The effect of a ketone drink on blood glucose levels in people with type 2 diabetes
| ISRCTN | ISRCTN45497544 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN45497544 |
| ClinicalTrials.gov number | NCT06324669 |
| Secondary identifying numbers | 4765060 |
- Submission date
- 16/02/2024
- Registration date
- 19/02/2024
- Last edited
- 28/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Ketones are naturally produced by our body and can affect our blood sugar levels. Ketones could be important in the treatment of type 2 diabetes (T2D). The purpose of this research is to determine if a ketone drink can lower blood sugar in people with T2D following a meal. This research will provide new knowledge about the regulation of blood sugar. This may also inform if ketone drinks could be used as a treatment for T2D.
Who can participate?
We are inviting 12 adults between the ages of 41 and 70 with T2D to take part.
What does the study involve?
The study involves:
A short telephone call with the researcher
A screening visit with a questionnaire and a blood sample
Two ‘priming visits’ to our laboratory to ingest a ‘labelled water’ drink, each followed by a ‘test visit’ the next day
Eating a meal on the day before the test visits
Skipping breakfast before your test visits
Resting on a bed for 13 hours on each test visit when a small amount of glucose (sugar) will be infused into the arm and regular blood samples will be taken
Consuming 2 ketone drinks on one of the test visits
Consuming 2 milkshakes on both of the test visits
What are the possible benefits and risks of participating?
We cannot promise any specific benefits to participants personally. At the end of the study, participants can request results about how their body responded to the ketone drink. The ketone drink is commercially available so there may be financial benefit to companies that sell ketones in the future.
The risks involved in this study are minimal. We will not ask participants to change any of their usual treatment or care. If we find any results that could indicate a previously undiagnosed disease or illness, we will tell participants and advise them to speak to their GP. The ketone drink is commercially available (https://www.deltagketones.com) and has been given to people with type 2 diabetes before with no side effects. Participants will skip breakfast on each of the test days so may feel hungry for a few hours. The milkshake we give after 2.5 hours of the visit should stop them feeling hungry for the next 4.5 hours of the visit until they receive another milkshake. We will give them something to eat and drink before they go home. Insertion of needles may cause some temporary discomfort. The investigators are trained and experienced in all aspects of these procedures. Any concerns that participants may have about any of the procedures will be addressed in full by the researchers prior to participants giving their consent to participate.
Where is the study run from?
Nutritional Physiology Research Unit, St Luke's Campus, University of Exeter, Exeter, UK.
When is the study starting and how long is it expected to run for?
November 2023 to January 2026
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Professor Francis Stephens, F.B.Stephens@exeter.ac.uk
Dr George Pavis, G.Pavis@exeter.ac.uk
Contact information
Public, Scientific, Principal Investigator
University of Exeter
Exeter
EX1 2LU
United Kingdom
 ORCID ID |
0000-0001-6312-5351 |
|---|---|
| Phone | +44 1392722157 |
| f.b.stephens@exeter.ac.uk |
Public, Scientific
University of Exeter
Exeter
EX1 2LU
United Kingdom
| ORCID ID |
0000-0002-3054-5031 |
|---|---|
| Phone | +44 1392725906 |
| g.pavis@exeter.ac.uk |
Study information
| Study design | Single-centre interventional randomized single-blind placebo-controlled crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Laboratory |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Investigating the blood glucose lowering effect of exogenous ketone ingestion in people with type 2 diabetes |
| Study hypothesis | It is hypothesised that the antilipolytic effect of β-hydroxybutyrate reduces endogenous glucose production and/or increases glucose clearance |
| Ethics approval(s) |
Approved 21/11/2023, FHLS Sports and Health Sciences Ethics Committee (University of Exeter, Exeter, EX1 2LU, United Kingdom; +44 300 555 0444; cgr-reg@exeter.ac.uk), ref: 4765060 |
| Condition | Type 2 diabetes |
| Intervention | Participants will visit the laboratory for baseline screening to assess their eligibility. Thereafter they will undergo 2 trials, with trial order (ketone or placebo) randomised using excel ‘rand’ function. On day 1 participants will visit the laboratory to consume ‘heavy water’ (deuterium oxide). On day 2 participants will return and undergo a 13 h test day. After placement of cannulas and the initation of stable isotope tracer infusion, participants will receive a 100 mL flavoured drink containing 0.3 g/kg ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate; ΔG®, University of Oxford; https://www.deltagketones.com) or maltodextrin placebo with stevia and bitter agent to flavour match. The ketone ester is commercially available, is not contraindicated for diabetes medication, the dose is within the guidelines, and it has been used several times before in patients with type 2 diabetes. Participants will then consume a mixed macronutrient study beverage (Ensure Plus, Abbott Nutrition), and have blood samples taken at regular intervals for 4 h. Participants will receive a second dose of their allocated condition (ketone or placebo), consume a second mixed macronutrient beverage, and have blood samples taken for a second 4 h period. |
| Intervention type | Supplement |
| Primary outcome measure | Rate of endogenous glucose production over 4 hours in response to a meal measured by blood sample |
| Secondary outcome measures | 1. Total rate of glucose appearance measured using the change in glucose enrichment/concentration over 4 and 8 hours following a meal 2. Exogenous rate of glucose appearance measured using the change in glucose enrichment/concentration over 4 and 8 hours following a meal 3. Total rate of glucose disappearance measured using the change in glucose enrichment/concentration over 4 and 8 hours following a meal 4. Rate of gluconeogenesis measured using the change in glucose enrichment/concentration over 4 and 8 hours following a meal 5. Rate of glycogenolysis measured using the change in glucose enrichment/concentration over 4 and 8 hours following a meal 6. Beta-cell function using dynamic modelling of insulin/c-peptide secretion over 4 and 8 hours following a meal 7. Insulin concentration using ELISA assay over 4 and 8 hours following a meal 8. glucagon concentration using ELISA assay over 4 and 8 hours following a meal 9. GLP-1 using ELISA assay over 4 and 8 hours following a meal 10. GIP concentration using ELISA assay over 4 and 8 hours following a meal 11. Glycerol concentration using colorimetric assay over 4 and 8 hours following a meal 12. Free fatty acids using colorimetric assay over 4 and 8 hours following a meal 13. Ketone concentration using colorimetric assay over 4 and 8 hours following a meal 13. Energy expenditure using indirect calorimetry over 4 and 8 hours following a meal |
| Overall study start date | 21/11/2023 |
| Overall study end date | 31/01/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 41 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | 12 |
| Total final enrolment | 15 |
| Participant inclusion criteria | 1. Aged 41-70 years old 2. Body mass index 27-40 mg/m² 3. Type 2 diagnosis for more than 1 year 4. HbA1c >6% |
| Participant exclusion criteria | 1. Currently following ketogenic diet 2. Use of insulin 3. HbA1c >10% 4. Recent weight loss (>5kg in 6 months) 5. Recent eGFR <30mL/min 6. Heart failure 7. Substance abuse 8. Cancer 9. Myocardial infarction within 6 months 10. Pregnancy or consideration of 11. Use of antipsychotic drugs |
| Recruitment start date | 15/03/2024 |
| Recruitment end date | 28/01/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Exeter
EX4 4PY
United Kingdom
Sponsor information
University/education
Stocker Road
Exeter
EX4 4PY
England
United Kingdom
| Phone | +44 (0)1392 661000 |
|---|---|
| sid@exeter.ac.uk | |
| Website | http://www.exeter.ac.uk/ |
"ROR" |
https://ror.org/03yghzc09 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/01/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The anonymised datasets generated during and/or analysed during the current study will be stored in an institutional and/or publicly available repository, such as FigShare |
Editorial Notes
28/01/2025: The recruitment end date was changed from 31/08/2025 to 28/01/2025.
22/03/2024: ClinicalTrials.gov number added.
15/03/2024: Internal review.
16/02/2024: Trial's existence confirmed by FHLS Sports and Health Sciences Ethics Committee.
