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The cardiac and hemodynamic effects of ketone bodies are abnormalin patients with type 1 diabetes: a randomized controlled trial

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posted on 2025-06-17, 16:23 authored by Kristoffer Berg-Hansen, Maj Bangshaab, Nigopan Gopalasingam, Roni Nielsen, Mads Svart, Nikolaj Rittig, Niels Møller, Henrik Wiggers

Impaired cardiac ketone oxidative capacity is a possible disease mechanism in the development of diabetic cardiomyopathy. We examined whether the cardiovascular effects of ketone bodies are different in patients with type 1 diabetes (T1D) compared with healthy controls.

Nine patients with T1D and eight age-matched healthy controls were randomized in a single-blind crossover design to receive a three-hour infusion of 3-hydroxybutyrate (3-OHB) or tonicity-matched saline in random order, separated by a one-hour washout period. Assessor-blinded echocardiographic evaluation of cardiovascular function was performed at baseline and following 150 minutes of each intervention.

Circulating 3-OHB increased during 3-OHB infusion vs. placebo in healthy controls, with a similar increase in patients with T1D. In healthy controls, 3-OHB infusion increased cardiac output by 1.9±0.4 L/min but only by 0.5±0.1 L/min in patients with T1D. Stroke volume increased by 14±5 mL and left ventricular (LV) ejection fraction by 3±1 percentage points in healthy controls with no change in patients with T1D. During 3-OHB infusion in patients with T1D, LV global wasted work increased and LV global work efficiency decreased. In conclusion, patients with T1D displayed an abnormal cardiovascular response to 3-OHB infusion. Diabetic cardiomyopathy in patients may involve impaired cardiac ketone metabolism.

Funding

This study was supported by the The Independent Research Fund Denmark (0134-00043B), The Danish Heart Foundation (19-R135-A9280-22126), the Novo Nordisk Foundation (NNF17OC0028230), the Arvid Nilsson Foundation and Ellen and Ivan Osiiers Legat.

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