Pathological mechanisms and therapeutic advances of tumor-associated hypoglycemia: from clinical challenges to precision intervention

Hu Guangqiang; Han Yun; Chen Li; Yan Ke

doi:10.16689/j.cnki.cn11-9349/r.2026.01.021

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Electronic Journal of Metabolism and Nutrition of Cancer ›› 2026, Vol. 13 ›› Issue (1) : 155-163. DOI: 10.16689/j.cnki.cn11-9349/r.2026.01.021

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Pathological mechanisms and therapeutic advances of tumor-associated hypoglycemia: from clinical challenges to precision intervention

Hu Guangqiang, Han Yun, Chen Li, Yan Ke

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Abstract

Tumor-induced hypoglycemia (TIH) is a severe paraneoplastic syndrome caused by tumors, either directly or indirectly, and associated with glucose metabolism disorders. Patients often exhibit autonomic nervous system excitation symptoms such as sweating, palpitations, and hunger. It frequently presents with consciousness disturbances or epilepsy as the primary or predominant symptoms. TIH is classified into two types: insulin cell tumor hypersecretion (ICTH), which results from excessive insulin secretion by islet cell tumors, and non-islet cell tumor hypersecretion (NICTH), which arises from mesenchymal or epithelial tumors secreting "large IGF-Ⅱ" insulin-like factors with abnormal regulation. This article provides a detailed summary and review of the pathological mechanisms, clinical challenges, and diagnostic and therapeutic advancements in TIH. The discussion delves into the pathological mechanisms of TIH, focusing on abnormal insulin/insulin-like growth factor secretion, tumor metabolic hijacking, and neuroendocrine regulatory imbalance, as well as the "tumor-host-neuroendocrine network" interaction. It also offers a cutting-edge summary of molecular diagnostic techniques, interventional strategies, and breakthroughs in targeted therapies, shifting the diagnostic and therapeutic approach from passive glycemic elevation to active regulation. The synergy between rhGH and vascular embolization, the application of IGF1R-targeted drugs, and the introduction of molecular subtyping concepts mark the dawn of the precision intervention era. Finally, the article analyzes current challenges in the field, such as delayed diagnosis and the lack of personalized treatment, and outlines the latest hot topics. Future research needs to overcome three major bottlenecks: widespread IGF profiling for early diagnosis, the development of highly selective "large IGF-Ⅱ" antagonists, and the establishment of interdisciplinary management pathways. This study aims to provide clinicians with a systematic management framework for TIH, offering a reference to facilitate the transition from passive treatment to proactive prevention in this field.

Key words

Tumor-associated hypoglycemia / Big insulin-like growth factor 2 / Tumor-induced hypoglycemia / Precision intervention / Neuroendocrine regulation / Tumor metabolism / Hypoglycemia / Non-islet cell tumor hypoglycemia / Hypoglycemia due to islet cell tumor

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Hu Guangqiang, Han Yun, Chen Li, Yan Ke. Pathological mechanisms and therapeutic advances of tumor-associated hypoglycemia: from clinical challenges to precision intervention[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2026, 13(1): 155-163 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.01.021

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