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Unexplained hypoglycemia in individuals receiving insulin therapy may reflect an immune-mediated process rather than excessive insulin exposure. A retrospective analysis published in Diabetes, Metabolic Syndrome and Obesity assessed clinical characteristics and predictors of exogenous insulin antibody syndrome (EIAS) in patients with diabetes undergoing insulin autoantibody testing.

The study included 120 patients with diabetes admitted between June 2023 and March 2024 with available insulin autoantibody (IAA) results. Participants were categorized into control and EIAS groups, and 37 individuals met criteria for EIAS. Clinical characteristics were compared between groups. Multivariate logistic regression identified independent risk factors. Receiver operating characteristic (ROC) analysis evaluated the diagnostic performance of fasting insulin.

Compared with controls, individuals with EIAS were older and had longer diabetes duration. They were more frequently treated with insulin aspart or premixed human insulin and received higher daily insulin doses. EIAS patients had lower fasting blood glucose and glycated hemoglobin (HbA1c) but higher fasting and 2-hour postprandial insulin levels and higher Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Multivariate analysis showed that fasting insulin was independently associated with EIAS risk (OR 1.03 per 1 uU/mL increase; 95% CI 1.00-1.05). ROC analysis demonstrated an AUC of 0.782 (95% CI 0.691-0.872) with an optimal cutoff of 6.975 uU/mL, corresponding to 73.0% sensitivity and 81.9% specificity.

Individuals with EIAS showed features including older age, longer diabetes duration, higher insulin doses, hypoglycemia, and hyperinsulinemia. Fasting insulin levels demonstrated diagnostic performance for identifying EIAS and may support clinical evaluation of suspected cases.

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Key highlights

  • Among 120 patients with diabetes, 37 met criteria for EIAS based on insulin autoantibody testing.
  • Fasting insulin was independently associated with EIAS (OR 1.03 per 1 uU/mL increase; 95% CI 1.00-1.05).
  • Diagnostic performance of fasting insulin: AUC 0.782 (95% CI 0.691-0.872); cutoff 6.975 uU/mL with 73.0% sensitivity and 81.9% specificity.
  • EIAS cases were characterized by older age, longer diabetes duration, higher insulin doses, hypoglycemia, and hyperinsulinemia.
Source

Zhou J, Li J, Wang Z, et al. Clinical characteristics and risk factors of exogenous insulin antibody syndrome in patients with diabetes: a retrospective cross-sectional study. Diabetes Metab Syndr Obes. Published March 7, 2026. doi:10.2147/DMSO.S571981

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A retrospective study of 120 patients with diabetes found higher fasting insulin independently associated with exogenous insulin antibody syndrome.

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