Pancreas lipotoxicity in type 2 diabetes: Edinburgh Diabetes Remission Study (EDRS)
| ISRCTN | ISRCTN36628439 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN36628439 |
| Sponsors | Accord (United Kingdom), NHS Lothian |
| Funder | Medical Research Council |
- Submission date
- 13/01/2026
- Registration date
- 19/01/2026
- Last edited
- 16/01/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
This study looks at how excess fat in the pancreas may cause type 2 diabetes and whether losing weight can reverse this process. Previous research shows that weight loss can lead to diabetes remission, but the reasons why are not fully understood. We aim to find out how the liver makes fat (de novo lipogenesis) and how fat moves in the blood, and how these affect the pancreas and insulin production. The study will compare four groups of participants (non-diabetic, pre-diabetic, short-duration type 2 diabetes, and long-duration type 2 diabetes) to understand the sequence of changes that lead to diabetes remission.
Who can participate?
Adults aged 45–79 years with a BMI between 30 and 45 kg/m². We will include four groups:
1. People without diabetes
2. People with pre-diabetes
3. People with type 2 diabetes for less than 6 years
4. People with type 2 diabetes for more than 10 years
Participants must be able to give informed consent, communicate in English, and be willing to follow the study diet and attend follow-up visits. Women must be post-menopausal.
What does the study involve?
All participants will follow a low-calorie diet (around 800 kcal per day) for 8–12 weeks, then receive support to maintain weight loss for up to 12 months. We will carry out blood tests, MRI scans of the pancreas and liver, and other assessments to understand changes in fat and metabolism. Some participants will also have a small fat biopsy.
What are the possible benefits and risks of participating?
Benefits may include weight loss and better blood sugar control, and in some cases remission of type 2 diabetes. Risks include hunger, changes in blood pressure or blood sugar when stopping medication, and discomfort during tests. Safety will be monitored throughout the study.
Where is the study run from?
Clinical Research Facility, Royal Infirmary of Edinburgh, Scotland (UK)
When is the study starting and how long is it expected to run for?
The study will start in January 2026 and is expected to run until December 2028.
Who is funding the study?
The study is funded by the Medical Research Council and sponsored by ACCORD (Academic and Clinical Central Office for Research and Development) (UK)
Who is the main contact?
Study Team, edrs@ed.ac.uk
Contact information
Public
University of Edinburgh
Centre for Cardiovascular Science
Institute for Neuroscience & Cardiovascular Research
Edinburgh BioQuarter
47 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
| Phone | +44 (0)1312426717 |
|---|---|
| edrs@ed.ac.uk |
Scientific, Principal investigator
University of Edinburgh
Centre for Cardiovascular Science
Institute for Neuroscience & Cardiovascular Research
Edinburgh BioQuarter
47 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
| Phone | +44 (0)131 2426691 |
|---|---|
| Ahmad.Al-Mrabeh@ed.ac.uk |
Study information
| Primary study design | Interventional | |
|---|---|---|
| Allocation | Non-randomized controlled trial | |
| Masking | Open (masking not used) | |
| Control | Uncontrolled | |
| Assignment | Parallel | |
| Purpose | Treatment | |
| Scientific title | Mechanisms mediating reversible lipotoxicity of the pancreas in obesity-induced type 2 diabetes: Edinburgh Diabetes Remission Study (EDRS) | |
| Study acronym | EDRS | |
| Study objectives | To investigate how excess fat accumulation in the pancreas contributes to the pathophysiology of type 2 diabetes and how structured weight loss can reverse this process. The study will compare metabolic responses across four groups: non-diabetic, pre-diabetic, short-duration T2D (<6 years), and long-duration T2D (>10 years). Specifically, the study aims to: 1. Quantify hepatic de novo lipogenesis (DNL) and lipoprotein metabolism before and after weight loss. 2. Assess changes in intrapancreatic fat, beta-cell function, and pancreas morphology. 3. Determine whether changes in DNL and intra-organ fat are associated with diabetes remission. | |
| Ethics approval(s) |
Approved 03/07/2025, North West – Greater Manchester West Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; gmwest.rec@hra.nhs.uk), ref: 23/NW/0368 | |
| Health condition(s) or problem(s) studied | Type 2 diabetes | |
| Intervention | All participants will follow a Total Diet Replacement (TDR) program providing ~800 kcal/day using commercially available soups and shakes for 8–12 weeks, followed by a 2-week food reintroduction phase and structured weight maintenance support for up to 6–12 months, supervised by a research dietitian. The intervention includes dietary counseling, monitoring, and metabolic assessments (blood tests, MRI scans, mixed meal tests, and adipose tissue biopsies in a subgroup). | |
| Intervention type | Behavioural | |
| Primary outcome measure(s) |
| |
| Key secondary outcome measure(s) |
| |
| Completion date | 31/12/2028 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 45 Years |
| Upper age limit | 79 Years |
| Sex | All |
| Target sample size at registration | 104 |
| Key inclusion criteria | 1. Obese (BMI: 30-45 kg/m²) who have had T2D for less than 6 years or longer than 10 years, and are on treatment with diet alone or diet plus oral medication 2. Obese (BMI: 30-45 kg/m²) who are at the pre-diabetes stage, defined as fasting blood glucose 5.6-6.9 mmol/L 3. Obese (BMI: 30-45 kg/m²) who are non-diabetic (control group) 4. Age between 45 and 79 years inclusive 5. Men and women, however, post-menopausal women only (to exclude sex hormone effects on lipid metabolism) 6. Good communication in English (able to give informed consent and follow dietary advice) 7. Willing and able to adhere to the study protocol, including dietary intervention and scheduled follow-up visits |
| Key exclusion criteria | 1. Insulin therapy 2. HbA1c >12% (108 mmol/mol) 3. Weight loss >5 kg in the last 6 months 4. Recent MI (within 6 months) 5. Known cancer in the last 5 years 6. First-degree relatives of people with T2D (control group) 7. History of gestational diabetes 8. MRI contraindications (metal implants, claustrophobia) 9. Alcohol >14 units/week 10. Advanced kidney or liver disease 11. Use of steroids or antipsychotics 12. Participation in another clinical trial 13. Life expectancy <1 year 14. Allergy to local anaesthetic (for biopsy subgroup) 15. Any disorder that may jeopardise safety or compliance |
| Date of first enrolment | 12/01/2026 |
| Date of final enrolment | 01/06/2028 |
Locations
Countries of recruitment
- United Kingdom
- Scotland
Study participating centre
Edinburgh
EH16 4SA
Scotland
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan |
Editorial Notes
14/01/2026: Study's existence confirmed by the North West - Greater Manchester West Research Ethics Committee.
