Work

Revisiting the thrifty substrate hypothesis: Ketone bodies as cardioprotective fuels in diabetes and SGLT2 inhibitor therapy

Year: 2025

Type: article

Abstract: SGLT2 inhibitors increase circulating β-hydroxybutyrate (β-OH-B), a ketone body that may enhance cardiac efficiency in HFrEF. The "thrifty substrate hypothesis" suggests β-OH-B provides more ATP per oxygen consumed than glucose or fatty acids. Clinical studies by Nielsen et al. and Solis-Herrera et al. show that β-OH-B infusion improves cardiac output, ejection fraction, and myocardial blood flow in HFrEF patients-with and without diabetes-without increasing oxygen demand or reducing glucose uptake. These findings support β-OH-B as an additive metabolic fuel, highlighting the therapeutic potential of enhancing cardiac metabolic flexibility.

Source: Journal of Diabetes Investigation

DOI: 10.1111/jdi.70068

Authors: Yoriyasu Suzuki, Tetsuya Amano

Institution: Aichi Medical University

Language: English

Topic: Cardiovascular Function and Risk Factors

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,850