Prevention of Diabetes in Overweight/Obese Preadolescent Children

Study Overview
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Brief Summary
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Background: The global pandemic obesity has led to increased risk for prediabetes and type 2 diabetes (T2D). Objectives: (i) To evaluate the effect of a 22 weeks multidisciplinary intervention program including exercise on T2D risk in pre-adolescents with high risk to develop T2D, and (ii) To identify the profile of microRNA in circulating exosomes and in blood peripheral mononuclear cells in pre-adolescents with high risk to develop T2D and its response to a multidisciplinary intervention program including exercise.

Detailed Description
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Background: The global pandemic obesity has led to increased risk for prediabetes and type 2 diabetes (T2D). Objectives: (i) To evaluate the effect of a 22 weeks multidisciplinary intervention program including exercise on T2D risk in pre-adolescents with high risk to develop T2D, and (ii) To identify the profile of microRNA in circulating exosomes and in blood peripheral mononuclear cells in pre-adolescents with high risk to develop T2D and its response to a multidisciplinary intervention program including exercise. Design, participants and methods: A total of 84 children with high risk of type 2 diabetes mellitus aged 8-12 years will be included and randomly assigned to control (N=42) or intervention (N=42) groups. The control group will receive a family-based lifestyle education and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week). The duration of training sessions will be 90 min of exercise, including warm-up, moderate to vigorous aerobic activities, and strength exercises. The following measurements will be evaluated at baseline prior to randomization and after the intervention: fasting, insulin glucose, and hemoglobin A1c; total and abdominal fat (dual X-ray absorptiometry); pancreatic, hepatic and visceral fat (magnetic resonance imaging); systolic and diastolic blood pressure; fasting leptin, adiponectin, fibroblast growth factor-21, fetuin-A, hs-C-reactive protein, tumor necrosis factor-alfa, interleukin (IL)-1beta and IL-6 and lipid profile; carotid intima-media thickness (ultrasonography), microRNA expression in circulating exosomes and in blood peripheral mononuclear cells (MiSeq-Illumina); functional peak aerobic capacity (cardiopulmonary exercise testing and 20m shuttle run test). Changes in dietary habits (food frequency questionnaire and two non-consecutive 24h recalls), physical activity and sleep (accelerometry); sex, age, socioeconomic status and pubertal status will be used as potential confounders. Discussion/Conclusions: Early prevention and identification of children with high risk to develop T2D could help to reduce the morbidity and mortality associated with the disease.

Official Title
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Prevention of Diabetes in Overweight/Obese Preadolescent Children Through a Family-based Intervention Program Including Supervised Exercise; the PREDIKID Study

Conditions
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Overweight Children With Type 2 Diabetes Risk

Intervention / Treatment
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* Behavioral: lifestyle and psycho-educational program
* Other: Exercise plus lifestyle and psycho-educational program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight/obese children aged between 8 and 12 years, meeting the international criteria for classification for T2D risk and having at least one parent or caregiver willing to participate in the program sessions will be included Exclusion Criteria: Children with any medical condition that could affect the results of the study or that limits physical activity will be excluded

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Family-based lifestyle education and psycho-educational program | Behavioral: lifestyle and psycho-educational program<br>* The family-based healthy lifestyle education and psychological education program will be followed once every two weeks (11 sessions over 22 weeks) for 90 minutes (45 minutes in the healthy lifestyle education program and 45 minutes in the psycho-educational intervention). The sessions of the healthy lifestyle education and psycho-educational interventions will be developed simultaneously and delivered to both parents (or caregivers) and children, separately. The family-based healthy lifestyle education program will be conducted by experienced nutritionists and the psycho-educational program by experienced psychologists in behavior changes<br>|
| Experimental: Exercise group<br>Supervised exercise plus family-based lifestyle education and psycho-educational program | Behavioral: lifestyle and psycho-educational program<br>* The family-based healthy lifestyle education and psychological education program will be followed once every two weeks (11 sessions over 22 weeks) for 90 minutes (45 minutes in the healthy lifestyle education program and 45 minutes in the psycho-educational intervention). The sessions of the healthy lifestyle education and psycho-educational interventions will be developed simultaneously and delivered to both parents (or caregivers) and children, separately. The family-based healthy lifestyle education program will be conducted by experienced nutritionists and the psycho-educational program by experienced psychologists in behavior changes<br>Other: Exercise plus lifestyle and psycho-educational program<br>* The intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program. The exercise group will do exercise 3 days/week, 90 minutes per session, over a 22-week period. The program will be offered to the families five days per week to choose a total of three days/week. Sessions will be designed and supervised by exercise specialists. The duration of training sessions will be 90 minutes of exercise, including warm-up, moderate to vigorous aerobic activities, and strength exercises<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | The Homeostasis model assessment index will be calculated as fasting insulin concentration (microU/mL) x fasting glucose concentration (mmol/L)/22.5. | Baseline and at the end of the 22 weeks of intervention | 
| microRNA expression in circulating exosomes and in blood peripheral mononuclear cells | The expression of miRNAs will be measured in circulating exosomes and in white blood cells (MiSeq-Ilumina) | Baseline and at the end of the 22 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ectopic fat: pancreatic and liver fat accumulation | Hepatic and pancreatic fat will be measured by magnetic resonance | Baseline and at the end of the 22 weeks of intervention | 
| Total, abdominal and visceral adiposity | Total and abdominal adiposity will be measured by dual energy X-ray absorptiometry. Visceral adiposity will be measured by magnetic resonance imaging | Baseline and at the end of the 22 weeks of intervention | 
| Anthropometry and blood pressure | Body mass, height and waist circumference will be measured following standard protocols at least twice until consistent measures will be obtained and thereafter, body mass index (BMI) and waist to height ratio will be calculated. Systolic and diastolic blood pressure measurements will be performed following the recommendations for children using an arm blood pressure oscillometric monitor device | Baseline and at the end of the 22 weeks of intervention | 
| Cardiorespiratory fitness | Cardiorespiratory fitness will be assessed by two different tests: (i) The 20m shuttle run test in which the equation reported by Léger et al. will be used to estimate the maximum oxygen consumption (VO2max, ml/kg/min) from the 20m shuttle run test scores, and (ii) Direct cardiopulmonary exercise progressive incremental treadmill test using the modified American College of Sports Medicine protocol with respiratory gas analysis to exhaustion | Baseline and at the end of the 22 weeks of intervention | 
| Carotid intima-media thickness | carotid intima-media thickness will be measured by ultrasound according to international recommendations. | Baseline and at the end of the 22 weeks of intervention | 
| Inflammation and biochemical cardiovascular disease risk factors | Fasting lipid profile (total-, HDL- and LDL-cholesterol, and triglycerides), glucose, insulin, and hemoglobin A1c, cytokines (e.g. tumor necrosis factor alpha and IL-6) adipokines (e.g leptin and adiponectin), hepatokines (fetuin-A and fibroblast growth factor-21), liver enzymes (alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase), C-reactive protein, thyroid hormones (thyroid stimulating hormone, triiodothyronine and free thyroxine), urea, bilirubin and uric acid | Baseline and at the end of the 22 weeks of intervention |