Type 2 diabetes mellitus (T2DM) Nutritional, Metabolic, Endocrine Type 2 diabetes mellitus
Conditions
Interventions
This trial is a 24-week randomised control trial with two arms. Randomisation (at the individual level, stratified by country) will occur once all baseline measures are completed and individuals are c
Sponsors
University of Leicester
McGill University Health Centre
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 24/08/2022: 1. Age 18 to 45 years, inclusive 2. Type 2 diabetes: physician diagnosis more than 3 months and less than 6 years previously 3. Hemoglobin A1c 6.5% to 10%, inclusive if not taking glucose-lowering medication; 6.0% to 10% if taking glucose-lowering medication 4. Body mass index 30 kg/m² to 45 kg/m², inclusive if White or Indigenous¹, 27 kg/m² to 45 kg/m², inclusive if other background, including mixed 5. Weight stability: weight changes of less than 5 kg over the prior 6 months 6. Walking ability: able to walk without assists and to participate in structured exercise training requiring the lower limbs 7. Capacity: able to understand written and spoken English and/or French 8. Able to provide informed consent 9. Willing to be randomized and able to participate 10. Willing to attend supervised exercise sessions, if so randomized 11. Willing to adopt low energy diet, including abstinence from alcohol, if so randomized 12. Willing to self-monitor glucose and blood pressure at the required frequency, if randomized to the low energy diet plus supervised exercise arm ¹Term for the original peoples of North America and their descendants; includes First Nations, Inuit, and Métis peoples ²An exception is made for women who are on insulin therapy in case of pregnancy occurrence because of insulin’s established safety profile in pregnancy, rather than because of inability to control glycemia on oral agents alone. If these women are willing and able to use a reliable form of contraception, they may be enrolled. Previous inclusion criteria: 1. Age 18 to 40 years, inclusive 2. A clinically coded diagnosis of T2DM between 3 months and 6 years previously 3. HbA1c 6.5% (48 mmol/mol) to 10% (86 mmol/mol), inclusive, within the last 12 months 4. BMI =30 kg/m² and =45 kg/m² (= 27.0 kg/m² if BAME (self-identified)), within the last 12 months 5. Self-reported stable weight over the previous 6 months (<+/- 5 kg) 6. Treatment stable; no significant change to glucose-lowering regimen in the preceding 3 months, as determined by a study investigator 7. Able to provide informed consent 8. Able to understand written and spoken English 9. Able to take part in structured exercise training requiring the lower limbs (e.g., able to walk without assists or impairment)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 24/08/2022: 1. Other diabetes types: 1.1. Type 1 diabetes 1.2. Gestational diabetes 1.3. Monogenic diabetes 2. Poorly controlled blood pressure: resting systolic blood pressure greater than 150 mmHg or resting diastolic blood pressure greater than 90 mmHg diastolic 3. Weight loss interventions: currently participating in a weight reduction program in addition to routine care 4. Previous bariatric surgery 5. Medications: 5.1. Insulin therapy² 5.2. Use of licensed weight loss medications 5.3. Significant changes in glucose-lowering medications in the prior 3 months, as judged by study physicians 5.4. Steroids by mouth or injection 6. Allergies: self-reported allergies or intolerances to components of the meal replacement products (e.g., milk protein allergy) 7. Dietary practices that prohibit the use of meal replacement products 8. Pregnancy, lactation or planning to become pregnant in the next 8 months 9. Eating disorder: self-reported or diagnosed 10. Substance abuse: alcohol, drugs 11. Estimated glomerular filtration rate: less than 60 ml.min-1 per 1.73m² 12. Retinopathy: receiving or requiring active treatment for retinopathy 13. Clinically manifest vascular disease: 13.1. Myocardial infarction 13.2. Stroke 13.3. Peripheral vascular disease 14. Other cardiac disease: 14.1. Heart failure 14.2. Atrial fibrillation 14.3. Pacemaker 14.4. Implantable cardioverter defibrillator (ICD) 15. Other conditions that could impact weight and/or safety: active malignancy or other chronic disease 16. Run-in phase: 16.1. Failure to complete at least 5 or requested 7 days of accelerometer wear 16.2. Failure to complete a food diary for three weekdays and one weekend day Previous exclusion criteria: 1. Individuals with type 1, gestational or monogenic diabetes mellitus 2. On insulin therapy (An exception may be made for women who are on insulin therapy in case of pregnancy occurrence because of insulin’s established safety profile in pregnancy, rather than because of inability to control glycaemia on oral agents alone. If these women are willing and able to use a reliable form of contraception, they may be enrolled.) 3. eGFR 150 mmHg systolic and/or >90 mmHg diastolic. In the case of borderline hypertension, individuals will be offered the opportun
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 26/08/2022: Diabetes remission measured through HbA1c collected by venous blood sampling at Week 24. HbA1c below 6.5% without glucose-lowering medication during the prior 12 weeks will be defined as remission. Previous primary outcome measures: Diabetes remission defined as HbA1c <6.5% (48 mmol/mol) without prescribed glucose-lowering medications between 12 and 24 weeks of the study period. HbA1c will be obtained through a venous blood sample. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 26/08/2022: Measured at baseline, week 12 and week 24 unless specified otherwise: 1. Other remission, glycemic, and insulin resistance measures: 1.1. Diabetes remission measured through venous blood sampling at Week 12 1.2. Fasting glucose and insulin, Homeostatic Model Assessment for Insulin Resistance measured through venous blood sampling 2. Main cardiovascular magnetic resonance imaging (CMR) measures: 2.1. Left ventricular peak early diastolic strain rate (circumferential and longitudinal) measured through an MRI scan at Baseline and Week 24 only 2.2. End-diastolic mass to volume ratio measured through MRI scan at Baseline and Week 24 only 3. Main fitness measure: 3.1. VO2 peak measured through a graded treadmill exercise test 4. Main fat and lean mass measures: 4.1. Total fat and lean soft tissue mass measured by dual-energy X-ray absorptiometry (DXA) scan 4.2. Weight (measured on scales) and body mass index (BMI) 5. Cardiometabolic indicators: 5.1. Hypertension remission, systolic and diastolic blood pressure, heart rate measured using a standardised blood pressure cuff procedure 5.2. Total cholesterol, HDL, LDL, and triglycerides measured through venous blood sampling. Other secondary outcomes: 6. Renal function measures: 6.1. Creatinine and estimated glomerular filtration rate measured through venous blood sampling 6.2. Urine albumin to creatinine ratio measured through urine sampling 7. Hepatic function measures: 7.1. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and bilirubin measured through venous blood sampling 8. Depression, anxiety, and distress measured using the Hospital Anxiety and Depression Scale and Diabetes Distress Scale 9. Indirect calorimetry: 9.1. Resting metabolic rate measured through indirect calorimetry (ventilated hood system) 10. Additional cardiac and aortic MRI-based measures: 10.1. Longitudinal and circumferential measures of systolic strain, end-syst | — |
Countries
Canada, England, United Kingdom
Contacts
Public ContactMatthew;Debbie McCarthy;Chan
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Outcome results
None listed