Diabetes Mellitus Risk, Hyperglycemia, Postprandial, Overweight and Obesity
Conditions
Keywords
Flow mediated dilation, Glucose control, Inflammation, Immune cell function, Cognition, Oxidative stress, Cardiovascular function
Brief summary
Post-prandial hyperglycemic excursions induce a cascade of deleterious effects on the body, including increased inflammation, production of reactive oxygen species, and impaired cardiovascular function. Ingestion of an exogenous oral ketone supplement blunts hyperglycemia in response to an oral glucose tolerance test. Accordingly, it is hypothesized that exogenous ketone supplement ingestion prior to a meal could be an effective strategy for blunting postprandial hyperglycemia. Therefore, the purpose of this study is to investigate the effect of short-term (14-days) pre-meal exogenous ketone supplementation on glucose control, cardiovascular function, inflammation, and oxidative stress in individuals at an elevated risk of type 2 diabetes.
Interventions
DIETARY_SUPPLEMENTExogenous ketone monoester
Participants will consume 20g of the oral ketone monoester supplement 15 minutes prior to each meal of the day for 14 days. All meals will be provided throughout the 14-day supplementation period.
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Elevated waist circumference (\>102 cm for males, \>88 cm for females) and/or Obesity (BMI \> 30 kg/m2) and/or Diagnoses of prediabetes based on A1C (5.7-6.4%) and/or fasting plasma glucose (5.6-6.9 mmol/l) using ADA criteria
Exclusion criteria
* Competitively trained endurance athlete * Actively attempting to lose weight * History of mental illness or existing neurological disease(s) * Previous cardiovascular events (i.e., heart attack, stroke) * Diagnoses of diabetes * Hypoglycemia * Irritable bowel syndrome or inflammatory bowel disease * Taking medication that may interfere with insulin sensitivity * Currently following a ketogenic diet or taking ketone supplements * Unable to commit for 2 separate 14-day trials and unable to follow a controlled diet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose control | 2 hours after a meal | Post-prandial glucose excursions will be measured by continuous glucose monitoring using the iPro2 CGM by Medtronic in both the active and placebo supplement conditions. Post-prandial glucose following breakfast, lunch, and dinner will be averaged together. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline histone acetylation at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Histone H3 acetylation status will be quantified by flow cytometry using conjugated acetyl-histone H3 antibody specific for Lys9 (Pacific Blue 445) and the conjugated acetyl-histone H3 antibody specific for Lys14 (Alexa Fluor 488). |
| Change from baseline mitochondrial superoxide production at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Oxidative Stress will be measured by mitochondrial superoxide production in blood lymphocytes, monocytes, and neutrophils by flow cytometry using the MitoSOX red assay (ThermoFisher #M36008) and total intracellular ROS via the DCFDA assay (Sigma #D6883) |
| Change from baseline cognition (executive functions) at 14 days | 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 iPad-based app BrainBaseline. The tests will be the Stroop test, task-switching test, digit-symbol substitution test, and the n-back test. |
| Change from baseline plasma glucose at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Venous blood samples will be taken and plasma glucose will be measured using a hexokinase method. |
| Change from baseline flow mediated dilation at 14 days | 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. |
| Change from baseline plasma free fatty acids at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Venous blood samples will be taken and free fatty acids will be measured by colorimetric assay. |
| Change from baseline interleukin-1(IL)-1beta at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Mature IL-1beta secretion will be quantified by ELISA run in duplicate |
| Change from baseline caspase-1 activation at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Caspase-1 activation will be quantified by flow cytometry. The fluorescent inhibitor probe FAM-YVAD-FMK binds covalently to activated caspase-1 and emits at 530nm |
| Change from baseline plasma insulin at 14 days | Day 0 (Pre-intervention) and Day 14 (post-intervention) | Venous blood samples will be taken and plasma insulin will be measured using a high-sensitivity human insulin ELISA. |
Countries
Canada
Outcome results
None listed