Muscle in Obesity: Imaging, Function and microRNA

Study Overview
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Brief Summary
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Growing evidence suggests that dynapenic abdominal obesity is associated with a greater risk of falls, functional disability and hospitalisation compared to those with dynapenia, obesity or neither phenotype. Understanding the pathogenesis underlying this phenotype has the potential to inform potential treatment strategies. MicroRNAs can act as messengers at the cellular level to promote or block processes for muscle growth and repair, amongst other things. There is evidence that ageing changes microRNA levels in the muscle and that these changes may result in reduced muscle quality and quantity. However, it is not known whether being obese can change microRNA levels in muscle and how this relates to physical performance. The aim of this study is to investigate the effect of dynapenic abdominal obesity on microRNA levels in serum and muscle quality and quantity in the legs of older women. This is an observational, cross-sectional study. The investigators will recruit 4 groups of older women: normal weight, normal weight with dynapenia, obese and obese with dynapenia. The investigators will measure the microRNA levels in serum. The investigators will measure the quantity and fat content of muscle in the legs using magnetic resonance imaging. Muscle strength, fatigue and balance will be measured using gait (walking) analysis, balance tests, and a machine designed to measure leg strength and fatigue. The investigators will measure and compare microRNA levels between groups. The investigators will use databases and computer programmes to look at all of the microRNAs which are different between groups and see how they affect the muscle. The investigators will compare muscle strength, size and fatigue between groups. The investigators will explore relationships of muscle quantity and quality measures with microRNA changes in the muscle. This approach will allow the investigators to understand how obesity affects the microRNA profile of muscle and whether this translates into impairment of function and mobility.

Official Title
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Muscle in Obesity: Imaging, Function and microRNA

Conditions
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Muscle Function

Intervention / Treatment
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* Other: observational study


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Caucasian Female BMI 18.5-25 or 30-40kg/m2 Ages 60-80 years Sufficiently mobile to undergo scanning and biomechanical testing Able to remain motionless during scans Able and willing to participate in the study and provide written informed consent Exclusion Criteria: BMI 18.5-25kg/m2 AND waist circumference >88cm i.e. normal weight AND abdominally obese BMI 30-40kg/m2 AND waist circumference <88cm i.e. obese AND not abdominally obese History of any long-term immobilisation (duration greater than 2 weeks in the past 12 months) History of hospital admission in the past 3 months History of recent significant weight loss (5% in 3 months or 10% in 6 months) Diabetes mellitus History of current conditions which may affect muscle metabolism Malabsorption syndromes e.g. inflammatory bowel disease, pancreatic insufficiency etc. Chronic renal disease Diagnosed eating disorder Conditions which prevent the undertaking or analysis of the MRI and DXA scans or the interpretation of their results e.g. hip prosthesis, metal implants etc. Conditions which prevent the undertaking of the fatigue protocols e.g. hypertension etc. Use of medications or treatment known to affect muscle metabolism o Anabolic steroids, glucocorticoids, antiretrovirals etc. Excessive alcohol intake defined as greater than 21 units per week Competitive athlete, defined as participating in competitive sport at amateur or professional level Conditions which prevent the undertaking of a 6-minute walking test e.g. unstable angina or myocardial infarction during the previous month.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| normal weight, not dynapenic<br>BMI 18.5 to 25kg/m2, waist circumference <= 88cm, healthy women aged 60-80 years, time to complete 5 chair stands <15 seconds | Other: observational study<br>* observational study<br>|
| normal weight, dynapenic<br>BMI 18.5 to 25kg/m2, waist circumference <= 88cm,healthy women aged 60-80 years, time to complete 5 chair stands >15 seconds | Other: observational study<br>* observational study<br>|
| obese, not dynapenic<br>BMI 30 to 40kg/m2, waist circumference > 88cm, healthy women aged 60-80 years, time to complete 5 chair stands <15 seconds | Other: observational study<br>* observational study<br>|
| obese, dynapenic<br>BMI 30 to 40kg/m2, waist circumference > 88cm, women aged 60-80 years, time to complete 5 chair stands >15 seconds | Other: observational study<br>* observational study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differential microRNA expression, expressed as fold-change and p-values, measured using real time quantitative polymerase chain reaction (RT-qPCR) between normal weight and obese groups, further stratified by dynapenia | Serum analyses | 1 day (one measurement ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean difference in distance walked during 6 minute walk test between normal weight and obese, further stratified by dynapenia | 6 Minute walk test | 1 day (one measurement ) | 
| mean difference in muscle mass and volume measures between normal weight and obese, further stratified by dynapenia MRI | MRI (Magnetic Resonance Imaging) | 1 day (one measurement ) | 
| mean difference in muscle mass and volume measures between normal weight and obese, further stratified by dynapenia DXA | DXA (dual energy X-ray absorptiometry) | 1 day (one measurement ) | 
| mean difference in muscle strength between normal weight and obese, further stratified by dynapenia | Isokinetic dynamometer | 1 day (one measurement ) | 
| mean difference in fatigue between normal weight and obese, further stratified by dynapenia | kinetic change in gait parameters from Opal accelerometers | 1 day (one measurement ) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, sarcopenia, dynapenia, microRNA