Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mechanisms of Insulin Resistance and Exercise in South Asians

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04007926
Recruitment Status : Suspended (COVID-19)
First Posted : July 5, 2019
Last Update Posted : October 8, 2020
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
Professor Jason Gill, University of Glasgow

Brief Summary:
This study determines the effect of aerobic and resistance exercise training on whole-body and skeletal muscle insulin sensitivity in south Asians and evaluate the mechanisms which contribute to improvements in insulin sensitivity after exercise training.

Condition or disease Intervention/treatment Phase
Insulin Resistance Behavioral: Aerobic exercise programme Behavioral: Resistance exercise programme Not Applicable

Detailed Description:
South Asians (SA) have 2-4 fold higher risk of type 2 diabetes and develop the disease at lower body weights and younger ages than white Europeans. Lower cardiorespiratory fitness and capacity for muscle fat oxidation contributes substantially to SAs' greater insulin resistance, the extent to which this can be improved by exercise training is unclear. This randomised controlled trial will investigate the effects of a 12-week aerobic or resistance exercise training intervention on insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) in South Asian adults (22 control, 22 aerobic exercise group and 22 resistance exercise group). The study will also explore the mechanisms within skeletal muscle which mediate these changes by evaluating aerobic and resistance exercise-training induced changes: in basal and insulin-stimulated microvascular blood volume (using contrast-enhanced ultrasound); skeletal muscle mitochondrial function; and lipid droplet morphology and spatial interaction with mitochrondria, muscle fibre capillarisation, endothelial content of key enzymes controlling dilation/constriction and GLUT-4 translocation (using confocal immunofluorescence microscopy and transmission electron microscopy methods). Thus, this work will integrate physiological and molecular data to determine the extent to which exercise training can improve insulin sensitivity in SA and the mechanisms underpinning this improvement. This knowledge is important for optimising diabetes prevention interventions in SAs and identification of potential novel therapeutic targets.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised controlled trial
Masking: None (Open Label)
Masking Description: Masking is not possible due to nature of intervention (exercise training programme).
Primary Purpose: Prevention
Official Title: Effects of Exercise Training on Insulin Sensitivity in South Asians at Risk of Diabetes: the Roles of Skeletal Muscle Microvasculature and Mitochondrial Metabolism
Estimated Study Start Date : August 2021
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Control Group
Participants assigned to the control arm of the study will be asked to maintain their normal dietary and exercise habits.
Experimental: Aerobic exercise group
Participants randomised to the aerobic exercise intervention will undertake a 12-week aerobic exercise training programme.
Behavioral: Aerobic exercise programme
Participants will start with 3 x 20 minute exercise sessions in the first week, building up to 5 x 60 minutes of exercise by weeks 9-12 of the intervention, at an intensity of 65-80% of predicted maximum heart rate.

Experimental: Resistance exercise group
Participants randomised to the resistance exercise intervention will undertake a 12-week aerobic exercise training programme.
Behavioral: Resistance exercise programme
Participants will undertake two supervised sessions per week. The exercises performed during each session will consist of leg press, calf press, leg extension, leg curl, chest press, shoulder press, lateral pull down and seated row. Exercises will be performed at 60-80% 1RM. In weeks 1-2 participants will perform, during each session, a single set of 5-10 repetitions of each exercise (tiring but comfortably achievable) to ensure they are comfortable with the exercises and are performing these in the correct form. In weeks 3-4 participants will perform, during each session, two sets of each exercise to voluntary muscular failure - defined as not being able to perform single another repetition. In weeks 5-12 this will progress to 3 sets of each exercise to voluntary muscular failure, in each session.




Primary Outcome Measures :
  1. Whole-body Insulin sensitivity [ Time Frame: Change between baseline and 12 weeks. ]
    Change in whole-body insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp.


Secondary Outcome Measures :
  1. Insulin-stimulated GLUT4 translocation [ Time Frame: Change between baseline and 12 weeks. ]
    Change in insulin-stimulated GLUT4 translocation in muscle biopsies from vastus lateralis using immunofluorescence microscopy

  2. Microvascular blood volume [ Time Frame: Change between baseline and 12 weeks. ]
    Change in fold-increase in insulin stimulated quadriceps muscle blood volume measured using contrast enhanced ultrasound.

  3. Muscle mitochondrial function [ Time Frame: Change between baseline and 12 weeks. ]
    Change in mitochondrial function (oxygen consumption rate) in isolated skeletal muscle mitochondria from the vastus lateralis measured using respirometry

  4. Lipid droplet content in skeletal muscle [ Time Frame: Change between baseline and 12 weeks. ]
    Change in fibre type-specific (type 1 and type 2) and subcellular-specific (subsarcolemmal and intermyofibrillar) lipid droplet content in muscle biopsies from vastus lateralis using immunofluorescence microscopy

  5. Lipid droplet proximity to mitochondria in skeletal muscle [ Time Frame: Change between baseline and 12 weeks. ]
    Change in proportion of lipid droplets in contact with mitochondria in subsarcolemmal and intermyofibrillar compartments of type 1 and type 2 muscle fibres in muscle biopsies from vastus lateralis using immunofluorescence microscopy

  6. Microvascular density in skeletal muscle [ Time Frame: Change between baseline and 12 weeks. ]
    Change in fibre-type specific capillarisation in muscle biopsies from vastus lateralis

  7. Change in enzymes controlling insulin-mediated increases in perfusion in skeletal muscle [ Time Frame: Change between baseline and 12 weeks. ]
    Change in endothelial specific protein content and phosphorylation of key microvascular enzymes in muscle biopsies from vastus lateralis assessed using quantitative immunofluorescence.

  8. Maximal oxygen uptake [ Time Frame: Change between baseline and 12 weeks. ]
    Change in maximal oxygen uptake consumption assessed using continuous incremental uphill walking protocol until volitional exhaustion.

  9. Muscle maximal voluntary contraction [ Time Frame: Change between baseline and 12 weeks. ]
    Change in knee extensor muscles maximal voluntary contraction

  10. Lower body muscle strength [ Time Frame: Change between baseline and 12 weeks. ]
    Change in 1-RM (one maximal repetition) (kg) for leg press.

  11. Upper body muscle strength [ Time Frame: Change between baseline and 12 weeks. ]
    Change in 1-RM (one maximal repetition) (kg) for chest press.

  12. Grip strength [ Time Frame: Change between baseline and 12 weeks. ]
    Change in grip strength (kg).

  13. Fat mass [ Time Frame: Change between baseline and 12 weeks. ]
    Change in fat mass measured with bioelectrical impedance analysis (BIA).

  14. Fat-free mass [ Time Frame: Change between baseline and 12 weeks. ]
    Change in fat-free mass measured with bioelectrical impedance analysis (BIA).

  15. Weight [ Time Frame: Change between baseline and 12 weeks. ]
    Change in weight (kg).

  16. Waist circumference [ Time Frame: Change between baseline and 12 weeks. ]
    Change in waist circumference (cm)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male
  • South Asian ethnicity (self-report of both parents of Indian, Pakistani, Bangladeshi or Sri Lankan origin)
  • Age 30-65 years
  • At least 10% 10-year risk of developing type 2 diabetes, determined using the QDiabetes®2018 risk score (http://qdiabetes.org/2018/index.php)

Exclusion Criteria:

  • Female
  • Diabetes (physician diagnosed or HbA1c ≥48 mmol/mol on screening)
  • History of cardiovascular disease
  • Hypertension (taking anti-hypertensives or BP consistently ≥ 150/90 mmHg on screening).
  • Regular participation in vigorous physical activity
  • Regular participation in resistance exercise
  • Current smoking
  • Taking drugs or supplements thought to affect carbohydrate or lipid metabolism
  • Taking drugs affecting blood clotting (e.g. aspirin)
  • Current treatment with anti-obesity drugs
  • Any other significant illness that would prevent full participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04007926


Locations
Layout table for location information
United Kingdom
University of Glasgow
Glasgow, United Kingdom, G12 8QQ
Sponsors and Collaborators
University of Glasgow
Medical Research Council
Investigators
Layout table for investigator information
Principal Investigator: Jason Gill, PhD University of Glasgow
Layout table for additonal information
Responsible Party: Professor Jason Gill, Professor, University of Glasgow
ClinicalTrials.gov Identifier: NCT04007926    
Other Study ID Numbers: 265320
First Posted: July 5, 2019    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Professor Jason Gill, University of Glasgow:
insulin resistance
aerobic exercise
resistance exercise
exercise training
South Asians
Additional relevant MeSH terms:
Layout table for MeSH terms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases