Clinical Characteristics and Risk Factors of Exogenous Insulin Antibody Syndrome in Patients with Diabetes: A...

Insulin autoimmune syndrome (IAS) is a rare hypoglycemic disorder often confused with insulinoma or insulin overdose. Patients with diabetes on insulin therapy increasingly show insulin autoantibodies (IAAs), presenting symptoms similar to classic IAS, termed exogenous insulin antibody syndrome (EIAS). This study examines EIAS clinical features and risk factors.

Patients with diabetes with IAA test results, admitted to our hospital between June 2023 and March 2024 were retrospectively enrolled. Participants were stratified into control and EIAS groups on the basis of IAA status. Clinical characteristics were compared between groups, independent risk factors for EIAS were identified by multivariate logistic regression, and the diagnostic utility of fasting insulin for predicting EIAS was assessed with receiver-operating-characteristic (ROC) curve analysis.

Of 120 patients with diabetes and available IAAs results, 37 met criteria for EIAS. Compared with controls, EIAS patients were older, had longer diabetes duration, were more often treated with insulin aspart or premixed human insulin, and received higher daily insulin doses. Paradoxically, EIAS patients had markedly lower levels of fasting blood glucose and HbA1c, while higher fasting and 2-h post-prandial insulin concentrations, as well as HOMA-IR. Multivariate logistic regression analysis showed that elevated fasting insulin levels were independently associated with increased risk of EIAS. For every 1 uU/mL increase in fasting insulin, the risk of EIAS increased by 3% (OR = 1.03, 95% CI: 1.00-1.05). The fasting insulin level demonstrated high overall diagnostic and predictive efficacy for EIAS, with an area under the curve (AUC) of 0.782 (95% CI: 0.691-0.872). The optimal diagnostic cutoff value was 6.975 uU/mL, with a sensitivity of 73.0% and a specificity of 81.9%.

EIAS patients were identified with advanced age, prolonged diabetes duration, high insulin dosage, hypoglycemia, and hyperinsulinemia. Fasting insulin level is independently associated with EIAS risk and demonstrates good diagnostic performance.