Efficacy of Educational Nutrition and Exercise on the Regulation of Appetite Through Exosomes in Type 2 Diabetics

NCT ID: NCT05259449

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-10
• Study Completion Date: 2025-12-10

Brief Summary

The aim of this randomized controlled trial is to investigate the effects of different aerobic modalities; moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), and a nutritional intervention (D) on appetite regulation, appetite-related hormones, neural responses to food cues (EEG), and exosome-derived molecular signals in patients with type 2 diabetes (T2D) and obesity. It will also examine whether these effects differ between men and women.

The main questions it aims to answer are:

• What is the isolated and combined effect of these exercise modalities and diet on glucose metabolism, insulin dynamics, miRNA exosomal expression, appetite hormones, and neural responses to food stimuli?
• Is there a sex-specific best combination choice for improving appetite regulation and metabolic control?
• Are changes in miRNA exosomal profile, appetite-related hormones, and EEG-based neural responses associated with other health-related outcomes such as body composition, fat mass reduction, insulin sensitivity, physical condition, and quality of life?

To answer these questions, researchers designed a two-factor study. One factor was diet, with two levels Diet (D) and no diet (ND). The second factor was exercise, with three levels (inactive (INACT), MICT, and HIIT). Participants were randomly allocated into six groups: ND-INACT, ND-MICT, ND-HIIT, D-INACT, D-MICT, and D-HIIT.

Participants will:

• Undergo a 12-week intervention within their assigned group.
• Visit the research facilities three times per week if assigned to an exercise group, or once every two weeks if in a diet group.

Detailed Description

This randomized controlled trial is conducted in the Province of Cádiz (Spain). A total of 146 participants with type 2 diabetes (T2D) and obesity were enrolled and underwent baseline and post-intervention assessments of the study outcomes. Immediately after baseline evaluations, participants were randomly allocated to one of the six study groups. Randomization was stratified by sex to ensure approximately 50% of participants in each group were women. All participants received detailed written and verbal information about the study objectives, procedures, benefits, and potential risks before providing written informed consent. The study complied with the Declaration of Helsinki and was approved by the Research Ethics Committee of Cádiz (registration number 92.21; PEIBA number 1026-N-21) and by the Coordinating Committee for Biomedical Research Ethics of Andalusia (registration number 92.21; PEIBA number 1026-N-21; internal codes SICEIA-2025-001870 and SICEIA-2025-000778).

At both baseline and post-intervention, participants attended the research facilities in the morning following an overnight fast and were instructed to maintain their usual lifestyle while avoiding alcohol, caffeine, and strenuous physical activity for the specified periods prior to testing. During these visits, a comprehensive set of assessments was conducted to capture the effects of the interventions across multiple domains. These included measures of glucose metabolism, insulin dynamics, plasma exosomal miRNA expression, appetite-regulating hormones, neural responses to food cues, subjective appetite, body composition, dietary intake and adherence, physical activity and sedentary behavior, resting and maximal fat oxidation, cardiorespiratory fitness, blood pressure, and self-reported quality of life. Post-intervention assessments followed the same protocol, with participants in exercise groups completing their final training session at least 72 hours before testing. This design allows evaluation of both the isolated and combined effects of exercise and diet interventions on physiological, molecular, behavioral, and lifestyle outcomes, as well as potential sex-specific differences in response.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

ND-INACT

Participants who do not receive either nutritional intervention or an exercise program. They will be instructed to maintain their normal life habits with respect to physical activity and diet.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Moderate-intensity continuous training (ND-MICT)

Participants who do not receive nutritional intervention but are enrolled in a moderate-intensity continuous training exercise program.

Group Type: ACTIVE_COMPARATOR

Moderate-intensity continuous training (MICT)

Intervention Type: OTHER

Participants assigned to the MICT completed 3 weekly sessions, with 1-2 days of rest between sessions, on a cycle ergometer for 12 weeks. The MICT program consisted of 50 minutes of continuous pedaling at an intensity approximately 10 % above the lactate threshold, with cadence maintained between 60-80 rpm. The training load was increased by 10% if these two conditions were met: 1) no increase of at least 2 beats of heart rate from minute 20 to minute 40 of the training session, and 2) lactate levels below 2 mmol/L in minute 48 of the session. The training load for the first session was determined by an adjustment test consisting of an incremental test with five consecutive 10-minute phases at a constant cadence (60-80 RPM) from 90% to 130% of the ventilatory threshold power, calculated from the FatOx test data, with 10% increments in each step. was determined by the phase in which HR increased by ≥ 3 beats between phases and blood lactate levels increased by ≥ 1 mmol/L between phases.

High-intensity interval training (ND-HIIT)

Participants who do not receive nutritional intervention but are enrolled in a high-intensity interval training exercise program.

Group Type: ACTIVE_COMPARATOR

High-intensity interval training (HIIT)

Intervention Type: OTHER

Participants assigned to the HIIT completed 3 weekly sessions, with 1-2 days of rest between sessions, on a cycle ergometer for 12 weeks. The training load (TL) was determined from an incremental test until volitional exhaustion with one-minute work intervals (from 85% to 165% of maximal power output during VO2max test \[Wmax\] and with 10% increments) separated by 1.5-minute rest periods (at 20% Wmax). The program consisted of a 3 minutes warm-up with the first 2 minutes at 20% and last minute at 40% of the TL, followed by 10 series of 1 min duration at 90% of TL, with 1 minute of rest between sets at 20% of TL and ending with 2 minutes of cool-down at 20% of TL (estimated total time of the session: 25 minutes). A 5% increase in workload was applied when, for two consecutive sessions, the first three intervals failed to exceed 85%, and the last five did not reach 90% of maximal HR. Participants were asked to maintain a cadence above 80RPM.

Nutritional Intervention (D-INACT)

Participants who receive nutritional intervention but not an exercise program.

Group Type: ACTIVE_COMPARATOR

Nutritional Intervention

Intervention Type: BEHAVIORAL

The nutritional intervention was conducted through biweekly (± 3 days) in-person consultations with a nutritionist or dietitian. Firstly, the patient's diet was analyzed. Then, participants were guided to follow a Mediterranean pattern-based and mildly calorie-restricted diet, with the primary goal of achieving a 5 % reduction in body weight and reducing blood glucose levels. Meal plans were created using Nutrium® software , personalized to each participant's lifestyle and food preferences, and reviewed at each biweekly consultation. The dietary plan included at least 4 meals per day, ensuring a well-distributed intake of carbohydrates, a balanced distribution of macro- and micronutrients, and the inclusion of foods rich in prebiotics and probiotics. Moreover, some suggestions about the combination of foods and culinary techniques were provided. Only one session through the intervention was allowed to be attended telephonically.

Nutritional Intervention Moderate-intensity continuous training (D-MICT)

Participants who receive nutritional intervention and are enrolled in a moderate-intensity continuous training exercise program.

Group Type: EXPERIMENTAL

Nutritional Intervention

Intervention Type: BEHAVIORAL

The nutritional intervention was conducted through biweekly (± 3 days) in-person consultations with a nutritionist or dietitian. Firstly, the patient's diet was analyzed. Then, participants were guided to follow a Mediterranean pattern-based and mildly calorie-restricted diet, with the primary goal of achieving a 5 % reduction in body weight and reducing blood glucose levels. Meal plans were created using Nutrium® software , personalized to each participant's lifestyle and food preferences, and reviewed at each biweekly consultation. The dietary plan included at least 4 meals per day, ensuring a well-distributed intake of carbohydrates, a balanced distribution of macro- and micronutrients, and the inclusion of foods rich in prebiotics and probiotics. Moreover, some suggestions about the combination of foods and culinary techniques were provided. Only one session through the intervention was allowed to be attended telephonically.

Moderate-intensity continuous training (MICT)

Intervention Type: OTHER

Participants assigned to the MICT completed 3 weekly sessions, with 1-2 days of rest between sessions, on a cycle ergometer for 12 weeks. The MICT program consisted of 50 minutes of continuous pedaling at an intensity approximately 10 % above the lactate threshold, with cadence maintained between 60-80 rpm. The training load was increased by 10% if these two conditions were met: 1) no increase of at least 2 beats of heart rate from minute 20 to minute 40 of the training session, and 2) lactate levels below 2 mmol/L in minute 48 of the session. The training load for the first session was determined by an adjustment test consisting of an incremental test with five consecutive 10-minute phases at a constant cadence (60-80 RPM) from 90% to 130% of the ventilatory threshold power, calculated from the FatOx test data, with 10% increments in each step. was determined by the phase in which HR increased by ≥ 3 beats between phases and blood lactate levels increased by ≥ 1 mmol/L between phases.

Nutritional Intervention High-intensity interval training (D-HIIT)

Participants who receive nutritional intervention and are enrolled in a high-intensity interval training exercise program.

Group Type: EXPERIMENTAL

Nutritional Intervention

Intervention Type: BEHAVIORAL

The nutritional intervention was conducted through biweekly (± 3 days) in-person consultations with a nutritionist or dietitian. Firstly, the patient's diet was analyzed. Then, participants were guided to follow a Mediterranean pattern-based and mildly calorie-restricted diet, with the primary goal of achieving a 5 % reduction in body weight and reducing blood glucose levels. Meal plans were created using Nutrium® software , personalized to each participant's lifestyle and food preferences, and reviewed at each biweekly consultation. The dietary plan included at least 4 meals per day, ensuring a well-distributed intake of carbohydrates, a balanced distribution of macro- and micronutrients, and the inclusion of foods rich in prebiotics and probiotics. Moreover, some suggestions about the combination of foods and culinary techniques were provided. Only one session through the intervention was allowed to be attended telephonically.

High-intensity interval training (HIIT)

Intervention Type: OTHER

Participants assigned to the HIIT completed 3 weekly sessions, with 1-2 days of rest between sessions, on a cycle ergometer for 12 weeks. The training load (TL) was determined from an incremental test until volitional exhaustion with one-minute work intervals (from 85% to 165% of maximal power output during VO2max test \[Wmax\] and with 10% increments) separated by 1.5-minute rest periods (at 20% Wmax). The program consisted of a 3 minutes warm-up with the first 2 minutes at 20% and last minute at 40% of the TL, followed by 10 series of 1 min duration at 90% of TL, with 1 minute of rest between sets at 20% of TL and ending with 2 minutes of cool-down at 20% of TL (estimated total time of the session: 25 minutes). A 5% increase in workload was applied when, for two consecutive sessions, the first three intervals failed to exceed 85%, and the last five did not reach 90% of maximal HR. Participants were asked to maintain a cadence above 80RPM.

Interventions

Nutritional Intervention

The nutritional intervention was conducted through biweekly (± 3 days) in-person consultations with a nutritionist or dietitian. Firstly, the patient's diet was analyzed. Then, participants were guided to follow a Mediterranean pattern-based and mildly calorie-restricted diet, with the primary goal of achieving a 5 % reduction in body weight and reducing blood glucose levels. Meal plans were created using Nutrium® software , personalized to each participant's lifestyle and food preferences, and reviewed at each biweekly consultation. The dietary plan included at least 4 meals per day, ensuring a well-distributed intake of carbohydrates, a balanced distribution of macro- and micronutrients, and the inclusion of foods rich in prebiotics and probiotics. Moreover, some suggestions about the combination of foods and culinary techniques were provided. Only one session through the intervention was allowed to be attended telephonically.

Intervention Type: BEHAVIORAL

High-intensity interval training (HIIT)

Participants assigned to the HIIT completed 3 weekly sessions, with 1-2 days of rest between sessions, on a cycle ergometer for 12 weeks. The training load (TL) was determined from an incremental test until volitional exhaustion with one-minute work intervals (from 85% to 165% of maximal power output during VO2max test \[Wmax\] and with 10% increments) separated by 1.5-minute rest periods (at 20% Wmax). The program consisted of a 3 minutes warm-up with the first 2 minutes at 20% and last minute at 40% of the TL, followed by 10 series of 1 min duration at 90% of TL, with 1 minute of rest between sets at 20% of TL and ending with 2 minutes of cool-down at 20% of TL (estimated total time of the session: 25 minutes). A 5% increase in workload was applied when, for two consecutive sessions, the first three intervals failed to exceed 85%, and the last five did not reach 90% of maximal HR. Participants were asked to maintain a cadence above 80RPM.

Intervention Type: OTHER

Moderate-intensity continuous training (MICT)

Participants assigned to the MICT completed 3 weekly sessions, with 1-2 days of rest between sessions, on a cycle ergometer for 12 weeks. The MICT program consisted of 50 minutes of continuous pedaling at an intensity approximately 10 % above the lactate threshold, with cadence maintained between 60-80 rpm. The training load was increased by 10% if these two conditions were met: 1) no increase of at least 2 beats of heart rate from minute 20 to minute 40 of the training session, and 2) lactate levels below 2 mmol/L in minute 48 of the session. The training load for the first session was determined by an adjustment test consisting of an incremental test with five consecutive 10-minute phases at a constant cadence (60-80 RPM) from 90% to 130% of the ventilatory threshold power, calculated from the FatOx test data, with 10% increments in each step. was determined by the phase in which HR increased by ≥ 3 beats between phases and blood lactate levels increased by ≥ 1 mmol/L between phases.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of T2D or prediabetes (HbA1c ≥ 5.7%)
• No history of substance abuse (tobacco, alcohol, or other drugs).
• Body mass index >25 kg/m², maintaining the habitual dietary patterns with stable body weight for at the least 6 months
• Stable physical activity and medication regimen for at least 6 months
• Not insulin-dependent
• Absence of injury, disease, disability, or other known medical condition which could affect the ability to successfully participate in physical exercise tests
• Absence of tumours and cancer disease
• Absence of other pathologies that could affect the study outcomes.
• Not under medication regimen that could affect the study outcomes.
• Being able to understand a communication in Spanish or English.
• Not pregnant

Exclusion Criteria

• Failure to attend more than 2 consecutive or a total of 4 sessions of nutritional intervention.
• Failure to attend more than 4 consecutive or a total of 6 sessions of physical training.
• Serious injury
• Voluntary withdrawal
• Increased dose of diabetes medication

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministerio de Ciencia e Innovación, Spain

OTHER_GOV

Sponsor Role: collaborator

University of Cadiz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristina Casals, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cadiz

Jesús Ponce González, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cadiz

Locations

Science of Education Faculty

Puerto Real, Cadiz, Spain

Countries

Spain

Other Identifiers

PID2020-120034RA-I00/AEI/10.13

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

The APETEX project

Identifier Type: -

Identifier Source: org_study_id