Ketone monoester ingestion improves cardiac function in adults with type 2 diabetes: a double-blind,...

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 (K_me) ingestion on cardiac output index ([Formula: see text]i). The secondary aims were to assess the effects of K_me ingestion on markers of cardiac hemodynamics, muscle oxygenation, and vascular function at rest, during and following step-incremental cycling. We undertook a double-blind, randomized, crossover design study in 13 adults [age, 66 ± 10 yr; body mass index (BMI), 31.3 ± 7.0 kg·m^-2] with T2D. Participants completed two conditions, where they ingested a K_me (0.115 g·kg^-1) or a placebo taste-matched 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. K_me ingestion raised circulating β-Hb throughout the protocol (peak 1.9 mM; P = 0.001 vs. placebo). K_me ingestion increased [Formula: see text]i 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 with the placebo condition. There were no differences between K_me and placebo in heart rate (P = 0.995), FMD (P = 0.542), ACh max (P = 0.800), and insulin max (P = 0.242). Ingestion of K_me improved [Formula: see text], stroke volume index, and peripheral muscle oxygenation but did not alter macro- or microvascular endothelial function in people with T2D.NEW & NOTEWORTHY For the first time, we show that acute ketone monoester ingestion (K_me) can increase cardiac output and stroke volume and reduce systemic vascular resistance at rest and during exercise in sodium glucose transporter inhibitors naïve (i.e. no drug-induced ketosis) people with type 2 diabetes. Acute K_me ingestion improves peripheral skeletal muscle oxygenation during moderate intensity and maximal exercise. K_me has no effect on macro- or microvascular endothelial function in people with type 2 diabetes.