The Impact of 17beta-estradiol Treatment on Insulin Sensitivity, Immune Function, Inflammation and Skeletal Muscle Metabolism Following Exercise Training in Sedentary, Overweight Males
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Glucose AUC
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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)
- •Body mass index 27-32 kg/m2
- •Body fat % > 22%
排除标准
- •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.
- •Presence of injury that restricts exercise performance.
- •VO2max > 50th percentile for age.
- •Previous (within the last 2 months) or current use of ergogenic aids (i.e. creatine).
- •Previous or current use of weight loss medications, including liraglutide, semaglutide, orlistat, ozempic, etc.
- •History and/or diagnosis of blood clots or family history of blood clot disorders.
- •History of allergies or sensitivities to local anesthetic
- •Ophthalmic vascular disease
- •Classical migraines
- •History of thromboembolic disease
- •Consume 15 or more alcoholic drinks/week or 3 drinks per day
- •Bleeding disorders
- •Severe peripheral neuropathy
- •Muscular dystrophy
- •Prior bariatric surgery
- •Osteoporosis/osteopenia
- •Orthopaedic issues
- •Presence of GI disorders (i.e., Colitis, Crohns disease, Celiac disease)
- •Presence of liver disease or dysfunction (i.e., diagnosed NAFLD, NASH, cirrhosis, previous liver transplant)
- •History of cancer
- •Type 1 or 2 diabetes
- •Presence of renal disorders (creatinine > 140)
- •Uncontrolled hypertension (>140/90 mmHg)
- •History of allergies or sensitivities to estradiol or to any ingredient in the formulation or component of the container
- •History and/or diagnosis of blood clots or family history of blood clot disorders
- •Have an implantable electronic device
- •Medical psychiatric history of depression, bipolar, anxiety, suicidal ideation, etc.
- •Inherited clotting disorders
- •Chest pain or shortness of breath
- •Inflammatory disorders (e.g., inflammatory bowel disorder)
- •Significant weight loss in the 3-month period prior to the study (10% of total body weight)
- •Any kind of major surgery recently
- •Bleeding disorders
- •Active or history of thromboembolic disease (including confirmed venous thromboembolism)
- •Ophthalmic vascular disease
- •Classical migraines
结局指标
主要结局
Glucose AUC
时间窗: Visit 3 (baseline) and Visit 11 (Day 16)
Glucose AUC determined from blood samples taken during a 2h oral glucose tolerance test
次要结局
- Insulin resistance/sensitivity(Visit 3 (baseline) and Visit 11 (Day 16))
- Markers of insulin signaling(Visit 3 (baseline) and Visit 11 (Day 16))
- Membrane bound GLUT4(Visit 3 (baseline) and Visit 11 (Day 16))
- Peripheral blood mononuclear cells(Visit 2 (baseline) and Visit 10 (Day 14))
- Plasma cytokines from isolated PBMCs(Visit 2 (baseline) and Visit 10 (Day 14))
- Mitochondrial content(Visit 3 (baseline) and Visit 11 (Day 16))
- Mitochondrial respiration(Visit 3 (baseline) and Visit 11 (Day 16))
- intramyocellular lipid (IMCL) content(Visit 3 (baseline) and Visit 11 (Day 16))
- aerobic fitness (VO2max)(Visit 2 (baseline) and Visit 10 (Day 14))
- Sex hormone concentrations(Visit 3 (baseline) and Visit 11 (Day 16))
- Serum hormone concentrations(Visit 3 (baseline) and Visit 11 (Day 16))
- Sex hormone concentrations(Visit 3 (baseline) and Visit 11 (day 16))
- Serum hormone concentrations(Visit 2 (baseline) and visit 10 (day 14))
- Serum hormone concentrations(Visit 2 (baseline) and visit 10 (Day 14))
- Neurotransmitter concentration(Visit 2 (baseline) and Visit 10 (day 14))
研究者
Michaela Devries-Aboud
Associate Professor
University of Waterloo