Ketone monoester ingestion improves cardiac function in adults with type 2 diabetes: a double-blind, placebo controlled, randomised, crossover trial.

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 (Q̇i). Secondary aims were to assess the effects of K_me 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 K_me (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. K_me ingestion raised circulating β-Hb throughout the protocol (peak 1.9 mM; P=0.001 vs. placebo). K_me 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 K_me and placebo in heart rate (P=0.995), FMD (P=0.542), ACh max (P=0.800), insulin max (P=0.242). Ingestion of K_me improved Q̇i, stroke volume index and peripheral muscle oxygenation, but did not alter macro- or microvascular endothelial function in people with T2D.