The PRECISION-T2D Study: Precision Nutrition Study for Type 2 Diabetes

Study Overview
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Brief Summary
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Food plays a crucial role in determining blood glucose levels, especially in people with type 2 diabetes. Precision nutrition, which involves individually tailored dietary interventions, can be a powerful tool in managing blood glucose levels in people with type 2 diabetes. Previous studies found that changes in gut microbiota resulted from the dietary intervention, such as plant-based diet, might subsequently lead to different glycemic responses, and then different health outcomes. In this study, the investigators will characterize the blood glucose dynamics and gut microbiota of individuals with type 2 diabetes. They aim to assess the influence of plant-based diet on gut microbiota; they will also investigate the influence of gut microbiota on glycemic responses. Additionally, a series of individual N-of-1 trails will be integrated to compare the effects of a white bread breakfast and a whole wheat bread breakfast on glucose metabolism at the individual level.

Detailed Description
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Choice of design: The study is a two-arm intervention study integrated with N-of-1 design. Study population: Patients with type 2 diabetes. Screening Assessment: Prospective participants will be selected based on the pre-defined inclusion and exclusion criteria. Recruitment will be done over the phone and via the social media. Study duration: Each participant will take part in the study for a period of up to 1 month at baseline and have follow-up visits every 1-2 years. Dietary intervention: The PRECISION-T2D study will be divided into two subcohorts at baseline. Cohort 1 (n=1,200) will complete a home-based dietary intervention, while Cohort 2 (n=300) will complete a ward-based dietary intervention. In each cohort, participants will be randomly assigned to two groups: plant-based diet and conventional diabetic diet. Participants in the plant-based diet arm will be recommended to consume more fiber-rich foods, including whole grains, fruits, legumes and vegetables; to moderate their intake of fish, eggs and dairy products; and to avoid other animal products. Participants in the conventional diabetic diet arm will be recommended to have a diet following 2023 Chinese Diabetes Society guidelines. During the baseline visit (day one to day twelve), all participants (n=1,500) will be given standardized meals for breakfast. Participants who continue onto the home-based intervention will receive dietary recommendations on lunch and dinner meals, lasting up to one month following their clinical visit. Each participant will be provided with a list of recommended foods. Participants who continue onto the ward-based intervention will be given standardized meals for lunch and dinner. Participants will be asked to consume the entire amount of food indicated for the standardized meals and to record any leftover food. All participants will be asked to track their meals, snacks and drinks with instructions on how to record their daily dietary information. Participants will also be advised not to modify their exercise habits during the course of the study. During the participants' first baseline visit day, they will be asked to complete a baseline questionnaire to collect information on their lifestyle, dietary habits, history of medications, sleep quality and appetite. Anthropometric measurements, ultrasonography evaluation, and laboratory tests will be taken using standard protocols. Participants will then be asked to wear a continuous glucose monitor (CGM) for 14-day blood glucose monitoring, which will be done by a nurse. On day 14, participants will be asked to come in for a clinical visit where they will receive their CGM report and provide blood, saliva, urine and stool samples. On day 30, participants will be asked to come in for another clinical visit where they will undergo a liver MRI (Magnetic Resonance Imaging) scan and provide blood, saliva, urine and stool samples.

Official Title
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The PRECISION-T2D Study: Precision Nutrition Study for Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Other: White bread
* Other: Whole wheat bread
* Behavioral: Plant-based diet
* Other: Conventional diabetic diet
* Other: Follow-up visit every 1-2 years


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes; Living in Hangzhou for at least five years; Have the willingness or ability to complete the intervention and sample collection Exclusion Criteria: Mental and physical disability; Already is a vegetarian; Cancer and serious complications from type 2 diabetes, such as renal failure; Using insulin for more than 5 years; Unstable medical/medication status; Current alcohol or drug abuse; Taking antibiotics in the last three months

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plant-based diet<br>Participants in this arm will be recommended to consume more fiber-rich foods, including whole grains, fruits, legumes and vegetables; to moderate their intake of fish, eggs and dairy products; and to avoid other animal products. All participants are instructed not to modify their exercise habits during the intervention period. Additionally, if a participant is hospitalized during the intervention, a standardized plant-based diet will be provided. | Other: White bread<br>* After wearing CGM on Day 1, participants will be provided with white bread (76-77g) and milk (250mL) for breakfast on Day 3, Day 4, Day 7, Day 8, Day 10, Day 12.<br>* Other names: Breakfast A;Other: Whole wheat bread<br>* After wearing CGM on Day 1, participants will be provided with wheat bread (85-86g) and milk (250mL) for breakfast on Day 2, Day 5, Day 6, Day 9, Day 11, Day 13.<br>* Other names: Breakfast B;Behavioral: Plant-based diet<br>* After wearing CGM on Day 1, participants will be asked to follow the plant-based diet in next 30 days.<br>Other: Follow-up visit every 1-2 years<br>* Participants will be visited every 1-2 years. At each visit, face-to-face interviews, specimen collection, anthropometric measurements, ultrasonography evaluation, laboratory tests, and multi-omics data will be conducted.<br>|
| Experimental: Conventional diabetic diet<br>Participants in this arm will be recommended to have a diet following 2023 Chinese Diabetes Society guidelines. All participants are instructed not to modify their exercise habits during the intervention period. If a participant is hospitalized during the intervention, a standardized diabetic diet will be provided. | Other: White bread<br>* After wearing CGM on Day 1, participants will be provided with white bread (76-77g) and milk (250mL) for breakfast on Day 3, Day 4, Day 7, Day 8, Day 10, Day 12.<br>* Other names: Breakfast A;Other: Whole wheat bread<br>* After wearing CGM on Day 1, participants will be provided with wheat bread (85-86g) and milk (250mL) for breakfast on Day 2, Day 5, Day 6, Day 9, Day 11, Day 13.<br>* Other names: Breakfast B;Other: Conventional diabetic diet<br>* Volunteers will be asked to have a diet following 2023 Chinese Diabetes Society guidelines in next 30 days.<br>Other: Follow-up visit every 1-2 years<br>* Participants will be visited every 1-2 years. At each visit, face-to-face interviews, specimen collection, anthropometric measurements, ultrasonography evaluation, laboratory tests, and multi-omics data will be conducted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in gut microbiome profile | Shotgun metagenomic sequencing will be performed in stool samples. | Day 1 and Day 31 | 
| Blood glucose profile | Real-time blood glucose fluctuations will be recorded using continuous glucose monitoring. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid plaque | Grade carotid plaque using ultrasound. | At enrollment | 
| Carotid intima-media thickness | Measure of carotid intima-media thickness using ultrasound. | At enrollment | 
| Number of participants with chronic kidney disease | The serum creatine and urine creatine and protein will be measured and chronic kidney disease will be defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or and the presence of an elevated urine microalbumin/creatinine ratio. All cases will be verified by medical record review. | Up to 10 years | 
| Cognitive function | Cognitive function was measured by the Addenbrooke's Cognitive Examination-Revised (ACE-R). The original 26 components were combined to produce five subscores, 100 in total. The cutoff for dementia is 82-88/100. | Up to 10 years | 
| Changes in fasting blood glucose | Fasting glucose will be examined in mmol/L. | Day 1 and Day 31 | 
| Changes in fasting blood C-peptide | Fasting blood C-peptide will be examined in μg/L. | Day 1 and Day 31 | 
| Changes in fasting blood HbA1c | Fasting blood HbA1c will be examined in %. | Day 1 and Day 31 | 
| Changes in lipid metabolism | Triglyceride, cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol will be examined in mmol/L. | Day 1 and Day 31 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-of-1, plant-based diet, precision nutrition, continuous glucose monitoring, type 2 diabetes