896-P: Positive Effect of Acute and Chronic Effects of Oral Ketones in Subjects with HFrEF and Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 74; no. Supplement_1; p. 1
• Main Authors: ACOSTA, FRANCISCA M., CHIDURALA, SUCHIT, FRAUSTO, PAOLA, MARQUEZ NAJERA, GUILLERMO, MOODY, ALEXANDER, TODD, BYRON, HU, BEVERLY, ROLLINS, CAITLYN, JUAREZ, DEANNA, ESCOBAR VASCO, MARIA, CLARKE, GEOFFREY D., SOLIS-HERRERA, CAROLINA
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 20.06.2025
• Subjects: Blood levels; Cardiac muscle; Chronic effects; Diabetes mellitus; Dosage; Energy resources; Ketones; Skeletal muscle
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db25-896-P

Introduction and Objective: Ketones are energy substrates, serving as a "superfuel" for the heart, skeletal muscle, etc.. Our previous work showed that 3-hour intravenous (IV) exogenous ketones (KE) improved left ventricular function in T2D patients with HFrEF by up to 6%, dose-dependently. However, IV delivery is invasive and impractical for daily use. This study explores acute (3-hour) and chronic (1-week) effects of oral ketones on heart function in T2D patients with HFrEF. Methods: 8 participants with T2D (BMI 23-38 kg/m², HbA1c 6.0-10.0%, eGFR ≥30 ml/min/1.73m², EF <50%) were included. Baseline assessments included a 6-minute walk test (6MWT) and PROMIS Physical Function (PPF) survey. In the acute study, participants consumed two doses of DeltaG-ketone monoester 90 mins. apart. Cardiac MRIs and blood tests were performed pre- and post-dosing. In the chronic study, participants repeated daily ketone dosing for 7 days, with final assessments on day 8. Results: Blood ketone levels significantly increased during the acute phase, peaking at 6±0.3 mmol/L after 3 hours (p<0.0001), without significant changes in glucose (p=0.23). Ejection fraction (EF%) improved significantly during the acute phase (5.0±1.3%) and after 7 days of daily dosing (4.9.±0.6%). Conclusion: Oral KE ingestion shows promise as an adjunct therapy for T2D patients with HFrEF, potentially reducing acute HF admissions and improving mortality. Larger studies are needed to validate these findings.