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
Authors' conclusion
Our 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.
Study context
- Population
- Men aged ≥18 years, BMI 19–26 kg/m², no severe comorbidities: ten with T1D and ten healthy controls, after overnight fast10 T1D, 10 controls
- Comparison
- i.v. 3-OHB infusion vs saline, in T1D vs healthy controls
- Primary endpoint
- Palmitate flux (lipolytic rate)
Methodological detailssingle-blind, Participants blinded to allocation; investigators aware of intervention order
- Single-blind
- Participants blinded to allocation; investigators aware of intervention order
Primary result
As reported in the abstract
Lipolytic rate (palmitate flux)
- 3-OHB suppressed lipolytic rates by >50% vs NaCl in both T1D and control participants
- 3-OHB vs NaCl: P < 0.001
Further findings
Blood D/L-3-OHB concentration during 3-OHB infusion
P = 0.03
- Circulating NEFA · reduced by ≈0.5 mmol/l in both T1D and controls
- P < 0.001
Circulating NEFA
- NEFA reduced by ≈0.5 mmol/l with 3-OHB vs NaCl
Adipose tissue signalling
- Reduced protein kinase A phosphorylation of perilipin, similarly in T1D and controls
- P < 0.001
- Reduced hormone-sensitive lipase phosphorylation at Ser660
- P < 0.001
- Reduced hormone-sensitive lipase phosphorylation at Ser563
- P < 0.01
Glucose metabolism
- Indices of glucose metabolism unaffected in both groups
Original publication
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. Diabetologia. Published 10 April 2025. doi:10.
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