Does Biological Sex Influence Insulin Sensitivity and Muscle Metabolism Following High-intensity Interval Exercise?

High-intensity interval exercise (HIIE) is a type of exercise that involves alternating periods of intense exercise with periods of rest. HIIE has been shown to improve many aspects of cardiovascular and metabolic health in a time-efficient manner (e.g., only 20 minutes per exercise session). An important health benefit of exercise is improved blood sugar control, which can help reduce the risk of metabolic diseases like type 2 diabetes. A single session of HIIE has been shown to improve blood sugar in males, but it is unknown if females achieve the same health benefit. It is also not fully understood how exercise improves blood sugar in males and females. Therefore, the purpose of this project is 1) to determine if a single session of HIIE improves blood sugar control in males and females, and 2) to evaluate if changes in skeletal muscle can explain the beneficial effects of HIIE on blood sugar.

Study Overview

• Status: Completed
• Conditions: Exercise
• Intervention / Treatment: Other: Seated Rest (Non-exercise control); Other: High-intensity interval exercise

Detailed Description

The primary purpose of this study is to determine if biological sex influences the effects of high-intensity interval exercise (HIIE) on insulin sensitivity and muscle mechanisms. The investigators will measure insulin sensitivity and muscle outcomes of participants on two separate occasions: 1) Following 30 minutes of sitting in the lab; and 2) Following a single session of HIIE on a stationary bike. Insulin sensitivity will be measured by taking blood samples after participants consume a sugary drink. Muscle outcomes will be measured by taking a small amount of muscle from the vastus lateralis (thigh) muscle. Groups of male and female participants will be recruited and tested using best practice guidelines for sex-based comparisons of exercise responses.

The study will advance knowledge regarding the potential for biological sex to influence the metabolic responses high-intensity exercise.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S2C9
      • Goldring Centre for High Performance Sport

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-35 yrs
• VO2peak considered recreationally active as defined as 'fair' or 'good' (males: 41.6- 50.5ml/kg/min; females: 35-41.9 ml/kg/min) based on Canadian Society for Exercise Physiology (CSEP) normative fitness values.
• BMI between 18-27 kg/m2
• 1-3 structured exercise sessions/week, and not training for any specific sport
• Weight stable (within ± 2kg for at least 6 months)
• Eumenorrheic (female only), defined as menstrual cycle lengths ≥ 21 days and ≤ 35 days resulting in 9 or more consecutive periods per year)
• Non-smoker

Exclusion Criteria:

• Diagnosed with cardiovascular or metabolic disease, hyper- or hypogonadism, and/or polycystic ovarian syndrome (PCOS)
• The use of medication for managing blood glucose or lipid metabolism
• Current use of oral contraceptives or use within the last 3 months
• Irregular menstrual cycles (<21 days or >35 days)
• Pregnant, lactating, or menopausal
• Recreational smoking of any kind
• Inability to perform the study exercise protocols or follow the pre-trial dietary or physical activity controls
• Taking medications affecting substrate metabolism (corticosteroids or nSAIDs)
• Actively engaging in a low-carbohydrate diet (e.g., ketogenic, Atkins)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Females; Female participant group	Other: Seated Rest (Non-exercise control); Sitting for 30 minutes; Other: High-intensity interval exercise; Performing a single session of high-intensity interval exercise on a cycle ergometer
Experimental: Males; Male participant group	Other: Seated Rest (Non-exercise control); Sitting for 30 minutes; Other: High-intensity interval exercise; Performing a single session of high-intensity interval exercise on a cycle ergometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin area under the curve	Insulin area under the curve measured during glucose tolerance test	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose area under the curve	Glucose area under the curve measured during glucose tolerance test	3 hours
Mean insulin concentration	Mean insulin concentration measured during glucose tolerance test	3 hours
Mean glucose concentration	Mean glucose concentration measured during glucose tolerance test	3 hours
Peak insulin concentration	Peak insulin concentration measured during the glucose tolerance test	3 hours
Peak glucose concentration	Peak insulin concentration measured during the glucose tolerance test	3 hours
Insulin:glucose ratio	Insulin to glucose ration measured during the glucose tolerance test	3 hours
Postprandial glucose oxidation	Postprandial glucose oxidation measured with a metabolic tracer	3 hours
Skeletal muscle glycogen content	Muscle glycogen use during exercise	immediately before and after exercise
Skeletal muscle contractile signaling protein content	Measured via western blotting	immediately before and after exercise
Skeletal muscle insulin signaling	Measured via western blotting	1hr into glucose tolerance test
Mitochondrial gene expression	Measured via Reverse transcription polymerase chain reaction	Change from pre-exercise to 3hr post-exercise
Muscle protein synthesis rates	Muscle protein synthesis rates assessed by incorporation of oral stable isotope tracer following exercise	3hr post-exercise
Local muscle oxygenation	Muscle oxygenation (vastus lateralis) assessed with near-infrared spectroscopy (NIRS)	During exercise
Local muscle oxygenation	Muscle oxygenation (vastus lateralis) assessed with NIRS during and following thigh cuff inflation	Pre-exercise, immediately post-exercise and 2 hrs post-exercise

Collaborators and Investigators

• Sponsor: University of Toronto
• Investigators: Study Director: Stephanie Estafanos, MSc, University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2023
• Primary Completion (Actual): June 26, 2025
• Study Completion (Actual): June 26, 2025

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: October 4, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 44435

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
• product manufactured in and exported from the U.S.: No