Trial reportDiabetologia2025
Metabolic effects of 3-hydroxybutyrate infusion in individuals with type 1 diabetes compared with healthy control participants: a randomised crossover trial showing intact feedback suppression of lipolysis.
Trial report in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04656236 (Metabolic Effects of Exogenous 3-hydroxybutyrate in Patients With Type 1 Diabetes and Healthy Controls), which is not on this map. Not yet cited in PubMed.
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Metabolic Effects of Exogenous 3-hydroxybutyrate in Patients With Type 1 Diabetes and Healthy Controls
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7 authors.
Funding
Abstract
aims/hypothesisDiabetic ketoacidosis remains a severe complication in type 1 diabetes, arising from insufficient insulin levels and accelerated lipolytic rate, leading to increased β-oxidation of NEFA and ketone body production in the liver. The ketone body 3-hydroxybutyrate (3-OHB) inhibits lipolysis in healthy individuals. The current study aimed to test whether this feedback suppression of lipolysis by 3-OHB is disrupted in individuals with type 1 diabetes.
methodsWe used a single-blind, randomised, crossover design to study ten men diagnosed with type 1 diabetes and ten healthy control participants. Eligibility criteria were male sex, age ≥18 years, BMI of 19-26 kg/m
resultsDuring the infusion of 3-OHB, the D/L-3-OHB blood concentrations increased to 3.3 ± 0.7 mmol/l in participants with type 1 diabetes compared with 2.9 ± 0.5 mmol/l in control participants (p=0.03). The infusion effectively suppressed the lipolytic rates by more than 50% (p<0.001) and reduced circulating NEFA by approximately 0.5 mmol/l (p<0.001) compared with NaCl in both participants with type 1 diabetes and control participants. In adipose tissue, 3-OHB reduced protein kinase A phosphorylation of perilipin (p<0.001) and hormone-sensitive lipase phosphorylation at Ser660 (p<0.001) and Ser563 (p<0.01) similarly in participants with type 1 diabetes and control participants. Indices of glucose metabolism remained unaffected throughout in both groups. CONCLUSIONS/
interpretationOur findings indicate that, in individuals with type 1 diabetes, the suppression of lipolysis, blood NEFA concentrations and adipose tissue signalling activity in response to 3-OHB remains intact compared with healthy control participants. These findings imply that derailment of receptor signalling by 3-OHB is unlikely to be involved in the development of diabetic ketoacidosis.
trial registrationClinicalTrials.gov NCT04656236
fundingOpen access funding provided by Aarhus Universitet. This study was supported by the Novo Nordisk Foundation (NNF19OC0058872) and the Health Research Foundation of Central Denmark Region.
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