Summary: In adults with type 1 diabetes, a randomized controlled crossover trial found that the cardiac output response to intravenous 3-hydroxybutyrate was blunted by roughly 80% compared with healthy controls. Systolic function did not improve and left ventricular work efficiency was reduced, consistent with impaired cardiac ketone metabolism rather than a beneficial haemodynamic effect.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with type 1 diabetes compared with healthy control participants; randomized controlled crossover design (single-centre, Denmark). |
| Intervention | Intravenous 3-hydroxybutyrate (ketone body) infusion, with cardiac and haemodynamic responses measured against a control infusion in a crossover fashion. |
| Comparison | Healthy control participants without diabetes undergoing the same 3-hydroxybutyrate infusion protocol; within-trial control infusion served as the internal comparator. |
| Outcome | The cardiac output response to 3-hydroxybutyrate was blunted by approximately 80% in type 1 diabetes relative to controls. Systolic function did not improve and left ventricular work efficiency was reduced. The abstract reports directional effects without published 95% confidence intervals or p-values; no ARR or NNT applies to this physiological endpoint study. |
Expert Commentary
This mechanistic crossover trial offers a clean physiological signal: the heart in type 1 diabetes responds poorly to an acute ketone load, with the cardiac output response cut by roughly 80% and no improvement in systolic function. The verdict is that ketone bodies are handled abnormally by the diabetic heart, which fits the wider hypothesis that impaired ketone utilisation contributes to diabetic cardiomyopathy. The crossover design strengthens internal comparison, and the absence of declared industry or manufacturer sponsorship is reassuring for an infusion study. The central limitation is scope. This is a small, acute, single-centre physiological experiment measuring haemodynamic surrogates over minutes, not clinical outcomes over years, so it cannot tell us whether correcting ketone handling changes heart failure or mortality. The published abstract also reports effects directionally without confidence intervals, so the precision of the 80% figure should be read cautiously until the full data are examined. Can I use this with my patients? Not yet in any therapeutic sense; there is nothing here to prescribe or withhold for a person with type 1 diabetes. What it does offer is mechanistic context for why the diabetic heart may be energetically vulnerable. I would like to see larger studies linking this blunted response to measurable cardiac structure and event rates before it informs care.
References
Berg-Hansen K, Bangshaab M, Gopalasingam N, Nielsen R, Svart M, Rittig N, Møller N, Wiggers H. The Cardiac and Hemodynamic Effects of Ketone Bodies Are Abnormal in Patients With Type 1 Diabetes: A Randomized Controlled Trial. Diabetes. 2025;74(9):1643-1651. doi:10.2337/db25-0243