Study Results
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Basic Information
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ACTIVE_NOT_RECRUITING
NA
30 participants
INTERVENTIONAL
2018-02-01
2028-01-31
Brief Summary
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In order to examine whether Rab3 is an early biomarker of insulin resistance, we aim to measure the levels of this protein and its interactors in fat and muscle samples from insulin resistant individuals. It has been shown that insulin sensitivity can be improved with an intervention as short as three weeks when net energy intake is sufficiently reduced. Therefore, by taking the same measurements before and after this three week intervention we can observe any improvements in Rab3 expression and insulin sensitivity at a cellular level.
There is also evidence for an effect of the gut microbiome on insulin sensitivity so we will measure any changes that take place in the gut microbiome following this intervention, which can be determined from faecal samples taken before and after the three weeks.
Detailed Description
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We hypothesise that this downregulation of Rab3 is associated with the development of insulin resistance and its activity would increase following the restoration of insulin sensitivity. The primary aim of this study is to examine the effect on Rab3 levels and GLUT4 trafficking of a diet and exercise intervention that has been previously shown to increase insulin sensitivity. Additionally, the gut microbiome will be studied before and after the intervention to determine any relationship to insulin sensitivity. Recent evidence suggests the microbiome has a significant role in the development of insulin resistance through a number of potential mechanisms. Infusion of microbiota from lean donors has been shown to result in improved insulin sensitivity in male recipients with metabolic syndrome, with concomitant increases in the prevalence of butyrate-producing intestinal microbiota. Exercise is associated with greater microbial diversity, including increases in butyrate-producing microbes. No study to date has monitored insulin sensitivity and microbiota composition before and after an exercise and diet intervention, and so this will lead to a better understanding of the mechanisms that lead to insulin resistance and subsequently type 2 diabetes.
The study participants will include males and females aged between 40-65 years who fit the criteria for inclusion. After monitoring of normal daily activities for 7 days, volunteers will reduce their calorie intake by 5000 kcal/week and take part in 5 weekly exercise sessions for 3 weeks. Participants will attend one session of laboratory testing before and one after this period which will take place at the University of Bath. This intervention should be sufficient to improve insulin sensitivity and allow us to study the cellular changes that will have taken place during this time.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
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Intervention
Controlled diet and exercise.
The intervention will involve 3 weeks of a diet and exercise program designed to cause a net energy decrease of 7000 kcal/week compared to habitual behaviour. This will be achieved through:
* Five exercise sessions per week at 70% VO2 max, using 400 kcal per session.
* Reduction of their standard diet by 5000 kcal per week
Before and after this intervention period participants will take part in a trial day which includes measurement of body composition (using DEXA) and blood sugar control (oral glucose tolerance test). Samples of blood, adipose, skeletal muscle and faeces will also be taken.
Control
No interventions assigned to this group
Interventions
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Controlled diet and exercise.
The intervention will involve 3 weeks of a diet and exercise program designed to cause a net energy decrease of 7000 kcal/week compared to habitual behaviour. This will be achieved through:
* Five exercise sessions per week at 70% VO2 max, using 400 kcal per session.
* Reduction of their standard diet by 5000 kcal per week
Before and after this intervention period participants will take part in a trial day which includes measurement of body composition (using DEXA) and blood sugar control (oral glucose tolerance test). Samples of blood, adipose, skeletal muscle and faeces will also be taken.
Eligibility Criteria
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Inclusion Criteria
* Age 40-65
* BMI ≥25 to ≤ 40 kg/m2
* Physical activity level \<1.75 (daily average)
* Waist size \>80 cm (female) or \>94 cm (male)
* Weight stable for \>3 months
Exclusion Criteria
* Diagnosed diabetes
* Ongoing or planned lifestyle changes (diet/exercise)
* Recent large shift in bodyweight (\>2.5%) within the last 3 months?
* Smoker (or having ceased \<6mo ago)
* Metabolic disorders
* Hypertension defined as \>160/100
* Use of anti-inflammatory medication: NSAIDs
* Cardiovascular disease
* Any bleeding disorder or taking anticoagulant medication
* Use of antibiotics within the last three months
* Use of pro/pre-biotics within one month of first trial day.
40 Years
65 Years
ALL
Yes
Sponsors
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Teagasc
INDUSTRY
University of Bath
OTHER
Responsible Party
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Francoise Koumanov
Lecturer
Principal Investigators
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Francoise Koumanov, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Bath
Locations
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Department for Health, University of Bath
Bath, , United Kingdom
Countries
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References
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DiabetesUK, Facts and Stats. 2016: https://diabetes-resources-production.s3-eu-west-1.amazonaws.com/diabetes-storage/migration/pdf/DiabetesUK_Facts_Stats_Oct16.pdf.
Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000 Aug;106(4):473-81. doi: 10.1172/JCI10842. No abstract available.
Koumanov F, Pereira VJ, Richardson JD, Sargent SL, Fazakerley DJ, Holman GD. Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes. Diabetologia. 2015 Aug;58(8):1877-86. doi: 10.1007/s00125-015-3627-3. Epub 2015 May 30.
Walhin JP, Dixon NC, Betts JA, Thompson D. The impact of exercise intensity on whole body and adipose tissue metabolism during energy restriction in sedentary overweight men and postmenopausal women. Physiol Rep. 2016 Dec;4(24):e13026. doi: 10.14814/phy2.13026.
Utzschneider KM, Kratz M, Damman CJ, Hullar M. Mechanisms Linking the Gut Microbiome and Glucose Metabolism. J Clin Endocrinol Metab. 2016 Apr;101(4):1445-54. doi: 10.1210/jc.2015-4251. Epub 2016 Mar 3.
Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012 Oct;143(4):913-6.e7. doi: 10.1053/j.gastro.2012.06.031. Epub 2012 Jun 20.
Campbell SC, Wisniewski PJ 2nd. Exercise is a Novel Promoter of Intestinal Health and Microbial Diversity. Exerc Sport Sci Rev. 2017 Jan;45(1):41-47. doi: 10.1249/JES.0000000000000096.
Other Identifiers
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RC-FH1158
Identifier Type: -
Identifier Source: org_study_id