Successful immunosuppressive therapy in insulin resistant diabetes caused by anti-insulin receptor autoantibodies

A 45-year-old, non-obese female patient with no previous history of insulin administration was found to have extreme insulin resistance and abnormally high plasma immunoreactive insulin in the absence of anti-insulin antibodies in the serum. Clinically, there was no ketonuria. The patient also had evidence of Sjogren's syndrome with several immunologic features including hypergammaglobulinemia, positive antinuclear antibodies, accelerated erythrocyte sedimentation rate and leukopenia. Plasma pancreatic glucagon and C-peptide were elevated, but other endocrinologic abnormalties were not present. In this patient the insulin resistance appeared to be due to anti-insulin receptor antibodies which could be detected even in 1:500 dilution of serum. Immunosuppressive therapy with prednisolone and cyclophosphamide resulted in a decreased level of serum gamma globulin and a concomitant decrease of blood glucose level. After immunosuppressive therapy for eight months, the diabetic syndrome disappeared completely and anti-receptor antibodies in the serum were no longer detectable. Furthermore, insulin sensitivity returned to normal. However, the patient's glucose tolerance deteriorated after the temporary termination of cyclophosphamide treatment and the lowering of prednisolone dosage.