Variables associated with endogenous hyperinsulinism in hypoglycemia diagnosis. Could the 72-hour fasting test be shortened in low-risk patients?

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Background: The 72-hour fasting test remains the standard for the diagnosis of endogenous hyperinsulinism. We investigated which variables could identify patients at low risk for endogenous hyperinsulinism, in whom a shortening of the 72-hour fasting test could be considered. Methods: This multicenter, retrospective study included 64 individuals (46 women, median age 45 years) without diabetes who underwent 72-hour fasting tests for the etiologic diagnosis of hypoglycemia. Pre- and intra-test variables were collected, including point-of-care glucose trajectories during the test. Testing was stopped before 72 h if symptomatic serum glucose <55 mg/dL or asymptomatic serum glucose ≤45 mg/dL occurred. Endogenous hyperinsulinism was diagnosed in individuals who had serum glucose <55 mg/dL, serum insulin ≥3.0 μU/mL, and serum C-peptide ≥0.6 ng/mL. Results: Patients with endogenous hyperinsulinism (n = 10) had steeper descending point-of-care glucose trajectories (p < 0.001) than those without it. Older age and lower minimum pre-test serum glucose concentrations were independently associated with endogenous hyperinsulinism. A calculator for probability prediction of endogenous hyperinsulinism was developed including these variables and sex (AUC = 0.94). Older age, female sex, lower body mass index, and lower minimum point-of-care glucose during the first 24 h of fasting were independently associated with serum glucose <55 mg/dL after the first 24 h of fasting. A calculator for predicting probability of serum glucose <55 mg/dL after the first 24 h of fasting was developed including these variables (AUC = 0.84). Conclusions: Pre- and intra-test variables can identify individuals at low risk for endogenous hyperinsulinism, in whom shortening the 72-hour fasting test could be considered.

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González-Vidal, T., Lado-Baleato, Ó., Masid, I., Gándara-Gutiérrez, C., Martínez-Tamés, G., Ares, J., Lambert, C., Riestra-Fernández, M., Gude, F., Delgado, E., & Menéndez-Torre, E. (2025). Variables associated with endogenous hyperinsulinism in hypoglycemia diagnosis. Could the 72-hour fasting test be shortened in low-risk patients? Journal of Clinical and Translational Endocrinology, 40. https://doi.org/10.1016/J.JCTE.2025.100386

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ÓLB was supported by ISCIII Support Platforms for Clinical Research (ISCIII/PT23/00118/Co-funded by European Union). This research did not receive any other specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license
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