Therapeutic Strategies for Type 2 Diabetes Based on Lifestyle Changes: Plant-based Diet and Physical Exercise
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in Body Mass Index (BMI)
Study Overview
Brief Summary
The study evaluates the impact of a strict vegetarian diet combined with regular physical exercise and the use of probiotics on metabolic, inflammatory, and epigenetic parameters in patients with type 2 diabetes. It aims to determine the influence of these interventions on gut microbiota, glycemic control, body composition, insulin resistance, and quality of life.
Detailed Description
This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of a strict vegetarian diet (SVD) combined with regular physical exercise (RPE), with or without probiotic supplementation, on key metabolic and physiological parameters in patients with type 2 diabetes mellitus (T2DM). Participants will be monitored for changes in glycemic control, insulin resistance (IR), liver function (elastography and ultrasound), metabolomic profile, muscle composition (biopsy), cholesterol efflux, and gene expression.
Glycemic Control Glycemic control will be assessed through glycated hemoglobin (HbA1c), fasting glucose, fructosamine, and oral meal tolerance test (OMTT). A standardized dietary test (500 kcal plant-based meal) will be conducted at baseline and post-intervention, measuring postprandial glucose, insulin, proinsulin, C-peptide, and incretin hormones (GLP-1, GIP).
Insulin Resistance (IR) IR will be evaluated using HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and fasting insulin levels. The study will also analyze inflammatory markers (TNF-α, IL-1β, IL-6, IFN-γ), as chronic low-grade inflammation plays a crucial role in IR development.
Elastography and Ultrasound (US) Liver ultrasound and transient elastography (FibroScan®) will be performed to assess hepatic steatosis and fibrosis, which are highly prevalent in T2DM. The effects of dietary and probiotic interventions on liver fat content, liver stiffness, and metabolic liver function will be analyzed.
Metabolome Analysis Metabolomic profiling will be conducted through mass spectrometry-based analysis of fasting and postprandial plasma samples. The study will evaluate amino acids, lipids, short-chain fatty acids, bile acids, ketone bodies, and glycolysis-related metabolites to understand how dietary and microbiome changes influence metabolic pathways in T2DM.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 45 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have a medical diagnosis of type 2 diabetes for a maximum of 5 years.
- •Be omnivorous; Have a Body Mass Index (BMI) ≥ 25 kg/m2 and < 40 kg/m2;
- •Be between the ages of 45 and 70, both genders.
- •Women should be in the postmenopausal stage;
- •Use no more than three hypoglycemic medications in total;
- •Have the availability for a four-week consecutive hospitalization at CSVN.
Exclusion Criteria
- •Be using insulin, anti-obesity medications, antibiotics, and/or probiotic supplements in the 2 months preceding data collection;
- •Use of alcohol or tobacco;
- •Have limited mobility and a previous diagnosis of cardiopulmonary diseases;
- •Report current or previous (within the past two months) diarrhea during screening;
- •Have liver or kidney failure and uncontrolled endocrine disorders (hypothyroidism, hypogonadism, and adrenal insufficiency);
- •Have eating disorders or have undergone bariatric surgery.
Arms & Interventions
Strict Vegetarian Diet, Regular Physical Exercise, and Placebo Administration
Participants in this group will follow a strict vegetarian diet (SVD) combined with regular physical exercise (RPE) for four weeks. The diet will consist of plant-based foods rich in fiber and bioactive compounds, with a controlled macronutrient distribution. Physical activity will include structured aerobic and resistance exercises supervised by a physical educator. Instead of probiotic supplementation, participants will receive a placebo administered in the same manner as the probiotic group to ensure blinding.
Intervention: Placebo Administration (Dietary Supplement)
Strict Vegetarian Diet, Regular Physical Exercise, and Probiotic Supplementation
Participants in this group will receive the same strict vegetarian diet (SVD) and regular physical exercise (RPE) as Arm 1. In addition, they will take a probiotic supplement containing a combination of four different strains, administered twice daily for four weeks. This group aims to assess the potential additional metabolic benefits of probiotic supplementation in individuals with type 2 diabetes.
Intervention: Probiotic Supplementation (Dietary Supplement)
Outcomes
Primary Outcomes
Change in Body Mass Index (BMI)
Time Frame: Baseline and 4 weeks post-intervention
Body mass index (BMI) will be calculated from height and weight (weight in kg / height in m²) to assess the impact of the intervention on overall body weight regulation. This outcome reflects metabolic improvement and lifestyle adherence. Unit of Measure: kg/m²
Change in Waist, Abdominal, and Hip Circumference
Time Frame: Baseline and 4 weeks post-intervention
Waist, abdominal, and hip circumferences will be measured using a standardized flexible tape method. These anthropometric parameters are indicators of central fat distribution and associated cardiometabolic risk. Measurements will follow WHO recommendations. Unit of Measure: cm
Change in Waist-to-Hip Ratio (WHR)
Time Frame: Baseline and 4 weeks post-intervention
Waist-to-hip ratio (WHR) will be calculated by dividing waist circumference by hip circumference. This index is used to evaluate body fat distribution and the risk of metabolic disorders, particularly central obesity, in individuals with T2DM. Unit of Measure: Ratio (unitless)
Change in Functional Aerobic Capacity (1-Mile Walk Test)
Time Frame: Baseline and 4 weeks post-intervention
Aerobic capacity will be assessed using the 1-Mile Walk Test. Participants will be instructed to walk one mile as fast as possible on a flat surface, and the time to completion will be recorded. The objective is to evaluate improvements in cardiovascular endurance following the intervention. Unit of Measure: Time in minutes
Change in Functional Mobility (Up and Go Test)
Time Frame: Baseline and 4 weeks post-intervention
Functional mobility will be assessed using the "Up and Go" test. Participants will be timed as they rise from a seated position, walk three meters, turn around, walk back to the chair, and sit down. The test is used to detect improvements in balance, mobility, and lower-limb function in response to the intervention. Unit of Measure: Time in seconds
Change in Fasting Blood Glucose
Time Frame: Baseline and 4 weeks post-intervention
Fasting plasma glucose will be measured after 8-12 hours of fasting by glucose-oxidase method to evaluate improvements in basal glycemic levels. The goal is to determine whether the intervention improves glucose homeostasis in patients with T2DM. Unit of Measure: mg/dL
Change in Postprandial Glucose Levels
Time Frame: Baseline and 4 weeks post-intervention
Two-hour postprandial glucose will be measured using capillary or venous blood samples by glucose-oxidase method after a standardized meal. The goal is to evaluate improvements in glycemic response to food intake due to the intervention. Unit of Measure: mg/dL
Change in Glycated Hemoglobin (HbA1c)
Time Frame: Baseline and 4 weeks post-intervention
Glycated hemoglobin (HbA1c) levels will be measured in venous blood samples using HPLC to assess long-term glycemic control. The main hypothesis is that the combined intervention of a plant-based diet, physical exercise, and probiotics will significantly reduce HbA1c levels compared to baseline. Unit of Measure: % HbA1c
Secondary Outcomes
- Change in Incretin Hormone Levels (GLP-1 and GIP)(Baseline and 4 weeks post-intervention)
- Change in Liver Enzymes (AST, ALT, GGT)(Baseline and 4 weeks post-intervention)
- Change in Standard Lipid Profile(Baseline and 4 weeks post-intervention)
- HDL Function and Lipid Profile(Baseline and 4 weeks post-intervention)
- Change in C-Reactive Protein (CRP) Levels(Baseline and 4 weeks post-intervention)
- Change in Plasma Cytokine Levels(Baseline and 4 weeks post-intervention)
- Metabolomic and Biochemical Markers(Baseline and 4 weeks post-intervention)
- Change in expression of Metabolism- and Inflammation-Related microRNAs(Baseline and 4 weeks post-intervention)
- Change in Expression of Inflammatory Genes(Baseline and 4 weeks post-intervention)
- Change in Inflammatory Gene Expression in Lymphocytes and Skeletal Muscle(Baseline and 4 weeks post-intervention)
- Change in Fasting Insulin, Proinsulin, and C-Peptide Levels(Baseline and 4 weeks post-intervention)
- Change in Insulin Resistance Assessed by HOMA-IR(Baseline and 4 weeks post-intervention)
- Changes in Gut Microbiota Composition(Baseline and 4 weeks post-intervention)
- Change in Liver Steatosis Assessed by Abdominal Ultrasound(Baseline and 4 weeks post-intervention)
- Change in Liver Fat and Fibrosis Assessed by Transient Elastography(Baseline and 4 weeks post-intervention)
- Change in Depressive Symptoms Measured by the Beck Depression Inventory - Second Edition (BDI-II)(Baseline and 12 weeks post-intervention)
- Change in Diabetes-Specific Quality of Life Measured by the Diabetes Quality of Life Measure (DQOL)(Baseline and 12 weeks post-intervention)
- Change in General Well-Being Measured by the Q8RN Questionnaire(Baseline and 12 weeks post-intervention)
- Change in Fasting Glucose During Telemedicine Follow-Up(Every 3 months over a 12-month follow-up period after the intervention)
- Change in HbA1c Levels During Telemedicine Follow-Up(Every 3 months over a 12-month follow-up period after the intervention)
- Change in Lipid Profile During Telemedicine Follow-Up(Every 3 months over a 12-month follow-up period after the intervention)
- Change in Liver Enzymes During Telemedicine Follow-Up(Every 3 months over a 12-month follow-up period after the intervention)
Investigators
Maria Elizabeth Rossi da Silva
MD, PhD
University of Sao Paulo General Hospital