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A case report and literature review of proton pump inhibitors inducing insulin autoimmune syndrome

Zhang W, Wen J, Qi S, Zhang G, Yang X, Zeng L, Xu W, Deng H

Frontiers in endocrinology, 2026

Abstract

Background: Insulin autoimmune syndrome (IAS) is an autoimmune endocrine disorder characterized by hyperinsulinemia, positive insulin autoantibodies (IAA), and hypoglycemia. IAS was previously thought to be induced by drugs containing thiol groups.

Objective: We describe a case highlighting that IAS may be temporally associated with a proton pump inhibitor (PPI) exposure. This article reports a patient who took beraprost sodium, clopidogrel, atorvastatin calcium, and the PPI pantoprazole and was subsequently diagnosed with IAS, presenting with a high IAA level, refractory hypoglycemia, and markedly elevated insulin levels. The patient's hypoglycemic episodes were ultimately relieved after discontinuation of the PPI, accompanied by a gradual decrease in the IAA level to the normal range.

Key findings: HLA analysis revealed HLA-DRB1*0403, DQB1*0302, and DQA1*0301, indicating the patient's genetic susceptibility to IAS, which was possibly triggered by the PPI.

Clinical relevance: This case report may alert clinicians to possible PPI-associated IAS, helping to avoid misdiagnosis and enable patients to receive timely treatment.

How strong is the evidence?

Evidence Hub reads this as a case report, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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