Reversing type 2 diabetes through a low calorie diet and supervised exercise
- Conditions
- Type 2 diabetes mellitus (T2DM)Nutritional, Metabolic, EndocrineType 2 diabetes mellitus
- Registration Number
- ISRCTN15487120
- Lead Sponsor
- niversity of Leicester
- Brief Summary
2022 Protocol article in https://pubmed.ncbi.nlm.nih.gov/36130753/ (added 22/09/2022)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 100
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)
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 <60 ml.min-1 per 1.73m²
4. Currently participating in a weight reduction program in addition to routine care
5. Previous bariatric surgery
6. Currently on injected steroids
7. Currently on weight loss medications (not including glucose-lowering medication)
8. Conditions that could impact weight (i.e., active malignancy/treatment in past year, pregnancy, lactation, planning to become pregnant in next 8 months)
9. Individuals with a self-reported or diagnosed eating disorder
10. Self-reported milk protein allergy or other allergy or dietary practice that prohibits the use of meal replacement products
11. Previous myocardial infarction, stroke, amputation secondary to T2DM/peripheral vascular disease, or other evidence of clinically manifest vascular disease
12. Previous clinically diagnosed atrial fibrillation
13. Previous clinically diagnosed heart failure
14. Pacemaker or implantable cardioverter-defibrillator (ICD)
15. Substance abuse. The requirement for alcohol abstinence during the initial 12 weeks will make it unlikely that individuals with alcohol dependence will enrol. Substance abuse will be queried.
16. Average resting blood pressure >150 mmHg systolic and/or >90 mmHg diastolic. In the case of borderline hypertension, individuals will be offered the opportun
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Current primary outcome measures as of 26/08/2022:<br>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.<br><br>Previous primary outcome measures:<br>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 Outcome Measures
Name Time Method