Does Estrogen Blunt the Effects of Exercise Training on Glycemic Control

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18-35
SponsorUniversity of Waterloo

About this trial

Previous research has found that males and females respond differently to exercise training, particularly with respect to improvements in blood sugar control and immune system health. This is crucial since insulin resistance, which can lead to type 2 diabetes and other health problems, affects millions of Canadians. People with insulin resistance often have higher inflammation. Exercise is known to improve insulin resistance and reduce inflammation, but females seem to benefit less from exercise compared to men. The investigators believe this difference might be due to estrogen, a hormone that helps regulate blood sugar (in non-exercising conditions) and reduce inflammation. Females have higher estrogen levels, which might explain their ability to regulate resting blood sugar control and also immune function at rest. Our research will investigate how estrogen influences the acute and chronic effects of exercise males. The investigators will study how estrogen influence's the body's response to exercise, particularly in terms of reducing inflammation and improving blood sugar levels as well as immune function. Overweight and obese males will undergo 2 weeks of high intensity interval training while taking either an estrogen supplement or placebo. Prior to and following training males will undergo an assessment of maximal fitness (VO2max test) and an oral glucose tolerance test. Prior to and following the acute exercise test blood samples will be taken to determine the acute effects of exercise on immune cell function and inflammation. Prior to and during the oral glucose tolerance test participants will have blood samples taken to determine glucose handling and insulin sensitivity. They will also have a muscle biopsy taken prior to and 1h into the oral glucose tolerance test to determine the effects of estrogen supplementation on insulin signaling, mitochondrial content and function, fat metabolism and fat storage in skeletal muscle.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Biological males (with no previous hormonal supplementation).

Between the ages of 18-35 years old

Non-smokers

Sedentary individuals (i.e., engaging in intentional moderate-to-vigorous physical activity <2x/week)

Disqualifiers

Any state that can impact the hormonal milieu (e.g., drug/hormonal supplementation related to health).

Usage of anti-inflammatory medications, >1 glucose lowering medications, insulin, platelet inhibitors, anti-coagulant medications or simvastatin, beta-blockers, weight loss medications (Orlistat, Saxenda, Contrave, Ozempic) or any medications known to affect protein metabolism (i.e., corticosteroids).

Presence of cardiovascular, respiratory, metabolic, autoimmune or renal disease.

Presence of any condition that makes the participant unable to participate in physical activity as determined using the CSEP Get Active Questionnaire.

Trial design

Design model

Parallel

Treatments tested in this trial

  • EXERCISE TRAINING WITH OR WITHOUT MEDICATION

    Other intervention

    2 weeks of high intensity interval training while either taking estrogen or placebo

Treatment groups

24 Participants
are divided into 2 treatment groups
Group A: EstrogenExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Glucose AUC

Glucose AUC determined from blood samples taken during a 2h oral glucose tolerance test

Time frame
Visit 3 (baseline) and Visit 11 (Day 16)

Secondary outcomes

1

Insulin resistance/sensitivity

at rest (HOMA-IR) and during a 2 h oral glucose tolerance test (Matsuda index)

Time frame
Visit 3 (baseline) and Visit 11 (Day 16)
2

Markers of insulin signaling

Western blot of the following markers: AMPKα Thr172 \& total AMPKα; phosphorylated Akt Ser437 \& total Akt; phosphorylated TBC1D4 Thr642 \& total TBC1D4; phosphorylated TBC1D1 Ser237 \& total TBC1D; total GLUT4 in human skeletal muscle in the fasted and insulin stimulated state

Time frame
Visit 3 (baseline) and Visit 11 (Day 16)
3

Membrane bound GLUT4

GLUT4 content at the membrane in the fasted and insulin stimulated state (determined via immunofluorescence)

Time frame
Visit 3 (baseline) and Visit 11 (Day 16)
4

Peripheral blood mononuclear cells

determination of immune cell response to acute exercise

Time frame
Visit 2 (baseline) and Visit 10 (Day 14)

Other outcomes

Sponsors and contacts

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