Keto Drinks as a Meal Primer in Patients With Type 2 Diabetes

3-hydroxybutyrate as a Meal Primer in Patients With Type 2 Diabetes

The main objective of this clinical trial is to study the effects of orally administered ketone drinks containing the ketone body, 3-hydroxybutyrate (3-OHB), just before a meal in patients with type 2 diabetes. Moreover the investigators will compare the effects of two different ketone drinks.

The hypothesis is:

3-OHB as a pre-meal may:

• Lower postprandial blood glucose and lipids.
• Mediate release of intestinal hormones and affect gastric emptying.
• Affect appetite and other subjective measures related to food intake.

The effects of 3-OHB as a pre-meal will be investigated by blood samples, isotopic tracers examinations, paracetamol test, questionnaires and meal test.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Ketoses, Metabolic
• Intervention / Treatment: Dietary supplement: 3-hydroxybutyrate

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Medical research laboratory, Department of endocrinology, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes diagnosis, metformin treated or dietary treated
• HbA1C < 80 mmol/mol
• 25 < BMI < 35
• Written consent

Exclusion Criteria:

• Severe comorbidity
• Treatment with insulin, GLP-1 analogues, SGLT-2-inhibitors or sulfonylureas
• Specific diets, e.g. ketogenic diet
• PI finds the patient not fit (e.g. mental illness, too nervous, unacceptable screening blood tests or other)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketone salt; Na-D/L-3-hydroxybutyrate dissolved in tap water.	Dietary supplement: 3-hydroxybutyrate; Orally administered pre-meal drinks.
Experimental: Ketone ester; (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate	Dietary supplement: 3-hydroxybutyrate; Orally administered pre-meal drinks.
Placebo Comparator: Placebo; Tap water	Dietary supplement: 3-hydroxybutyrate; Orally administered pre-meal drinks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial P-glucose	Incremental area under the curve (iAUC) for P-glucose.	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial free fatty acids (FFA)	Blood samples	3 hours
Differences in circulating concentrations of 3-hydroxybutyrate	Blood samples	3,5 hours
Lipolysis rate	Measures of palmitate flux (palmitate tracer)	3 hours
Glucose kinetics	Glucose tracer examinations	3 hours
Gastric emptying	Paracetamol test	3 hours
Differences in hunger/satiety	Questionnaire for quantifying hunger/satiety on a VAS scale from 1-10	4 hours
Differences in actual hunger	Ad libitum meal test	30 minutes
Differences in circulating concentrations of insulin	Blood samples	3,5 hours
Differences in circulating concentrations of glucagon	Blood samples	3,5 hours
Differences in circulating concentrations of c-peptide	Blood samples	3,5 hours
Differences in circulating concentrations of Glucagon-like peptide-1 (GLP-1)	Blood samples	3,5 hours
Differences in circulating concentrations of Gastric inhibitory polypeptide (GIP)	Blood samples	3,5 hours
Differences in circulating concentrations of ghrelin	Blood samples	3,5 hours
Differences in circulating concentrations of cholecystokinin	Blood samples	3,5 hours
Differences in circulating concentrations of gastrin	Blood samples	3,5 hours

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Director: Niels Møller, Professor, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Acid-Base Imbalance; Acidosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Ketosis
• Other Study ID Numbers: 1-10-72-282-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No