A Pair of Contrasting Cases of Type B Insulin Resistance with Response to Immunosuppressive Protocol
Presentation Number: MON 611
Date of Presentation: April 3rd, 2017
Madhavi Averneni*1, Mohammad Raihan Azad2, Jennifer Giordano3, Maitri Shelly Kalia-Reynolds4, Fiona J Cook5 and Caroline Houston4
1ECU ENDOCRINOLOGY, GREENVILLE, NC, 2ECU division of endocrinology, Greenville, NC, 3East Carolina University/Brody School of Medicine, Greenville, NC, 4East Carolina University, Greenville, NC, 5Brody School of Medicine, Greenville, NC
Type B insulin resistance (TBIR) is a rare syndrome in which high titer polyclonal autoantibodies exhibit antagonistic activity against the insulin receptor, leading to extreme insulin resistance. This syndrome occurs most often in african american women with concomitant rheumatologic disease . The National Institutes of Health (NIH) have conducted the only prospective clinical trial to date using a combination of rituximab, cyclophosphamide, and corticosteroids to induce disease remission. We previously reported the third case of TBIR successfully treated with this protocol outside of the NIH. We now report a second case of TBIR treated at our institution and draw comparisons with our index case.
Our index patient was a 68 year old African American woman with mixed connective tissue disease who presented with rapid weight loss, worsening diabetes mellitus (Hgb A1c 11.1%), alopecia, hirsutism, and acanthosis nigricans. Hyperglycemia persisted despite use of metformin and 1,500 units of insulin daily. The combination of hyperinsulinemia, high adiponectin (30.3 ug/mL), and high molar ratio of insulin to C-peptide (9:1) reflected impaired insulin receptor function and impaired clearance of insulin. Triglyceride (TG) level was 66 mg/dL. Serum analysis confirmed the presence of anti-insulin receptor antibodies. After two cycles of the NIH immunosuppressive protocol, her CD-19 cell count fell to 1% and her insulin requirement dissipated. She achieved full remission 12 months after the diagnosis.
Our second patient was a 42 year old Jamaican woman with systemic lupus erythematosus who presented with rapid weight loss, worsening diabetes mellitus (Hgb A1c 14.7%), alopecia, and profuse acanthosis nigricans of the face and extremities. She required over 6,500 units of insulin per day and metformin to maintain serum glucose <300 mg/dL. She was noted to have severe hyperinsulinemia, normal adiponectin (13 ug/mL), TG 87 mg/dL, and a high molar ratio of insulin to C-peptide (50:1). Serum analysis was intensely positive for anti-insulin receptor antibodies. After two cycles of treatment with the NIH protocol, her CD-19 cell count decreased to 1% and her insulin was gradually tapered off over a 2 month period. Due to recurrent leukopenia, she was switched from cyclophosphamide to azathioprine shortly after the end of the second treatment cycle. She was discharged on metformin with normal glucose levels.
The biochemical triad of high insulin levels, normal-high adiponectin, and low triglycerides in an individual with acanthosis nigricans, rapid weight loss and autoimmune disease has been proposed as a working clinical definition for TBIR. Our similar, yet contrasting, cases support the notion that higher antibody titers correlate with increasing disease severity. Even in the more severe case, the NIH immunosuppressive protocol proved successful.
Nothing to Disclose: MA, MRA, JG, MSK, FJC, CH