Ketone Ester Treatment Improves Heart Function in Type 2 Diabetes and HFpEF, New Study Finds

"Positive data from oral ketone ester treatment trials support the use of modulating circulating ketone levels in patients with type 2 diabetes and HFpEF," the researchers wrote in Circulation.

Heart failure with preserved ejection fraction significantly contributes to morbidity and mortality in patients with type 2 diabetes. While acute rises in the ketone body 3-hydroxybutyrate have shown beneficial hemodynamic effects in patients without T2DM who have chronic heart failure with reduced ejection fraction, the impact of extended oral ketone ester treatment on cardiovascular health in individuals with T2DM and HFpEF is still not well understood.

To fill this knowledge gap, Nigopan Gopalasingam, Department of Cardiology, Aarhus University Hospital, Denmark, and colleagues conducted a 6-week randomized, double-blind crossover study comprising 24 patients with T2DM and HFpEF.

All participants received a two-week course of KE treatment (25 g of D-ß-hydroxybutyrate-(R)-1,3-butanediol taken four times daily) along with an isocaloric and isovolumic placebo, with a two-week washout period in between. At the end of each treatment phase, patients underwent right heart catheterization, echocardiography, and blood sampling at trough levels of the intervention. Following this, during a 4-hour resting period after a single dose, a second dose was administered, and an exercise test was conducted. The study's primary endpoint was cardiac output measured during the 4-hour rest period.

The researchers reported the following findings:

• During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L) compared with placebo (91±55 µmol/L).
• Compared with placebo, KE treatment increased cardiac output by 0.2 L/min during the 4 hours and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg and at peak exercise by 5 mm Hg.
• KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise and increased stroke volume by 10 mL at peak exercise.
• KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance.
• Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs.

The study showed that a two-week oral ketone ester (KE) treatment resulted in increased cardiac output and reductions in cardiac filling pressures and ventricular stiffness in patients with T2DM and HFpEF. During peak exercise, KE treatment significantly lowered pulmonary capillary wedge pressure and enhanced the pressure-flow relationship.

"These findings suggest that modulating circulating ketone levels could offer a promising new treatment approach for individuals with T2DM and HFpEF," the researchers concluded.

Reference:

https://doi.org/10.1161/CIRCULATIONAHA.124.069732