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

Study Overview
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Brief Summary
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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.

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

Conditions
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Type 2 Diabetes, Ketoses, Metabolic

Intervention / Treatment
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* Dietary Supplement: 3-hydroxybutyrate


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |