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

NCT05259449 | Completed

• 2 other identifiers: The APETEX projectPID2020-120034RA-I00/AEI/10.13
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 1

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 prediabetes or type 2 diabetes (T2D), and overweight or 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, D-HIIT. Participants did:
• Underwent a 12-week intervention within their assigned group.
• Visited the research facilities three times per week if assigned to an exercise group, or once every two weeks if in a diet group.

Conditions

Diabetes Mellitus, Type 2

Keywords

Insulin Sensitivity; Appetite regulation; aerobic exercise; Extracellular vesicles

Outcome Measures

Primary Outcomes (1)

• Glycated hemoglobin

  Glycated hemoglobin (HbA1c, %) was measured using high-performance liquid chromatography (HPLC) with the automated ADAMS™ HA-8180V analyzer (ARKRAY, Kyoto, Japan).

  Pre and Post the 12-week Intervention

Secondary Outcomes (30)

• Assessed changes in Glucose concentration

  Pre and Post the 12-week intervention

• Assessed changes in Insulin concentration

  Pre and Post the 12-week intervention

• Assessed changes in Appetite assessment.

  Pre and Post the 12-week intervention

• Assessed changes in task of emotional reactivity to food images

  Pre and Post the 12-week intervention

• Assessed changes in Appetite hormones

  Pre and Post the 12-week intervention

Study Arms (6)

ND-INACT

NO INTERVENTION

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

Moderate-intensity continuous training (ND-MICT)

ACTIVE COMPARATOR

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

Other: Moderate-intensity continuous training (MICT)

High-intensity interval training (ND-HIIT)

ACTIVE COMPARATOR

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

Other: High-intensity interval training (HIIT)

Nutritional Intervention (D-INACT)

ACTIVE COMPARATOR

Participants who received nutritional intervention but not an exercise program.

Behavioral: Nutritional Intervention

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

EXPERIMENTAL

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

Behavioral: Nutritional Intervention; Other: Moderate-intensity continuous training (MICT)

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

EXPERIMENTAL

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

Behavioral: Nutritional Intervention; Other: High-intensity interval training (HIIT)

Interventions

Nutritional Intervention 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 mildly calorie-restricted diet (-250-500 kcal/day deficit), 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 or 5 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 (D-INACT); Nutritional Intervention High-intensity interval training (D-HIIT); Nutritional Intervention Moderate-intensity continuous training (D-MICT)

High-intensity interval training (HIIT) 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% of maximal HR and at least five did not reach 90% of maximal HR. Participants were asked to maintain a cadence above 80RPM.

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

Moderate-intensity continuous training (MICT) 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 (TL) 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 TL 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. The TL 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.

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

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of type 2 diabetes or prediabetes (HbA1c ≥ 5.7%)
• No history of substance abuse (tobacco, alcohol, or other drugs).
• Body mass index ≥25 kg/m², maintaining habitual dietary patterns with stable body weight for at least 6 months
• Stable physical activity and medication regimen for at least 6 months
• Lack of habitual vigorous-intensity physical activity and the presence of sedentary behavior characterized by prolonged sitting time (screening using the International Physical Activity Questionnaire short form).
• 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 tumors 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 communication in Spanish or English.
• Not pregnant

You may not qualify if:

• Failure to attend more than 2 consecutive sessions 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

Sponsors & Collaborators

• University of Cadiz: lead
• Ministerio de Ciencia e Innovación, Spain: collaborator

Study Sites (1)

Science of Education Faculty

Puerto Real, Cadiz, 11510, Spain

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

High-Intensity Interval Training

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Cristina Casals, PhD

  University of Cadiz

  PRINCIPAL INVESTIGATOR

• Jesús Ponce González, PhD

  University of Cadiz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the intervention, participants and intervention providers can not be blinded. However, outcome assessors and statisticians remained blinded to group allocation. Additionally, the randomization procedure was administered by an independent researcher.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The project is a randomized controlled clinical trial in individuals with prediabetes or type 2 diabetes, and overweight or obesity

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: February 28, 2022
• Study Start: March 10, 2022
• Primary Completion: December 10, 2025
• Study Completion: December 10, 2025
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)