing SLE along with onset of Type B insulin resistance suggests a possible post-infectious autoimmune trigger, as SARS-CoV-2 has been associated with immune dysregulation and de novo autoantibody formation.
Glycemic control further improved with the addition of a GLP-1/GIP receptor agonist, likely through insulin-sensitizing and anti-inflammatory effects. Although standard therapy includes rituximab, cyclophosphamide, and steroids, this patient showed significant improvement with the addition of GLP-1/GIP; yet, long-term outcomes remain uncertain.
In this context, diagnosis requires anti–insulin receptor antibody testing, which is not available in the U.S., often necessitating international referral and potentially delaying diagnosis.

Conclusion:
This case highlights the interaction between autoimmune insulin resistance, active SLE, and a possible post-COVID-19 immune trigger. Paradoxical response to steroids and improvement with GLP-1/GIP therapy suggest important therapeutic implications. Expanded access to anti–insulin receptor antibody testing may allow earlier diagnosis and management of this rare, potentially reversible condition.

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