A case of extreme insulin resistance due to high levels of insulin receptor autoantibodies (type B insulin resistance)

Case presentation: A 45 yo woman presented with weight loss of 20 kg within 4 months and excessive glucose levels > 500 mg/dl, that could not be controlled with extreme insulin doses of 600 to 800 IU/d (administered via insulin pump). Strikingly, the patient suffered from unusually widespread acanthosis nigricans. Because of the severity of the insulin resistance combined with features of insulin deficiency, an autoimmune disorder with production of antibodies against the insulin receptor was suspected.

Investigation: Elevated anti-SS-A, anti-ds-DNA and anti-RNP levels demonstrated presence of an autoimmune disease. Ultimately, immunoprecipitation revealed high levels of insulin receptor autoantibodies (Fig. 1).

Treatment: Immunosuppressive therapy with immunoglobulin i.v. (20 g/d for 6 days) had no effect on glucose levels or insulin dose. Similarly, plasmapheresis (5x in 1 week) could not improve the severe insulin resistance. As the patient's condition was deteriorating with further weight loss, we started rituximab (750 mg/m² in two doses two weeks apart) together with cyclophosphamide (100 mg/d p.o.) and dexamethasone 40 mg/d for 4 days (Malek R et al. JCEM 2010).

Outcome: Two months after initiation of rituximab therapy, the patients well being has greatly improved. Fasting glucose levels ranged from 80 to 110 mg/dl and HbA1c decreased from 11.8 to 9.9% as was the required insulin dose 300 IU/d.

Discussion: We report a case of extreme insulin resistance with features of insulin deficiency due to high levels of insulin receptor autoantibodies which could be treated with rituximab, cylophosphamide and steroids. Further improvement is expected in the next months.

Fig. 1: Anti-INSR from patient 1070 and controls