Exogenous Ketones and Glucose Tolerance

Study Overview
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Brief Summary
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The ketone body beta-hydroxybutyrate is produced during prolonged fasting or when endogenous carbohydrate stores are depleted and can be used as an alternative fuel source. Exogenous beta-hydroxybutyrate, in the form of a ketone monoester, is proposed to have glucose-lowering potential but this has not been adequately studied. The purpose of this study is to determine whether supplementing with an acute dose of ketone monoester can improve the glycemic response to an oral glucose tolerance test in individuals with impaired fasting glucose.

Official Title
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The Effect of Exogenous Ketone Monoester Supplement on Glycemic Response to an Oral Glucose Tolerance Test

Conditions
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Ketones, Dietary Supplements

Intervention / Treatment
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* Dietary Supplement: Ketone monoester
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Not taking any medications affecting glucose metabolism. Elevated fasting glucose level (5.6-6.9 mmol/L) OR body mass index >28 kg/m2 OR elevated waist circumference (>102 cm for males, >88 cm for females) Exclusion Criteria: Diagnosed with diabetes. Diagnosed with heart disease. Competitive endurance athlete (self-identified as engaged in specific endurance training in triathlon, cycling, or distance running and competing in races or competition) Recent (last 3 months) or current consumption of a low-carbohydrate ketogenic diet Current consumption of ketone supplements Pregnant or planning to become pregnant during the study (if female)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone monoester<br>Acute morning dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.45 ml/kg body weight) | Dietary Supplement: Ketone monoester<br>* Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior a 2-hour oral glucose tolerance test.<br>|
| Placebo Comparator: Placebo<br>Acute morning dose of flavour-matched placebo. | Dietary Supplement: Placebo<br>* Acute ingestion of a taste-matched placebo prior a 2-hour oral glucose tolerance test.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose area under the curve | Area under the curve for glucose during oral glucose tolerance test | 2-hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin area under the curve | Insulin area under the curve during oral glucose tolerance test | 2-hour | 
| Free fatty acids area under the curve | Non-esterified fatty acids area under the curve during oral glucose tolerance test | 2-hour | 
| Caspase-1 activation | Caspase-1 activation assessed before and after ketone or placebo ingestion in the morning | 15 minutes | 
| Inflammatory cytokines | Inflammatory cytokines assessed before and after ketone or placebo ingestion in the morning | 15 minutes | 
| C-peptide area under the curve | C-peptide area under the curve during oral glucose tolerance test | 2-hour | 
| GLP-1 area under the curve | GLP-1 area under the curve during oral glucose tolerance test | 2-hour | 
| Glucagon area under the curve | Glucagon area under the curve during oral glucose tolerance test | 2-hour | 
| Glucose incremental area under the curve | Incremental area under the curve (above baseline) for glucose during oral glucose tolerance test | 2-hour | 
| Insulin incremental area under the curve | Incremental area under the curve (above baseline) for insulin during oral glucose tolerance test | 2-hour | 
| 2-hr glucose level | Plasma glucose assessed 2-hr after oral glucose tolerance test. | 2-hour | 
| Oral glucose sensitivity index | Oral glucose sensitivity index derived from glucose and insulin values throughout the 2-hr oral glucose tolerance test | 2-hour |