Warburg Effect-Associated Non-Insulin-Mediated Hypoglycemia in Chronic Infection

Tilagamaty Murthy; Sharifah Noor Adrilla Long Mohd Noor Affendi; Shazatul Reza Mohd Redzuan; Gayathri Devi Krishnan; Subashini Rajoo

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Warburg Effect-Associated Non-Insulin-Mediated Hypoglycemia in Chronic Infection

Author: Tilagamaty Murthy ¹ ; Sharifah Noor Adrilla Long Mohd Noor Affendi ¹ ; Shazatul Reza Mohd Redzuan ¹ ; Gayathri Devi Krishnan ¹ ; Subashini Rajoo ¹
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1. Endocrine Unit, Department of Internal Medicine, Hospital Kuala Lumpur
Publication Type:Journal Article
MeSH: Persistent Infection; Hypoglycemia
From: Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):67-
CountryPhilippines
Language:English
Abstract: Introduction:The Warburg effect refers to a metabolic shift in which cells preferentially utilize aerobic glycolysis rather than oxidative phosphorylation despite adequate oxygen availability. This phenomenon is increasingly recognized as the mechanism for tumor-associated hypoglycemia, or paraneoplastic syndromes such as insulin-like growth factor-2 (IGF-2)– mediated non-islet cell tumor hypoglycemia. We present a case of Warburg effect with management challenges.
Case:A 47-year-old male with advanced, treatment-naive retroviral disease presented with chronic cough, progressive right thigh swelling, constitutional symptoms over several months, followed by reduced responsiveness for 2 days prior to admission. Clinically, he was delirious, cachectic with generalized lung crepitations and right thigh mass. He was diagnosed with smear-negative disseminated tuberculosis, and thigh mass was considered either a tuberculous granuloma or sarcoma. During hospitalization, he developed recurrent hypoglycemia with lactatemia despite intravenous dextrose, optimized enteral feeding and a 1-day course of intravenous octreotide. His blood investigations showed full blood count, renal function test, liver function test, and serum ketone within normal range. His arterial blood gas analysis showed type B lactic acidosis with persistent lactatemia. At the time of hypoglycemia (RBS: 3.1 mmol/L), his serum insulin was suppressed, C-peptide was low–normal, morning cortisol was elevated, and IGF-1 was markedly reduced suggestive of non-insulin-mediated hypoglycemia secondary to Warburg effect.
Conclusion:In patients with retroviral disease and tuberculosis, Warburg effect may lead to poorer clinical outcomes and management may be challenging. Thus, definitive antimicrobial therapy with second generation somatostatin analogues (Pasireotide) may be considered in selected cases to modulate dysregulated hormonal and metabolic pathways. Early identification and timely targeted intervention are crucial to improving outcomes in this high-risk population.
Full text:2026080316504502619EP_A087.pdf