Mechanisms of Insulin Resistance and Exercise in South Asians
Primary Purpose
Insulin Resistance
Status
Suspended
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Aerobic exercise programme
Resistance exercise programme
Sponsored by
About this trial
This is an interventional prevention trial for Insulin Resistance focused on measuring insulin resistance, aerobic exercise, resistance exercise, exercise training, South Asians
Eligibility 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
Sites / Locations
- University of Glasgow
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Experimental
Arm Label
Control Group
Aerobic exercise group
Resistance exercise group
Arm Description
Participants assigned to the control arm of the study will be asked to maintain their normal dietary and exercise habits.
Participants randomised to the aerobic exercise intervention will undertake a 12-week aerobic exercise training programme.
Participants randomised to the resistance exercise intervention will undertake a 12-week aerobic exercise training programme.
Outcomes
Primary Outcome Measures
Whole-body Insulin sensitivity
Change in whole-body insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp.
Secondary Outcome Measures
Insulin-stimulated GLUT4 translocation
Change in insulin-stimulated GLUT4 translocation in muscle biopsies from vastus lateralis using immunofluorescence microscopy
Microvascular blood volume
Change in fold-increase in insulin stimulated quadriceps muscle blood volume measured using contrast enhanced ultrasound.
Muscle mitochondrial function
Change in mitochondrial function (oxygen consumption rate) in isolated skeletal muscle mitochondria from the vastus lateralis measured using respirometry
Lipid droplet content in skeletal muscle
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
Lipid droplet proximity to mitochondria in skeletal muscle
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
Microvascular density in skeletal muscle
Change in fibre-type specific capillarisation in muscle biopsies from vastus lateralis
Change in enzymes controlling insulin-mediated increases in perfusion in skeletal muscle
Change in endothelial specific protein content and phosphorylation of key microvascular enzymes in muscle biopsies from vastus lateralis assessed using quantitative immunofluorescence.
Maximal oxygen uptake
Change in maximal oxygen uptake consumption assessed using continuous incremental uphill walking protocol until volitional exhaustion.
Muscle maximal voluntary contraction
Change in knee extensor muscles maximal voluntary contraction
Lower body muscle strength
Change in 1-RM (one maximal repetition) (kg) for leg press.
Upper body muscle strength
Change in 1-RM (one maximal repetition) (kg) for chest press.
Grip strength
Change in grip strength (kg).
Fat mass
Change in fat mass measured with bioelectrical impedance analysis (BIA).
Fat-free mass
Change in fat-free mass measured with bioelectrical impedance analysis (BIA).
Weight
Change in weight (kg).
Waist circumference
Change in waist circumference (cm)
Full Information
NCT ID
NCT04007926
First Posted
June 28, 2019
Last Updated
October 7, 2020
Sponsor
University of Glasgow
Collaborators
Medical Research Council
1. Study Identification
Unique Protocol Identification Number
NCT04007926
Brief Title
Mechanisms of Insulin Resistance and Exercise in South Asians
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Suspended
Why Stopped
COVID-19
Study Start Date
August 2021 (Anticipated)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Glasgow
Collaborators
Medical Research Council
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Resistance
Keywords
insulin resistance, aerobic exercise, resistance exercise, exercise training, South Asians
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomised controlled trial
Masking
None (Open Label)
Masking Description
Masking is not possible due to nature of intervention (exercise training programme).
Allocation
Randomized
Enrollment
66 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
Participants assigned to the control arm of the study will be asked to maintain their normal dietary and exercise habits.
Arm Title
Aerobic exercise group
Arm Type
Experimental
Arm Description
Participants randomised to the aerobic exercise intervention will undertake a 12-week aerobic exercise training programme.
Arm Title
Resistance exercise group
Arm Type
Experimental
Arm Description
Participants randomised to the resistance exercise intervention will undertake a 12-week aerobic exercise training programme.
Intervention Type
Behavioral
Intervention Name(s)
Aerobic exercise programme
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Resistance exercise programme
Intervention Description
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 Measure Information:
Title
Whole-body Insulin sensitivity
Description
Change in whole-body insulin sensitivity measured by hyperinsulinaemic-euglycaemic clamp.
Time Frame
Change between baseline and 12 weeks.
Secondary Outcome Measure Information:
Title
Insulin-stimulated GLUT4 translocation
Description
Change in insulin-stimulated GLUT4 translocation in muscle biopsies from vastus lateralis using immunofluorescence microscopy
Time Frame
Change between baseline and 12 weeks.
Title
Microvascular blood volume
Description
Change in fold-increase in insulin stimulated quadriceps muscle blood volume measured using contrast enhanced ultrasound.
Time Frame
Change between baseline and 12 weeks.
Title
Muscle mitochondrial function
Description
Change in mitochondrial function (oxygen consumption rate) in isolated skeletal muscle mitochondria from the vastus lateralis measured using respirometry
Time Frame
Change between baseline and 12 weeks.
Title
Lipid droplet content in skeletal muscle
Description
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
Time Frame
Change between baseline and 12 weeks.
Title
Lipid droplet proximity to mitochondria in skeletal muscle
Description
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
Time Frame
Change between baseline and 12 weeks.
Title
Microvascular density in skeletal muscle
Description
Change in fibre-type specific capillarisation in muscle biopsies from vastus lateralis
Time Frame
Change between baseline and 12 weeks.
Title
Change in enzymes controlling insulin-mediated increases in perfusion in skeletal muscle
Description
Change in endothelial specific protein content and phosphorylation of key microvascular enzymes in muscle biopsies from vastus lateralis assessed using quantitative immunofluorescence.
Time Frame
Change between baseline and 12 weeks.
Title
Maximal oxygen uptake
Description
Change in maximal oxygen uptake consumption assessed using continuous incremental uphill walking protocol until volitional exhaustion.
Time Frame
Change between baseline and 12 weeks.
Title
Muscle maximal voluntary contraction
Description
Change in knee extensor muscles maximal voluntary contraction
Time Frame
Change between baseline and 12 weeks.
Title
Lower body muscle strength
Description
Change in 1-RM (one maximal repetition) (kg) for leg press.
Time Frame
Change between baseline and 12 weeks.
Title
Upper body muscle strength
Description
Change in 1-RM (one maximal repetition) (kg) for chest press.
Time Frame
Change between baseline and 12 weeks.
Title
Grip strength
Description
Change in grip strength (kg).
Time Frame
Change between baseline and 12 weeks.
Title
Fat mass
Description
Change in fat mass measured with bioelectrical impedance analysis (BIA).
Time Frame
Change between baseline and 12 weeks.
Title
Fat-free mass
Description
Change in fat-free mass measured with bioelectrical impedance analysis (BIA).
Time Frame
Change between baseline and 12 weeks.
Title
Weight
Description
Change in weight (kg).
Time Frame
Change between baseline and 12 weeks.
Title
Waist circumference
Description
Change in waist circumference (cm)
Time Frame
Change between baseline and 12 weeks.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Gill, PhD
Organizational Affiliation
University of Glasgow
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Glasgow
City
Glasgow
ZIP/Postal Code
G12 8QQ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33159841
Citation
Marx N, Davies MJ, Grant PJ, Mathieu C, Petrie JR, Cosentino F, Buse JB. Guideline recommendations and the positioning of newer drugs in type 2 diabetes care. Lancet Diabetes Endocrinol. 2021 Jan;9(1):46-52. doi: 10.1016/S2213-8587(20)30343-0. Epub 2020 Nov 4. Erratum In: Lancet Diabetes Endocrinol. 2021 Jan;9(1):e1.
Results Reference
derived
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Mechanisms of Insulin Resistance and Exercise in South Asians
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