Prevention of Diabetes in Overweight/Obese Preadolescent Children (PREDIKID)

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

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.

Study Overview

• Status: Completed
• Conditions: Overweight Children With Type 2 Diabetes Risk
• Intervention / Treatment: Behavioral: lifestyle and psycho-educational program; Other: Exercise plus lifestyle and psycho-educational program

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Araba
    • Vitoria-Gasteiz, Araba, Spain, 01009
      • Pediatric Endocrinology Unit of the University Hospital of Araba (HUA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Family-based lifestyle education and psycho-educational program	Behavioral: lifestyle and psycho-educational program; 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
Experimental: Exercise group; Supervised exercise plus family-based lifestyle education and psycho-educational program	Behavioral: lifestyle and psycho-educational program; 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; Other: Exercise plus lifestyle and psycho-educational program; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confounding variable: puberty stage	The pediatrician will evaluate Tanner staging by direct examination with breast palpation in girls and testicular measurement by orchidometer in boys.	Baseline
Confounding variable:physical activity and sleep	Children will wear an activity monitor on the wrist for 7 consecutive days for 24 hours to record physical activity intensity levels and patterns, as well as sleeping habits and participants will also complete a diary log	Baseline and at the end of the 22 weeks of intervention
Confounding variable: dietary habits	Dietary intake will be evaluated by two non-consecutive 24h recalls within a period of seven days by nutritionists and a validated food frequency questionnaire	Baseline and at the end of the 22 weeks of intervention
Confounding variable: sedentary behaviors	Sedentary behaviors such as watching television, playing computer games, playing video games or phone games, and surfing the Internet will be self-reported by the children using validated questionnaires	Baseline and at the end of the 22 weeks of intervention
Confounding variable: Socio-demographic variables:	Information about socioeconomic status, demographic characteristics and family medical history of obesity, diabetes, dyslipidemia and hypertension will be collected. Socioeconomic status will be evaluated using The Family Affluence Scale (74) and parental education level and parental occupation. As demographic characteristics date of birth, sex, ethnicity and family structure will be recorded.	Baseline

Collaborators and Investigators

• Sponsor: University of the Basque Country (UPV/EHU)
• Collaborators: Universidad Pública de Navarra; Ministerio de Economía y Competitividad, Spain

Publications and helpful links

General Publications

• Medrano M, Maiz E, Maldonado-Martin S, Arenaza L, Rodriguez-Vigil B, Ortega FB, Ruiz JR, Larrarte E, Diez-Lopez I, Sarasua-Miranda A, Tobalina I, Barrenechea L, Perez-Asenjo J, Kannengiesser S, Manhaes-Savio A, Echaniz O, Labayen I. The effect of a multidisciplinary intervention program on hepatic adiposity in overweight-obese children: protocol of the EFIGRO study. Contemp Clin Trials. 2015 Nov;45(Pt B):346-355. doi: 10.1016/j.cct.2015.09.017. Epub 2015 Sep 25.
• Arenaza L, Medrano M, Amasene M, Rodriguez-Vigil B, Diez I, Grana M, Tobalina I, Maiz E, Arteche E, Larrarte E, Huybrechts I, Davis CL, Ruiz JR, Ortega FB, Margareto J, Labayen I. Prevention of diabetes in overweight/obese children through a family based intervention program including supervised exercise (PREDIKID project): study protocol for a randomized controlled trial. Trials. 2017 Aug 10;18(1):372. doi: 10.1186/s13063-017-2117-y.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2017
• Primary Completion (Actual): September 15, 2018
• Study Completion (Actual): September 15, 2018

Study Registration Dates

• First Submitted: January 16, 2017
• First Submitted That Met QC Criteria: January 18, 2017
• First Posted (Estimate): January 23, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Diabetes Mellitus; Overweight
• Other Study ID Numbers: DEP2016-78377-R

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No