Clinical trial NCT05261373: Efficacy of a Nutritional Education Strategy and Physical Exercise on the Gut Microbiota in Type 2 Diabetics
Official title: Efficacy of a Nutritional Education Strategy and Role of Physical Exercise on the Modulation of Muscle Metabolism Through the Gut Microbiota in Type 2 Diabetics (THE EDUGUTION PROJECT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Cardiovascular Diseases
Fat Burn
Metabolism Disorder
Keywords: Gut microbiota
High intensity interval training
Insulin resistance
Diet
Fat metabolism
Lead sponsor: University of Cadiz
Sponsor class: OTHER
Collaborators: name: Ministerio de Ciencia e Innovación, Spain
First posted: 2022-03-02
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The project is a randomized controlled clinical trial with T2DM and obesity
Primary purpose: TREATMENT

Brief summary: We hypothesize that the combination of a nutritional education intervention with a HIIT-based physical exercise program improve muscle metabolism through positive modifications of gut microbiota in people with T2DM, leading to better glycaemia/insulinaemia levels, reduction of body fat mass and improving quality of life.

The project is a randomized controlled clinical trial in 120 participants with T2DM and obesity, which aims to determine the efficacy of a nutritional education program and the role of physical exercise type on health related variables. The participants will be of both sexes with age between 40 and 55 years, belonging to the Province of Cádiz. The design has two 12-week interventions; the main factor has 2 levels: participants who receive the nutritional education (EDU) and controls (CG); the second factor has 3 levels: high-intensity interval training (HIIT), moderate intensity continuous training (MICT), and controls (INACT). Therefore, participants will be randomized into 6 groups (n=20), adjusted by gender (≈50% in each group): EDU+HIIT, EDU+MICT, EDU+INACT, CG+HIIT, CG+MICT, CG+INACT.

The outcome variables, which will be measured before and after the intervention, will include: dietary intake assessment, physical activity assessment, quality of life, faecal samples, blood samples, blood pressure, appetite assessment, muscle biopsy samples, body composition and fluids, basal metabolism, maximal fat oxidation test and cardiorespiratory fitness.

Detailed description: Approximately 500 million people have Type 2 Diabetes Mellitus (T2DM) in 2018 and it is expected to increase between 20% and 50% over the next 10 years. T2DM is also called non-insulin-dependent or adult-onset, and it results from the body's ineffective use of insulin, being the result of excess body weight and physical inactivity. Diabetes is the 7 leading cause of death by increasing the risks of cardiovascular and other diseases, many of which (43%) occur prematurely and are largely preventable through adoption of policies to create supportive environments for healthy lifestyles.

Improving the implementation of health-related education programs is a key tool for behaviour change; however, not all education supports behavioural change. The terms education and knowledge are often thought of interchangeably. Nevertheless, while knowledge is defined as "facts, information, and skills acquired by a person through experience or education", education is a comprehensive term that can be defined as "the process of receiving or giving systematic instruction" or as "an enlightening experience". Therefore, interventions should attempt the education achievement in order to improve healthy lifestyles and reduce diabetes prevalence, complications and morbimortality. In this line, the impact of nutritional counselling on weight reduction, glycaemia control, and improve of health in obese and diabetes population have been previously study with inconsistent results. Thus, education strategies should be optimized to achieve behaviour changes related to nutrition and physical exercise.

Recently it has been discover than gut microbiota can modulate behaviour, including nutritional behaviour and decisions, therefore, gut microbiota can have an impact on the efficacy of an education program. Gut microbiota is composed of more than 100 billion microorganisms classified in at least 1000 different species of bacteria, fungi, viruses and yeasts. In light of these considerations, Nobel laureate Joshua Lederberg proposed to consider the microbiota, especially the intestinal one, as a "superorganism". One of the great findings in neuroscience is the connection of the intestinal microbiota and the brain, called gut-brain axis, telling us whether to eat or not, even what food (for example the desire to eat something sweet or salty). These results can be a great advance for the area of education and behavioural sciences, especially of those education program focused on improve nutritional habits.

Moreover, even maintaining similar energy intake through diet and similar physical activity levels, a healthy change of gut microbiota is able to reduce body fat percentage, what has a positive impact on the prevention and treatment of T2DM. Therefore, educational programs focused on improving gut microbiota can be a useful tool to respond to the Global Plan of Action on Non-communicable Diseases, and could reduce the failure of some weight loss educational strategies and programs. Recently it has been shown that gut microbiota plays a significant role in the pathophysiology of T2DM modulating the secretion of insulin and glucose. Therefore, tools that establish the microbiota should be promoted, such as nutritional restoration strategies, through prebiotics and probiotics, in obesity and T2DM populations as we have previously study.

In addition, physical exercise seems to improve gut microbiota composition, specifically the Firmicutes spp. / Bacteroidetes spp. ratio, additionally, a positive correlation has been found between Lactobacillus spp. and Bifidobacterium spp. with serum leptin levels in trained rats. Most exercise programs to combat obesity have been based primarily on aerobic exercises. Aerobic training is associated with a decrease in body fat mass, especially visceral fat mass, increases insulin sensitivity, lowers baseline glucose and insulin levels, and increases the expression of glucose and fatty acid transport proteins in muscle fibres. Workouts that are performed at the intensity at which the person burns more fat (FatMax) seems to reduce body fat and insulin resistance in older women with type 2 diabetes. However, the time taken for these training sessions is approximately 60-90 minutes a day.

According to previous scientific research, we hypothesize that the combination of a nutritional education intervention with a HIIT-based physical exercise program improve muscle metabolism through positive modifications of gut microbiota in people with T2DM, leading to better glycaemia/insulinaemia levels, reduction of body fat mass and improving quality of life.

The project is a randomized controlled clinical trial in 120 participants with T2DM and obesity, which aims to determine the efficacy of a nutritional education program and the role of physical exercise type on health related variables. The participants will be of both sexes with age between 40 and 55 years, belonging to the Province of Cádiz. The design has two 12-week interventions; the main factor has 2 levels: participants who receive the nutritional education (EDU) and controls (CG); the second factor has 3 levels: high-intensity interval training (HIIT), moderate intensity continuous training (MICT), and controls (INACT). Therefore, participants will be randomized into 6 groups (n=20), adjusted by gender (≈50% in each group): EDU+HIIT, EDU+MICT, EDU+INACT, CG+HIIT, CG+MICT, CG+INACT.

The outcome variables, which will be measured before and after the intervention, will include: dietary intake assessment, physical activity assessment, quality of life, faecal samples, blood samples, blood pressure, appetite assessment, muscle biopsy samples, body composition and fluids, basal metabolism, maximal fat oxidation test and cardiorespiratory fitness.

Eligibility criteria: Inclusion Criteria:

* Non smoking
* Non-alcoholic (\<3 standard drinks per day)
* Body mass index \>25 kg/m maintaining the habitual dietary patterns without a body mass reduction higher than 2% during the last 6 months
* Not being insulin dependent
* Absence of injury, disease or disability or other known medical condition which could affect the ability to successfully participate in physical exercise tests
* Absence of cardiovascular disease (angina, peripheral or cerebro-vascular disease, etc.).
* Absence of neurologic and psychiatric diseases.
* Absence of respiratory diseases (pulmonary hypertension, Chronic obstructive pulmonary disease, etc.).
* Absence of other metabolic diseases (hyper/hypo parathyroidism, hyper/hypothyroidism, Cushing's disease, Type 1 diabetes, etc.)
* Absence of active inflammatory bowel disease
* Absence of kidney disease
* Absence of tumours
* Absence of coagulation dysfunction
* Not under treatment with medications k known to affect glucose metabolism, recent steroid treatment (within 6 months), or hormone replacement therapy
* Be able to understand a communication in Spanish or English.

Exclusion Criteria:

* They do not attend more than 2 or 4 consecutive sessions of nutritional counselling or physical training respectively.
* The lose more than 4 or 6 sessions in total of nutritional counselling or physical training respectively.

Primary outcomes:
measure: Assessed gut microbiota population
timeFrame: 12 weeks
measure: Assessed changes in Insulin Resistance
timeFrame: 12 weeks
measure: Muscle biopsy samples: mRNA expression by quantitative real-time PCR (Transcriptomic)
timeFrame: 12 weeks
measure: Muscle biopsy samples: Western blot analysis (Proteomic)
timeFrame: 12 weeks
measure: Muscle biopsy samples: Citrate synthase (CS) activity assay (Mitochondrial content marker)
timeFrame: 12 weeks
measure: Assessed changes from Appetite assessment
timeFrame: 12 weeks
measure: Assessed changes from Body composition: Fatmass and Fat-free mass.
timeFrame: 12 weeks
Secondary outcomes:
measure: Assessed changes from dietary intake: Frequency of consumption
timeFrame: 12 weeks
measure: Assessed changes from dietary intakes: 24 hours dietary recalls
timeFrame: 12 weeks
measure: Assessed changes from accelerometry: Physical activity time
timeFrame: 12 weeks
measure: Assessed changes from physical activity
timeFrame: 12 weeks
measure: Assessed changes from resting fat oxidation
timeFrame: 12 weeks
measure: Assessed changes from cardiorespiratory fitness
timeFrame: 12 weeks
measure: Assessed changes from maximal fat oxidation
timeFrame: 12 weeks
measure: Assessed changes from self-reported quality of life
timeFrame: 12 weeks
measure: Assessed changes from blood pressure
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Puerto Real
country: Spain
facility: Facultad de Ciencias de la Educación
state: Cadiz
Study officials:
affiliation: University of Cádiz
name: Jesús Gustavo Ponce González, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cádiz
name: Cristina Casals, PhD
role: PRINCIPAL_INVESTIGATOR
References: