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Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive
So Ra Kim1,2, Byung-Wan Lee1,2
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
International Journal of Molecular Sciences
|July 15, 2026
Summary
Ketone bodies (KBs), like beta-hydroxybutyrate (β-HB), have complex roles in metabolism. Their impact on diabetes progression and diabetic cardiomyopathy is context-dependent, requiring further research.
Area of Science:
- Metabolic biochemistry
- Cardiovascular research
- Endocrinology
Background:
- Circulating ketone bodies (KBs), especially beta-hydroxybutyrate (β-HB), function as both energy sources and signaling molecules.
- β-HB influences pathways related to oxidative stress, inflammation, and mitochondrial health.
- The precise clinical significance of circulating KBs in cardiometabolic diseases is not fully understood.
Purpose of the Study:
- To review current evidence on the role of KBs in glycemic progression and diabetic cardiomyopathy (DCM).
- To explore the conflicting findings regarding KB levels and their association with hyperglycemia and type 2 diabetes.
- To examine the divergent effects of β-HB on cardiac function and remodeling in DCM models.
Main Methods:
- Systematic review of epidemiologic and experimental studies.
- Analysis of research investigating KB levels in relation to hyperglycemia and type 2 diabetes.
- Evaluation of studies examining β-HB's effects on mitochondrial function and cardiac remodeling in DCM.
Main Results:
- Conflicting associations exist between KB levels and the development of hyperglycemia or type 2 diabetes.
- Some studies suggest elevated KBs indicate a favorable metabolic state or compensation, while others link them to worsening glycemia.
- β-HB has shown both beneficial effects (improved mitochondrial function) and detrimental effects (metabolic inflexibility) in DCM models.
Conclusions:
- The metabolic effects of β-HB are highly context-dependent.
- Factors influencing β-HB's impact include concentration, induction method of ketosis, and the individual's metabolic or disease status.
- Further research is needed to determine if β-HB is an adaptive or maladaptive metabolic signal in cardiometabolic disease.
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