Twenty-four patients with type 2 diabetes and heart failure with preserved ejection fraction completed a 6-week randomized, double-blind crossover study of 2 weeks of ketone ester (25 g D-beta-hydroxybutyrate-(R)-1,3-butanediol four times daily) and 2 weeks of isocaloric placebo, separated by a 2-week washout. During the 4-hour resting period, 3-hydroxybutyrate was 1010 +/- 56 µmol/L after ketone ester versus 91 +/- 55 µmol/L after placebo. Compared with placebo, ketone ester increased cardiac output by 0.2 L/min, decreased pulmonary capillary wedge pressure by 1 mm Hg at rest and by 5 mm Hg at peak exercise, and increased stroke volume by 10 mL at peak exercise.
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