Polycystic ovary syndrome (PCOS) affects 1 in 5 females of reproductive age. Commonly characterized as a disorder of infertility, PCOS is often accompanied by 3 potent cardiovascular disease (CVD) risk factors: insulin resistance, endothelial dysfunction, and elevated blood pressure. Accordingly, PCOS is associated with the development of CVD, the second leading cause of death in females in Canada. However, effective treatments to improve cardiovascular health in PCOS are lacking. Exogenous ketone monoester (KME) ingestion has been shown to improves outcomes associated with insulin resistance, endothelial function, and blood pressure regulation in healthy individuals and individuals predisposed to CVD. Therefore, oral ketone supplements offer a practical and effective strategy for improving cardiovascular health; however, this treatment has yet to be evaluated in PCOS. Therefore, the overall goal of this project is to employ KME ingestion to improve markers of cardiovascular health in females with PCOS. On two different days, participants will consume either a beverage containing a ketone supplement or a beverage containing a placebo supplement. The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females with PCOS in comparison with female controls of similar age and body mass index. The effects of KME ingestion will be quantified on: 1) glycemic control during an oral glucose tolerance test; 2) endothelial function using the flow-mediated dilation test; 3) blood pressure and acute blood pressure regulation; and 4) hemodynamic responses to acute exercise.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
\- Ketone monoester supplement in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.45ml/kg body weight) ingested with water and vanilla-flavored stevia in a total volume of 100 ml.
100 ml water combined with 10ml bitter flavor and vanilla-flavored stevia
Cardiovascular Health and Autonomic Research Laboratory
Montreal, Quebec, Canada
RECRUITINGGlycemic responses to a 2-hr oral glucose tolerance test
\- Glucose is calculated by the area under the curve using the trapezoid method.
Time frame: 0-2.5 hours in the post-prandial period
Flow mediated dilation (FMD)
\- Endothelial function is assessed using the standard FMD; quantified as the percent increase in diameter from rest to peak diameter observed during reactive hyperemia (%FMD). The % change in diameter reflects the ability of the vessel to dilate in response to sheer stress induced by the flow following the release of occlusion. This reflects the function of the endothelium, or release of nitric oxide.
Time frame: 30 minutes
Systolic Blood Pressure (SBP)
\- SBP, measured in mmHg
Time frame: 2 hours
Diastolic Blood Pressure (DBP)
\- DBP, measured in mmHg
Time frame: 2 hours
Insulin area under the curve
\- Insulin area under the curve during oral glucose tolerance test
Time frame: 0-2.5 hours in the post-prandial period
C-peptide
\- C-peptide area under the curve during oral glucose tolerance test
Time frame: 0-2.5 hours in the post-prandial period
Glucagon-like peptide-1 (GLP-1)
\- GLP-1 area under the curve during oral glucose tolerance test.
Time frame: 0-2.5 hours in the post-prandial period
Glucose-dependent insulinotropic polypeptide (GIP)
\- GIP area under the curve during oral glucose tolerance test.
Time frame: 0-2.5 hours in the post-prandial period
Triglycerides
\- Triglycerides area under the curve during oral glucose tolerance test
Time frame: 0-2.5 hours in the post-prandial period
Insulinogenic index
\- (Insulin at 30 min - fasting insulin)/ (plasma glucose at 30 min- fasting plasma glucose).
Time frame: 0-2.5 hours in the post-prandial period
Arterial artery blood flow
\- Calculated as the product of mean blood flow velocity (cm/sec) and cross-sectional area (2Πr2) x 60 sec/min.
Time frame: 0-2.5 hours in the post-prandial period
Shear rate and low-flow mediated vasoconstriction to the FMD
\- Shear rate calculated as area under the curve from cuff deflation to the time of peak dilation using the trapezoidal rule, as well as low flow-mediated vasoconstriction during forearm occlusion, which provides an index of the endothelial contribution to resting vascular tone and which predicts cardiovascular disease risk.
Time frame: 30 minutes
Muscle sympathetic nerve activity (MSNA)
\- Measured using microneurography, and expressed in burst/min or bursts/100 heart beats
Time frame: 2 hours
Neurovascular transduction
\- Assessed by the MSNA signal (recorded in both raw and filtered/rectified/integrated formats for subsequent analyses) and arterial blood flow extracted on a beat-by-beat basis and processed using custom transduction software.
Time frame: 2 hours
Vascular resistance
\- Calculated as mean arterial pressure divided by Finometer-derived cardiac output
Time frame: 2 hours
Capillary blood Beta-OHB concentrations
\- Measures in mmol/L
Time frame: 0-2.5 hours in the post-prandial period
Serum testosterone
\- Measured in pg/ml.
Time frame: 5 minutes
Serum sex hormone binding globulin
\- Measured in pg/ml.
Time frame: 5 minutes
Serum estradiol
\- Measured in pg/ml.
Time frame: 5 minutes
Serum Progesterone
\- Measured in pg/ml.
Time frame: 5 minutes
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