Examining the Effect of Exogenous Ketone Supplementation on Glucose Control in Type 2 Diabetes
- Conditions
- Diabetes Mellitus, Type 2
- Interventions
- Dietary Supplement: Exogenous Ketone MonoesterDietary Supplement: Placebo
- Registration Number
- NCT05155410
- Lead Sponsor
- University of British Columbia
- Brief Summary
Ketone bodies are a fuel source and signaling molecule that are produced by the body during prolonged fasting or if an individuals consistently eats a low-carbohydrate "keto" diet. Blood ketones can be used as a source of energy by the body, but they may also act as signals that impact the functioning of different cells in the body. Recently, the availability of ketone supplements that can be taken orally allows for raising blood ketones without having to fast or eat a "keto" diet. The investigators' studies and those of other researchers have shown that ketone supplementation can lower blood sugar without having to make any other dietary changes. Oral ingestion of ketones may therefore be an effective strategy to improve blood sugar control and influence how cells function.
The main objective of this study is to determine if consuming a ketone supplement 3 times per day (before meals) for 14 days lowers blood sugar and impacts how the body's cells function. The results of this study will be used to guide future recommendations on the utility of ketone supplements for improving health in individuals with, or at elevated risk of, type 2 diabetes.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
- Have a type 2 diabetes diagnosis from a physician
- Have stable use of glucose-lowering medications for at least 3 months
- Are a competitively trained endurance athlete
- Are actively attempting to gain or lose weight
- Have a history of mental illness or existing neurological disease(s), cardiovascular events (i.e., heart attack, stroke) in the last 2 years
- Have hypoglycemia, irritable bowel syndrome or inflammatory bowel disease
- Are currently using insulin or SGLT2 inhibitors
- Are using more than 2 classes of glucose-lowering medication
- Are currently following a ketogenic diet or taking ketone supplements
- Are unable to commit for a 29-day trial
- Are unable to follow a controlled diet
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Experimental Exogenous Ketone Monoester Participants will consume 15 g of an active oral exogenous ketone monoester supplement 15 minutes prior to each meal of the day for a 14-day period. Pre-intervention (baseline) and post-intervention measurements will be obtained before and immediately after the 14-day period. All meals will be provided throughout the supplementation period Participants will wear a continuous glucose monitor for the first 10 consecutive days during the supplementation period. Placebo Placebo Participants will consume a flavor-matched placebo drink and undergo the same procedures described in the Experimental Arm
- Primary Outcome Measures
Name Time Method Glucose Control: Change in Fructosamine Day 14 (post-intervention) Change in glucose control (from pre-intervention Day 0) will be quantified by serum fructosamine obtained by fasting blood sample in both conditions.
- Secondary Outcome Measures
Name Time Method Vascular function Day 0 (Pre-intervention) and Day 14 (post-intervention) Vascular function will be assessed by flow mediated dilation of the brachial artery using vascular ultrasound. A cuff will affixed on the forearm, distal to the brachial artery and will be inflated for 5 minutes. Flow mediation dilation will be measured over a 3-minute period following cuff release.
Cognition: N-back test Day 0 (Pre-intervention) and Day 14 (post-intervention) Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inqisit6 Lab (Millisecond). The test will be the n-back test.
Cognition: Digit-symbol substitution test Day 0 (Pre-intervention) and Day 14 (post-intervention) Cognition will be assessed using a customized battery of psychometrically validated tests within the domain of executive functions using the computer-based app Inquisit6 Lab (Millisecond). The test will be the digit-symbol substitution test.
Change from baseline plasma insulin at 14 days Day 0 (Pre-intervention) and Day 14 (post-intervention) Plasma insulin from venous blood samples will be measured using a high-sensitivity human insulin enzyme-like immunosorbent assay (ELISA) run in duplicate.
Change from baseline circulating inflammatory cytokines at 14 days Day 0 (Pre-intervention) and Day 14 (post-intervention) Key inflammatory cytokines including CRP will be quantified by Mesoscale Discovery U-PLEX run in duplicate.
Oxidative Burst Day 0 (Pre-intervention) and Day 14 (post-intervention) LPS-stimulated oxidative burst by immune cells from whole blood will be quantified by flow cytometry
Glycemic Control: 2hr postprandial hyperglycemia Day 1 through to Day 10 Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 2hr postprandial hyperglycemia.
Glycemic Control: 24hr average glucose area under the curve (AUC) Day 1 through to Day 10 Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing 24hr average glucose AUC.
Change from baseline plasma free fatty acids at 14 days Day 0 (Pre-intervention) and Day 14 (post-intervention) Free fatty acids from venous blood samples will be measured by colorimetric assay run in duplicate.
Phagocytosis Day 0 (Pre-intervention) and Day 14 (post-intervention) Phagocytosis of fluorescent-labelled E. coli by immune cells from whole blood will be quantified by flow cytometry
Degranulation Day 0 (Pre-intervention) and Day 14 (post-intervention) Immune cell degranulation will be quantified by enzyme-linked immunosorbent assay run in duplicate (quantifying myeloperoxidase and elastase in whole blood cell culture supernatants).
Glycemic Control: Fasting glucose Day 1 through to Day 10 Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing fasting plasma glucose.
Glycemic Control: Change in Fasting Plasma glucose Day 14 Change in fasting plasma glucose (from pre-intervention Day 0) will be measured by fasting blood sample in both the active and placebo supplement conditions.
Glycemic Control: Glycemic variability Day 1 through to Day 10 Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing glycemic variability.
Glycemic Control: Time in Target Range Day 1 through to Day 10 Glycemic control will be measured by continuous glucose monitoring using the G6 CGM (Dexcom) in both the active and placebo supplement conditions. Glycemic control will be quantified by assessing time in target range.
Glycemic Control: HbA1c Day 0 (pre-intervention) and Day 14 (post-intervention) Glycemic control will be measured by assessing HbA1c using a point-of-care analyzer.
Blood beta-hydroxybutyrate Day 0 (pre-intervention) and Day 14 (post-intervention) Change in fasting blood beta-hydroxybutyrate will be measured using a standard assay.
Immune Cell Phenotyping Day 0 (Pre-intervention) and Day 14 (post-intervention) Phenotyping of macrophages and T cells will be quantified by surface and intracellular staining by flow cytometry.
Complete blood count Day 0 (Pre-intervention) and Day 14 (post-intervention) A 5-part white blood cell differential and complete blood count will be quantified by hematology analyzer.
Lipid Panel Day 0 (pre-intervention) and Day 14 (post-intervention) Lipid panel (total cholesterol, high-density cholesterol, low-density cholesterol, triglycerides, non-HDL cholesterol, cholesterol/HDL ratio) will be measured using a point-of-care analyzer.
Physical activity Day 0 (pre-intervention) to Day 14 (post-intervention) Physical activity will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Sedentary time Day 0 (pre-intervention) to Day 14 (post-intervention) Sedentary time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Waist circumference Day 0 (pre-intervention) and Day 14 (post-intervention) Change in waist circumference will be measures using a measurement tape.
Body weight Day 0 (pre-intervention) and Day 14 (post-intervention) Change in body weight will be measured using a body weight scale.
Blood pressure Day 0 (pre-intervention) and Day 14 (post-intervention) Change in blood pressure will be measured using an automated blood pressure device. Both systolic and diastolic blood pressure will be measured.
Sleeping time Day 0 (pre-intervention) to Day 14 (post-intervention) Sleeping time will be assessed using an accelerometer (activePal) worn throughout the entire intervention period.
Resting heart rate Day 0 (pre-intervention) and Day 14 (post-intervention) Change resting heart rate will be measured using an automated heart rate monitor device.
Trial Locations
- Locations (1)
University of British Columbia Okanagan
🇨🇦Kelowna, British Columbia, Canada