Insulin autoimmune hypoglycemia unmasking monoclonal gammopathy in type 2 diabetes

Insulin autoimmune syndrome (IAS), also known as Hirata disease, is a rare cause of spontaneous hypoglycemia due to circulating insulin autoantibodies, most commonly described in East Asian individuals and those exposed to sulfhydryl-containing drugs. We describe a 58-year-old South Asian man with type 2 diabetes mellitus who presented with recurrent fasting and postprandial hypoglycemia despite cessation of all glucose-lowering medications. A spontaneous episode confirmed Whipple triad: plasma glucose 38 mg/dL (SI: 2.1 mmol/L; reference range, 70-99 mg/dL [SI: 3.9-5.5 mmol/L]), markedly elevated serum insulin at 156 µIU/mL (SI: 1083 pmol/L; reference range, 2.6-24.9 µIU/mL [SI: 18-173 pmol/L]), and C-peptide of 5.8 ng/mL (SI: 1.9 nmol/L; reference range, 0.5-2.0 ng/mL [SI: 0.17-0.66 nmol/L]), with a negative sulfonylurea screen and markedly elevated insulin autoantibody titers. Polyethylene glycol precipitation confirmed antibody-bound insulin sequestration. Workup identified IgG-kappa monoclonal gammopathy of undetermined significance as the probable precipitant. Dietary modification, oral glucocorticoids, and acarbose achieved near-complete resolution of hypoglycemia with declining autoantibody titers over 4 weeks. This case highlights the importance of considering IAS in unexplained hyperinsulinemic hypoglycemia and the need to screen for plasma cell dyscrasias in atypical presentations.