Therapeutic Strategies for Type 2 Diabetes Based on Lifestyle Changes: Plant-based Diet and Physical Exercise

Maria Elizabeth Rossi da Silva

Status: Enrolling

Conditions: Type 2 Diabetes Mellitus (T2DM); Insulin Resistance; Inflamation; Gut Microbiomes

Treatments: Dietary Supplement: Probiotic Supplementation; Dietary Supplement: Placebo Administration

Study type: Interventional

Funder types: Other

Identifiers

NCT06959043

Cappesq

Details and patient eligibility

About

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.

Full 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.

Muscle Biopsy A vastus lateralis muscle biopsy will be performed in a subgroup of participants (n=24). Samples will be analyzed for fiber composition, extracellular matrix remodeling, mitochondrial function, and inflammatory markers. The role of microRNAs (miR-29a, miR-29b, miR-1, miR-133a/b, miR-206) in muscle insulin sensitivity will also be investigated.

Cholesterol Efflux HDL functionality will be assessed by measuring cholesterol efflux capacity from macrophages exposed to participants' serum. This analysis will provide insight to cardiovascular risk modulation by diet and probiotics in T2DM.

Gene Expression Analysis Peripheral blood lymphocytes will be analyzed for expression of inflammation-related genes (TNF-α, IL-6, IL-1β, IFN-γ, TLR4, TLR5) and longevity-related genes (SIRT1, FOXO1, PGC-1α, P53). These markers will help determine how dietary and probiotic interventions influence immune response, cellular aging, and metabolic regulation.

Microbiota analysis This study will assess how a strict vegetarian diet and probiotic supplementation influence gut microbiota composition and functionality in individuals with T2DM. Stool samples will be collected before and after the intervention (4 weeks) and analyzed using 16S rRNA sequencing (NGS platforms: Ion Torrent PGM or Illumina MiSeq).

Microbiota diversity (alpha and beta diversity metrics) and the relative abundance of key bacterial taxa (Bacteroides, Firmicutes, Akkermansia, Prevotella, Bifidobacterium, Lactobacillus) will be evaluated. Functional analysis will include metagenomic predictions (PICRUSt2), short-chain fatty acid (SCFA) production, and microbial metabolic pathways.

The impact of probiotic supplementation (B. breve BR03, B. breve B632, B. longum 04, L. reuteri LRE11) will be assessed by comparing gut microbiota changes between the probiotic and placebo groups, focusing on butyrate-producing bacteria, lactate-utilizing species, and intestinal barrier integrity markers.

The intervention will last four weeks, followed by 12 months of telemedicine follow-up. This study aims to provide new insights into the role of lifestyle interventions in metabolic regulation, inflammation, and gut microbiota modulation in T2DM, potentially offering novel therapeutic strategies beyond pharmacological approaches.

Enrollment: 60 estimated patients

Sex: All

Ages: 45 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Strict Vegetarian Diet, Regular Physical Exercise, and Placebo Administration

Placebo Comparator group

Description:

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.

Treatment:

Dietary Supplement: Placebo Administration

Strict Vegetarian Diet, Regular Physical Exercise, and Probiotic Supplementation

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Probiotic Supplementation