Mycophenolate Mofetil and Plasmapheresis: A Treatment Option for Severe Insulin Resistance caused by Insulin Antibodies

Objective: Insulin antibody (IA)-mediated insulin resistance (IR) is a rare condition for which immunosuppressive regimens have been described. However, these raise the risk of infection, and the drugs may not be effectively metabolized in patients with liver disease. A 61-year old male with type 2 diabetes mellitus and antibody-mediated IR who required >800 units of daily insulin presented with acute decompensation of his preexisting cirrhosis from recurrent diabetic ketoacidosis. Laboratory tests confirmed an IA level of >625 μU/mL (reference: <5.0 μU/mL). Methods: Centrifugal plasmapheresis and mycophenolate mofetil (MMF) were used to treat the patient to achieve glycemic control. Continuous glucose monitoring was implemented to monitor glycemic control pre- and posttherapy. Laboratory evaluation included levels of IA, C-peptide, insulin-like growth factor-1, growth hormone, salivary cortisol, zinc transporter 8, glutamic acid decarboxylase 65-kilodalton isoform antibody, and islet-cell antibodies. Results: We initiated MMF followed by 5 sessions of plasmapheresis, leading to an overall 77.3% reduction from pretherapy insulin requirements after 6 months without further episodes of diabetic ketoacidosis or infection. The cirrhosis stabilized, and there was an improvement in HbA1C from 8.7% (72 mmol/mol) to 6.6% (49 mmol/mol) and time in euglycemic range from 30% to 61%. Conclusion: This is the first report of MMF and centrifugal plasmapheresis use to mitigate the effects of IA-mediated IR in a patient with cirrhosis. We recommend further studies to determine the utility of this treatment to improve care for patients at high risk for IA-mediated IR.