Diagnostic efficacy of fasting insulin-to-C-peptide ratio in exogenous insulin autoimmune syndrome

Background The early-stage diagnosis of exogenous insulin autoimmune syndrome (EIAS) remains a significant clinical challenge for endocrinologists. This study aimed to investigate the diagnostic predictive utility of the fasting insulin-to-C-peptide ratio in EIAS. Methods Diabetic patients with insulin autoantibody (IAA) testing admitted to our hospital between June 2023 and March 2024 were retrospectively enrolled. Participants were stratified into control and EIAS groups based on IAA status. A comparative analysis of EIAS clinical features was performed, with receiver operating characteristic (ROC) curve analysis used to determine the predictive efficacy of the fasting insulin/C-peptide ratio for EIAS. Results Among 120 enrolled diabetic patients with IAA testing, 37 (30.8%) fulfilled the EIAS diagnostic criteria. Compared with patients in the control group, patients in the EIAS group were significantly older and had a longer duration of diabetes, demonstrated greater use of aspart insulin and recombinant human insulin formulations, and required higher insulin dosages. The EIAS cohort exhibited lower fasting glucose and HbA1c levels, alongside markedly elevated fasting and 2-h postprandial insulin concentrations and increased HOMA-IR values. ROC analysis established the fasting insulin/C-peptide ratio as a moderately accurate predictor of EIAS (AUC 0.802; 95% CI 0.724–0.880), with an optimal diagnostic threshold of 5.215 μU/ng providing 78.4% sensitivity and 77.1% specificity. Conclusion Advanced age, prolonged diabetes duration, elevated insulin dosage requirements, recurrent hypoglycemia, and hyperinsulinemia constitute characteristic clinical features of EIAS. The fasting insulin/C-peptide ratio demonstrated favorable diagnostic performance, positioning it as a practical screening biomarker for EIAS.

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Journal
Frontiers in Medicine
Published
2026-01-29
DOI
https://doi.org/10.3389/fmed.2026.1710461
Primary Topic
Diabetes and associated disorders
Type
article
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article

Diagnostic efficacy of fasting insulin-to-C-peptide ratio in exogenous insulin autoimmune syndrome

Ziyue Wang, Chunyan Zhang, Chen Guo, Na Feng et al.
Frontiers in Medicine
Diabetes and associated disorders
article

Diagnostic efficacy of fasting insulin-to-C-peptide ratio in exogenous insulin autoimmune syndrome

Ziyue Wang, Chunyan Zhang, Chen Guo, Na Feng, Juanjuan Wu, Nenghan Zhang, Jing Zhou, Yongqin Li, Tuo Han, Jiajun Li, Yan Zhang
article en

Abstract

Background The early-stage diagnosis of exogenous insulin autoimmune syndrome (EIAS) remains a significant clinical challenge for endocrinologists. This study aimed to investigate the diagnostic predictive utility of the fasting insulin-to-C-peptide ratio in EIAS. Methods Diabetic patients with insulin autoantibody (IAA) testing admitted to our hospital between June 2023 and March 2024 were retrospectively enrolled. Participants were stratified into control and EIAS groups based on IAA status. A comparative analysis of EIAS clinical features was performed, with receiver operating characteristic (ROC) curve analysis used to determine the predictive efficacy of the fasting insulin/C-peptide ratio for EIAS. Results Among 120 enrolled diabetic patients with IAA testing, 37 (30.8%) fulfilled the EIAS diagnostic criteria. Compared with patients in the control group, patients in the EIAS group were significantly older and had a longer duration of diabetes, demonstrated greater use of aspart insulin and recombinant human insulin formulations, and required higher insulin dosages. The EIAS cohort exhibited lower fasting glucose and HbA1c levels, alongside markedly elevated fasting and 2-h postprandial insulin concentrations and increased HOMA-IR values. ROC analysis established the fasting insulin/C-peptide ratio as a moderately accurate predictor of EIAS (AUC 0.802; 95% CI 0.724–0.880), with an optimal diagnostic threshold of 5.215 μU/ng providing 78.4% sensitivity and 77.1% specificity. Conclusion Advanced age, prolonged diabetes duration, elevated insulin dosage requirements, recurrent hypoglycemia, and hyperinsulinemia constitute characteristic clinical features of EIAS. The fasting insulin/C-peptide ratio demonstrated favorable diagnostic performance, positioning it as a practical screening biomarker for EIAS.

Frontiers in MedicineVol. 13
Second Affiliated Hospital of Xi'an Jiaotong University (CN), Xi'an Jiaotong University (CN)
National Natural Science Foundation of China, Natural Science Foundation of Shaanxi Province
Good health and well-being
Openalex Percentile: Top 70%
Diabetes and associated disorders
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