Exogenous Ketones in Type 2 Diabetes

The Effect of Acute Exogenous Oral Ketone Supplementation on Blood Glucose Levels in Type 2 Diabetes

Exogenous ketone supplements are proposed to have glucose-lowering potential, provide an alternative fuel for the brain and to enhance cognitive function. No studies have tested whether exogenous ketones can lower blood glucose in people with type 2 diabetes. In addition, the impact of exogenous ketones on brain blood flow, cognitive function or brain-derived neurotrophic factor in humans is unknown. The purpose of this study is to determine if acutely ingesting exogenous ketones, in the form of a ketone monoester drink, can lower glucose and improve measures of brain/cognitive function in humans with type 2 diabetes. Participants will consume a ketone monoester drink or placebo with blood samples, brain blood flow, and cognitive function assessed over 180 minutes. The researchers will also test how the ketone monoester drink impacts appetite and measures of inflammation.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Ketosis
• Intervention / Treatment: Dietary supplement: Ketone monoester; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1V 1V7
      • University of British Columbia, Okanagan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• physician-diagnosed type 2 diabetes of ≥1 year
• current hemoglobin A1C (HbA1c) of 6.5-8.0%
• treatment with lifestyle or stable (≥3 months) oral glucose-lowering medications
• blood pressure of <160/99 mm Hg assessed according to guidelines
• non-smoking
• no prior history of cardiovascular disease or stroke
• not on hormone replacement therapy, corticosteroids, or anti-inflammatory medications
• 20-75 years old

Exclusion Criteria:

• being a competitive endurance athlete
• taking exogenous insulin or sodium glucose transporter 2 (SGLT2) inhibitors
• following a ketogenic diet, low-calorie diet, periodic fasting regimen, or consume ketogenic supplements
• being unable to travel to and from the university
• being unable to follow the controlled diet instructions
• being pregnant or planning to become pregnant during the study (if female)
• disorders of fat metabolism, chronic pancreatitis, had gastric bypass surgery and/or gallbladder disease
• being unable to read or communicate in English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketone monoester; Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight)	Dietary supplement: Ketone monoester; Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.
Placebo Comparator: Placebo; Acute dose of flavour-matched placebo.	Dietary supplement: Placebo; Acute ingestion of taste-matched placebo prior to assessment of outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose	Plasma glucose concentration after ketone or placebo ingestion	180 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma C-peptide	C-peptide across concentration after ketone or placebo ingestion	180 minutes
Plasma Insulin	Insulin across concentration after ketone or placebo ingestion	180 minutes
Plasma Free Fatty Acids	Non-esterified fatty acid concentration after ketone or placebo ingestion	180 minutes
Plasma Tumour Necrosis Factor Alpha	Plasma tumour necrosis factor alpha concentration after ketone or placebo ingestion	180 minutes
Plasma Tumour Interleukin-1beta	Plasma tumour interleukin-1beta concentration after ketone or placebo ingestion	180 minutes
Plasma Tumour Interleukin-6	Plasma tumour interleukin-6 concentration after ketone or placebo ingestion	180 minutes
Cerebral Blood Flow	Intracranial blood flow velocity measured by ultrasound	180 minutes
Blood Pressure	Blood pressure measured manually and by Finipres	180 minutes
Cognitive Function	Measures of cognitive function using Brain Baseline battery on an iPad.	180 minutes
Brain-derived Neurotrophic Factor	Brain-derived neurotrophic factor concentrations after ketone or placebo ingestion	180 minutes
Blood Monocytes	Total blood monocytes and monocyte subsets after ketone or placebo ingestion	180 minutes
Self Reported Hunger and Fullness	Self reported hunger and fullness by a 0 to 100 mm Visual Analog Scale (higher scores mean greater hunger or fullness)	180 minutes
Gastrointestinal Symptoms	Gastrointestinal symptom questionnaire scores after ketone or placebo ingestion on a 0 to 100 mm Visual Analog Scale (higher scores mean greater symptoms)	180 minutes
Total Energy Consumed	Total energy consumed in kilocalories in buffet style meal after ketone or placebo ingestion	180 minutes after ketone or placebo ingestion
Monocyte Histone Acetylation	Histone acetylation status of monocytes measured after ketone or placebo ingestion	180 minutes

Collaborators and Investigators

• Sponsor: University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): May 20, 2022
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: H19-02947

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