Introduction and Objective: Heart Failure (HF) in T2D is common and increases mortality. IV Ketone infusion improves EF% ~6% at 3hrs in patients with T2D and HFrEF. Oral ketones (OKE) have shown similar results. Here, we evaluate the effect of chronic OKE administration (7 days) on cardiac efficiency. Methods: 12 subjects with T2D and HFrEF underwent cardiac MRI and metabolic testing at baseline, 3 hours after a single OKE dose, and after 7 days of twice-daily OKE administration. Results: Participants (BMI 31±1kg/m², HbA1c 7.1±0.3, EF 42±2%) ingested OKE, which rapidly raised blood ketones to 6.0±0.3mmol/L at 3hrs with an increase in EF=5.9±0.9%. This effect continued after 7 days. Interestingly, we observed an increase in c-peptide and insulin. This intriguing paradox further suggests that ketone bodies have insulinogenic properties that may have therapeutic potential. Further studies will aim to disentangle the effects of ketones, both as an alternative fuel source and as a signaling metabolite. Conclusion: Chronic administration of OKE is safe and has been shown to improve cardiac efficiency, which appears to be dose-dependent. We have yet to explore whether these effects can be extended in the long term, and interestingly, elevated KE exhibit insulinogenic properties that warrant further exploration. Disclosure F.M. Acosta: None. S. Chidurala: None. A. Moody: None. P.F. Frausto Lerma: None. B. Hu: None. C. Rollins: None. D. Juarez: None. M. Escobar Vasco: Speaker's Bureau; Current; Eli Lilly and Company. G.D. Clarke: None. C.D. Solis-Herrera: Research Support; Current; Abbott Diabetes. Speaker's Bureau; Current; Bayer AG. Research Support; Current; Novartis Pharmaceuticals Corporation, Bayer AG. Speaker's Bureau; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Funding UTHSCSA IIMS/CTSA Pilot Funding
Acosta et al. (Sun,) studied this question.