Mechanisms of Insulin Resistance and Exercise in South Asians

NCT ID: NCT04007926

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: NA
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-31
• Study Completion Date: 2025-01-31

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.

Conditions

Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Control Group

Participants assigned to the control arm of the study will be asked to maintain their normal dietary and exercise habits.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Aerobic exercise group

Participants randomised to the aerobic exercise intervention will undertake a 12-week aerobic exercise training programme.

Group Type: EXPERIMENTAL

Aerobic exercise programme

Intervention Type: BEHAVIORAL

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.

Resistance exercise group

Participants randomised to the resistance exercise intervention will undertake a 12-week aerobic exercise training programme.

Group Type: EXPERIMENTAL

Resistance exercise programme

Intervention Type: BEHAVIORAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

University of Glasgow

OTHER

Sponsor Role: lead

Responsible Party

Professor Jason Gill

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason Gill, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Locations

University of Glasgow

Glasgow, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33159841 (View on PubMed)

Other Identifiers

265320

Identifier Type: -

Identifier Source: org_study_id