None listed
Conditions
Brief summary
This study aims to: 1. compare baseline phenotypes amongst those with recently identified prediabetes and type 2 diabetes, in Sydney, Australia and in Shanghai, China. 2. examine the effect of an exercise program on changes in metabolic end-points, complications, surrogate biomarkers, gut microbial profile and cognitive measures. 3. examine the effectiveness of an intervention to improve exercise maintenance. Study Hypotheses: 1. The phenotypes amongst those with recently identified prediabetes and type 2 diabetes, in Sydney, Australia and in Shanghai, China, differ in their body composition and adiposity (by DXA scan and abdominal MRI), and degree of insulin deficiency (by insulin, glucose and C-peptide measures). 2. A structured exercise program involving high intensity interval training (HIIT) and resistance exercise will lead to improved percentage of liver steatosis (1H-MRS), non-alcoholic fatty liver disease (steatosis greater than or equal to 5.5% and insulin-fibrosis measures), body composition, metabolic end-points (including HbA1c, fructosamine), lesser organ complications (including albuminuria, cardiac diastolic dysfunction, cardiac autonomic neuropathy, peripheral neuropathy), improved surrogate blood biomarkers of complications (including CD monocyte markers, CTGF and FAP), and more normal gut microbial profile, mood state and cognition. 3. An intervention aiming to improve exercise maintenance will result in improved exercise adherence, sustained outcomes in exercise parameters (adherence to exercise amount, greater intensity) and cardiovascular fitness, NAFLD, body composition, improved metabolic end-points, lesser organ complications, improved surrogate biomarkers of complications, and more normal gut microbial profile, mood state and cognitive function.
Interventions
540 individuals in total will be recruited. This cohort will be recruited in three glucose profile groups (newly diagnosed diabetic, pre-diabetic, normal glucose) of 180 individuals each, split evenly between Australian and Chinese sites such that 90 individuals of each glucose group is recruited in each country. Each glucose group in each country will be randomised in a 1:1 ratio between intervention and control. All participants randomised to the initial intervention treatment, and participant
540 individuals in total will be recruited. This cohort will be recruited in three glucose profile groups (newly diagnosed diabetic, pre-diabetic, normal glucose) of 180 individuals each, split evenly between Australian and Chinese sites such that 90 individuals of each glucose group is recruited in each country. Each glucose group in each country will be randomised in a 1:1 ratio between intervention and control. All participants randomised to the initial intervention treatment, and participants from the diabetic and pre-diabetic glucose groups from the initial control treatment will be followed up for the full duration of 2 years. Participants from the normal glucose group who are randomised to the initial control treatment will not be followed up after 12 weeks. Initial intervention: 3 exercise sessions per week, 2 sessions supervised in person by an Exercise Physiologist, consisting of High Intensity Interval Training (HIIT) at 85-95% Maximum Heart Rate (HRmax) for approximately 15 minutes including warm up and cool down, using a treadmill, cycle ergometer, or land based walking as appropriate, and Progressive Resistance Training (PRT) at 60-80% of 1 Repetition Maximum (1RM) using 8 resistance exercises of various major muscle groups, and 1 session of HIIT unsupervised per week, all for 12 weeks. The supervised sessions will be prescribed and delivered individually, either in an individual setting or in a group of up to three, as circumstances dictate. Compliance with this intervention will be measured by a record of sessions attended, which will be kept by trial staff, in conjunction with an exercise diary issued by the trial and kept by the participant for all unsupervised exercise sessions. After 12 weeks of the initial intervention/control treatment all participants who were randomised to the HIIT intervention will be re-randomised to either a follow up intervention (increased support group) or a follow up control treatment (text message support program group) and instructed to continue exercising independently. Follow-up intervention: An increased support group continuing until the 12 month follow up: Participants will be given a “Fitbit” physical activity monitoring device at week 12 of the exercise program and instructed to wear it every day. They will be taught how to use the Fitbit to ensure they reach 85-95% of their HR max for their HIIT sessions. Participants will be instructed to upload their data to an online database through which the researchers will track participants’ progress including heart rate data, estimated energy expenditure, body weight and exercise episodes. If participants are not meeting the targets for the HIIT exercise sessions they will be contacted using the escalating methods of email, text message or phone calls. The triggers for contact will be: 1. If a participant has not worn their Fitbit for two consecutive weeks an email will be sent. If there is no contact within a week, a text message will be sent. If there is still no contact within another week, the participant will be contacted by phone to discuss possible barriers to adherence and methods to enhance the process. 2. If the participant has worn the FitBit but has not achieved the prescribed HR for HIIT for at least one session per week, they will be sent an email after one week, a text message after two weeks, and called by phone after three weeks. 3. If a participant demonstrates compliance with their HIIT sessions, a positive feedback text message will be sent on a monthly basis to encourage them to continue. 4. If a participant demonstrates repeated non-compliance with the HIIT sessions, they will be invited to come back for a supervised session with the Exercise Physiologist to address any problems. Analysis of results will compare initial intervention groups against each other, maintenance intervention groups against each other, and Australian and Chinese cohorts against each other.
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- BMI greater than or equal to 25 kg/m2 (Non-Asian participants) or BMI greater than or equal to 23 kg/m2 (Asian participants) - Willing to undertake, and have no contraindications to, exercise testing and a program involving high intensity interval training program, resistance training or stretching - Willing to give written informed consent - Adequate understanding of national language - Access to either phone or internet (this is necessary when being contacted by the instructors throughout the duration of the trial) - Maximum weight of 140kg (equivalent MRI habitus limit) - No change in medication or dose for the previous three months - 90 participants at each site will be recruited from each of three glucose groups as defined by any one of the ADA criteria. That is Type 2 Diabetes Mellitus - HbA1c greater than or equal to 6.5%, Fasting Plasma Glucose (FPG) greater than or equal to 7.0 mmol/L, 2h post-Oral Glucose Tolerance Test Plasma Glucose (2hOGTT) greater than or equal to 11.1 mmol/L; Pre-diabetes - one occasion of any of the following in a participants medical history: HBA1c greater than or equal to 5.7% but less than 6.5%, FPG greater than or equal to 5.6 mmol/L but less than 7.0 mmol/L, 2hOGTT greater than or equal to 7.8 mmol/L but less than 11.1 mmol/L; Normal Glucose Profile - HbA1c less than 5.7%; FPG less than 5.6%; 2hOGTT less than 5.6 mmol/L.
Exclusion criteria
- Untreated dense insensate peripheral neuropathy that contraindicates exercise testing and training (as assessed by medical assessment) - Significant cardiovascular disease including current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease - Active foot ulcer - Musculoskeletal condition affecting ability to undertake exercise testing and training - Self-reported average weekly intake of alcohol >140g per week - Abnormalities noted by medical officer based on the resting ECG suggestive of unrecognised myocardial ischaemia: q waves, or ST wave depression. - Self-reported currently completing >75 min/week high intensity exercise or >150 min/week moderate intensity exercise. - Pregnancy, lactation or plans to become pregnant in the next 2 years. - Claustrophobia or ferrous metal implants/devices which contraindicate MRI scan. - Thiazolidinedione medication - History of Hepatitis B or C which has not been cured - Advanced chronic renal impairment (CKD state 4 or 5 or EFGR< 30) - Cirrhosis - Malignancy which is currently active or in remission for less than five years after last treatment (local basal and squamous cell skin cancer allowed) - Blood donation or transfusion within the past month - Haemoglobin concentration below local laboratory reference values (i.e. anaemia). - Alanine Transaminase (ALT) and/or Apartate Transaminase (AST) >3 times the Upper Limit of Normal (local laboratory reference values) - Any other condition deemed by the study physician that would prevent participation in the trial. - Weight change of greater than or equal to 5% in the past three months.
Outcome results
None listed