M., Perissiou, Saynor, Z.L., Feka, K., James, T.J., Corbett, J., Mayes, H., Shute, J., Cummings, M., Black, M.I., Strain, W.D., Little, J.P. and Shepherd, A.I. (2025) Ketone monoester ingestion improves cardiac function in adults with type 2 diabetes: a double-blind, placebo controlled, randomised, crossover trial. Journal of Applied Physiology, 138 (2), 546-558. (doi:10.1152/japplphysiol.00800.2024).
Abstract
Type 2 diabetes (T2D) is a metabolic disease associated with cardiovascular dysfunction. The myocardium preferentially uses ketones over free fatty acids as a more energy efficient substrate. The primary aim was to assess the effects of ketone monoester (Kme) ingestion on cardiac output index (Q̇i). Secondary aims were to assess the effects of Kme ingestion on markers of cardiac haemodynamics, muscle oxygenation and vascular function at rest, during and following step-incremental cycling.
We undertook a double-blind, randomised, crossover design study in 13 adults (age, 66±10 y; BMI, 31.3±7.0 kg·m−2) with T2D. Participants completed two conditions, where they ingested a Kme (0.115 g‧kg−1) or a placebo taste-mathced drink. Cardiac function was measured using thoracic impedance cardiography and muscle oxygenation of the calf was determined via near-infrared spectroscopy. Macrovascular endothelial function was measured by flow mediated dilation (FMD) and microvascular endothelial function was measured via transdermal delivery of acetylcholine (ACh) and insulin. Circulating β-hydroxybutyrate [β-Hb] was measured throughout.
Kme ingestion raised circulating β-Hb throughout the protocol (peak 1.9 mM; P=0.001 vs. placebo). Kme ingestion increased Q̇i by 0.75±0.5 L∙min−1∙m−2 (P=0.003) stroke volume index by 7.2±4.5 mL∙m−2 (P=0.001), and peripheral muscle oxygenation by 9.9±7.1% (P=0.001) and reduced systemic vascular resistance index by-420±-225 dyn∙s−1∙cm−5∙m−2 (P=0.031) compared to placebo condition. There were no differences between Kme and placebo in heart rate (P=0.995), FMD (P=0.542), ACh max (P=0.800), insulin max (P=0.242).
Ingestion of Kme improved Q̇i, stroke volume index and peripheral muscle oxygenation, but did not alter macro- or microvascular endothelial function in people with T2D.
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