Infusion of 3-hydroxybutyrate increased cardiac output by 1.9 ± 0.4 L/min in healthy controls but only by 0.5 ± 0.1 L/min in patients with type 1 diabetes, showing an impaired cardiac response.
RCT (n=17)
Single-blind
Crossover
Does 3-hydroxybutyrate infusion improve cardiovascular function differently in patients with type 1 diabetes compared to healthy controls?
Patients with type 1 diabetes exhibit a blunted cardiac response to ketone body infusion, suggesting that impaired cardiac ketone metabolism may contribute to diabetic cardiomyopathy.
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 control individuals. In a single-blind study with a crossover design, nine patients with T1D and eight age-matched, healthy control study participants were randomized to receive a 3-h infusion of 3-hydroxybutyrate (3-OHB) or tonicity-matched saline in random order, separated by a 1-h washout period. Assessor-blinded echocardiographic evaluation of cardiovascular function was performed at baseline and after 150 min of each intervention. Circulating 3-OHB increased during 3-OHB infusion versus placebo in healthy control participants, with a similar increase in patients with T1D. In the control group, 3-OHB infusion increased cardiac output by 1.9 ± 0.4 L/min (means ± SE) 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 control participants; there was no change in these parameters 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 had an abnormal cardiovascular response to 3-OHB infusion. Diabetic cardiomyopathy in patients may involve impaired cardiac ketone metabolism. ARTICLE HIGHLIGHTS The diabetic heart has reduced ketone utilization due to impaired ketolytic enzyme activity. In a randomized controlled crossover trial, we investigated whether the cardiac response to 3-hydroxybutyrate infusion is impaired in type 1 diabetes. The response on cardiac output was blunted by 80% in type 1 diabetes, with no improvement in systolic function and left ventricular work efficiency was reduced. These findings suggest impaired cardiac ketone metabolism may have clinical significance and could contribute to diabetic cardiomyopathy.
Berg‐Hansen et al. (Tue,) conducted a rct in Type 1 diabetes (n=17). 3-hydroxybutyrate (3-OHB) vs. Tonicity-matched saline was evaluated on Change in cardiac output. Infusion of 3-hydroxybutyrate increased cardiac output by 1.9 ± 0.4 L/min in healthy controls but only by 0.5 ± 0.1 L/min in patients with type 1 diabetes, showing an impaired cardiac response.
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