Perissiou M, Saynor Z L, Feka K, Edwards C, James T J, Corbett J, Mayes H, Shute J, Cummings M, Black M I, Strain W D, Little J P, Shepherd A I
Physical Activity, Health and Rehabilitation Thematic Research Group, School of Psychology, Sport & Health Sciences, Faculty of Science and Health, University of Portsmouth, Portsmouth, United Kingdom.
School of Health Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom.
J Appl Physiol (1985). 2025 Feb 1;138(2):546-558. doi: 10.1152/japplphysiol.00800.2024. Epub 2025 Jan 17.
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) ingestion on cardiac output index ([Formula: see text]i). The secondary aims were to assess the effects of K 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] with T2D. Participants completed two conditions, where they ingested a K (0.115 g·kg) 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 ingestion raised circulating β-Hb throughout the protocol (peak 1.9 mM; = 0.001 vs. placebo). K ingestion increased [Formula: see text]i by 0.75 ± 0.5 L·min·m ( = 0.003), stroke volume index by 7.2 ± 4.5 mL·m ( = 0.001), and peripheral muscle oxygenation by 9.9 ± 7.1% ( = 0.001) and reduced systemic vascular resistance index by -420 ± -225 dyn·s·cm·m ( = 0.031) compared with the placebo condition. There were no differences between K and placebo in heart rate ( = 0.995), FMD ( = 0.542), ACh max ( = 0.800), and insulin max ( = 0.242). Ingestion of K improved [Formula: see text], stroke volume index, and peripheral muscle oxygenation but did not alter macro- or microvascular endothelial function in people with T2D. For the first time, we show that acute ketone monoester ingestion (K) 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 ingestion improves peripheral skeletal muscle oxygenation during moderate intensity and maximal exercise. K has no effect on macro- or microvascular endothelial function in people with type 2 diabetes.
2型糖尿病（T2D）是一种与心血管功能障碍相关的代谢性疾病。心肌优先使用酮类而非游离脂肪酸作为更节能的底物。主要目的是评估摄入酮单酯（K）对心输出量指数（[公式：见正文]i）的影响。次要目的是评估摄入K对静息、递增式骑行期间及之后心脏血流动力学、肌肉氧合和血管功能标志物的影响。我们对13名患有T2D的成年人[年龄，66±10岁；体重指数（BMI），31.3±7.0kg·m²]进行了一项双盲、随机、交叉设计研究。参与者完成两种情况，即分别摄入K（0.115g·kg）或口味匹配的安慰剂饮料。使用胸阻抗心动图测量心脏功能，通过近红外光谱法测定小腿肌肉的氧合情况。通过血流介导的血管舒张（FMD）测量大血管内皮功能，通过乙酰胆碱（ACh）和胰岛素的经皮递送测量微血管内皮功能。全程测量循环中的β-羟基丁酸酯[β-Hb]。在整个实验过程中，摄入K使循环中的β-Hb升高（峰值为1.9mM；与安慰剂相比，P = 0.001）。与安慰剂组相比，摄入K使[公式：见正文]i增加0.75±0.5L·min⁻¹·m⁻²（P = 0.003），每搏输出量指数增加7.2±4.5mL·m⁻²（P = 0.001），外周肌肉氧合增加9.9±7.1%（P = 0.001），全身血管阻力指数降低-420±-225dyn·s·cm⁻⁵·m⁻²（P = 0.031）。K组与安慰剂组在心率（P = 0.995）、FMD（P = 0.542）、ACh最大值（P = 0.800）和胰岛素最大值（P = 0.242）方面无差异。摄入K改善了[公式：见正文]、每搏输出量指数和外周肌肉氧合，但未改变T2D患者的大血管或微血管内皮功能。我们首次表明，在未使用钠葡萄糖转运体抑制剂（即无药物诱导的酮症）的2型糖尿病患者中，急性摄入酮单酯（K）可在静息和运动期间增加心输出量和每搏输出量，并降低全身血管阻力。急性摄入K可改善中等强度和最大运动期间外周骨骼肌的氧合情况。K对2型糖尿病患者的大血管或微血管内皮功能无影响。
