Metabolic reprogramming in diabetes and other endocrine and metabolic disorders: exploring the Warburg effect, ketones, and SGLT2 inhibitors. — CFSMEATLAS
Metabolic reprogramming in diabetes and other endocrine and metabolic disorders: exploring the Warburg effect, ketones, and SGLT2 inhibitors.
Carrera-Bastos, Pedro, Muskiet, Marcel H A, Mata-Ordoñez, Fernando et al. · Reviews in endocrine & metabolic disorders · 2026 · DOI
Quick Summary
This review examines a cellular energy pattern called the Warburg effect, which causes cells to shift from their normal energy-making processes to a different system that prioritizes cell growth over efficient energy production. The authors suggest this pattern occurs not just in cancer, but also in conditions like ME/CFS, diabetes, and other chronic diseases. They explore whether treatments like fasting, special diets, ketone supplements, and certain diabetes medications might help by reversing this metabolic shift.
Why It Matters
This work offers an alternative mechanistic framework for understanding ME/CFS energy metabolism—proposing that observed 'mitochondrial dysfunction' may be secondary to cellular metabolic reprogramming rather than a primary cause. If accurate, this could redirect research priorities and therapeutic development toward addressing metabolic switching rather than focusing solely on mitochondrial repair, potentially opening new avenues for intervention in ME/CFS.
Observed Findings
The Warburg effect is documented across multiple chronic disorders including type 2 diabetes, heart failure, kidney failure, therapy-refractory epilepsy, Alzheimer's and Parkinson's diseases, ME/CFS, and post-viral syndromes.
Cells exhibiting Warburg-like metabolism show increased glucose and glutamine uptake, elevated intracellular pH and sodium, reduced oxidative stress, altered autophagy, and increased lactate production.
Senescent cells in these disorders display Warburg-like metabolism with cell cycle arrest and enhanced anabolic activity.
Interventions examined include intermittent fasting, ketogenic diets, ketone supplements, and sodium/glucose co-transporter 2 inhibitors as potential modulators of this metabolic state.
Inferred Conclusions
The Warburg effect represents a common metabolic adaptation across diverse chronic diseases, suggesting a unifying mechanistic framework.
The 'energy deficit' in these conditions may reflect metabolic reprogramming prioritizing biomass production over energy efficiency, rather than primary mitochondrial failure.
Therapeutic interventions targeting metabolic switching may offer disease-modifying potential across multiple chronic conditions including ME/CFS.
Remaining Questions
Does metabolic switching drive disease pathology in ME/CFS, or is it a consequence of other primary pathogenic mechanisms?
What This Study Does Not Prove
This review does not establish causation or prove that the Warburg effect is the primary driver of ME/CFS pathology; it presents a hypothesis synthesizing existing literature. The abstract does not provide evidence from controlled trials in ME/CFS patients, so direct efficacy of proposed interventions (fasting, ketogenic diet, SGLT2 inhibitors) specifically in ME/CFS remains unproven. Correlation between Warburg-like metabolism and disease presence does not exclude other concurrent pathogenic mechanisms.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Which interventions (fasting, ketogenic diet, ketones, SGLT2 inhibitors) most effectively reverse Warburg-like metabolism in ME/CFS specifically, and in what patient subgroups?
Can reversal of the Warburg effect phenotype produce sustained clinical improvement in ME/CFS symptoms and biomarkers?
What triggers initial metabolic reprogramming in ME/CFS, particularly in post-viral presentations?