Bioenergetics and Metabolism in Pediatric Populations

Study Overview
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Brief Summary
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The investigators want to learn more about obesity, the development of insulin resistance, and Type 2 Diabetes in children. The investigators will do this through collecting information about children's health and conducting experiments on a variety of samples.

Official Title
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Bioenergetics and Metabolism in Pediatric Populations

Conditions
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Obesity, Type 2 Diabetes Mellitus, Insulin Resistance

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 5-9 years and Tanner stage as reported by parent no greater than stage 1 OR Age 5 years - 17 years 5 months, diagnosed with type 2 diabetes mellitus or insulin resistance Either healthy lean (BMI≥ 5th percentile and <85th percentile for age/sex) or obese (BMI ≥ 95th percentile for age/sex) For those with BMI≥ 95th percentile for age/sex, parental verbal confirmation will be obtained that the child had a history of BMI≥ 95th percentile for age/sex for at least six months prior to study enrollment Exclusion criteria: Genetic or physical conditions impacting mobility over past year as determined by the Principal Investigator (PI) Having known chronic illnesses/disorders that may independently affect study outcome measures: type 1 diabetes mellitus, neurologic (e.g. epilepsy), developmental (developmental delay, autism spectrum disorder), endocrine (thyroid, Cushing's), hepatic, autoimmune, cardiac and renal disorders. Also, chronic lung disorders except well controlled asthma that does not require permanent use of inhaled/oral steroids Taking any of the following medications that can affect study outcome: antipsychotics, thyroid hormone replacement therapy, inhaled/oral steroids, insulin, anabolic drugs (growth hormone replacement therapy and oxandrolone) and stimulants BMI<5th percentile for age/sex (classified as underweight based on Centers for Disease Control and Prevention growth charts) Subjects determined ineligible by the PI.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Lean<br>Healthy lean individuals (n=20) defined with a Body Mass Index (BMI) ≥ 5th percentile and <85th percentile for age/sex will be recruited. Participants in this cohort will be asked to complete a one-time study visit. | |
| Healthy Obese<br>Healthy obese individuals (n=20) defined with a Body Mass Index (BMI) ≥ 95th percentile for age/sex will be recruited. Participants in this cohort will be asked to complete a one-time study visit. | |
| Obese Insulin Resistant<br>Obese insulin resistant individuals (n=70) as defined with a Body Mass Index (BMI) ≥ 95th percentile for age/sex and will be recruited. Participants will be asked to complete a total of 2 study visits. The second study visit will occur at 12 months (± 2 weeks) after the initial study visit. | |
| Type 2 Diabetes or Insulin Resistant<br>Obese individuals with Type 2 Diabetes or insulin resistance (n=20) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Altered circulating blood cell bioenergetics | The investigators hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will exhibit altered circulating blood cell bioenergetics. | After completion of all study visits, approximately 2 years. | 
| Oxidized plasma redox state | The investigators hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will exhibit a more oxidized plasma redox state. | After completion of all study visits, approximately 2 years. | 
| Alterations in resting energy expenditure | The investigators hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will be associated with alterations of decreased resting energy expenditure. | After completion of all study visits, approximately 2 years. | 
| Alterations in fatty acid oxidation | We hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will be associated with alterations of impaired fatty acid oxidation (FAO). | After completion of all study visits, approximately 2 years. | 
| Poor oxidative capacity | The investigators hypothesize that poor oxidative capacity over time may distinguish between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) phenotypes. | After completion of all study visits, approximately 2 years. | 
| Predicting Type 2 Diabetes development | The investigators hypothesize that poor oxidative capacity over time may be predictive of Type 2 Diabetes development. | After completion of all study visits, approximately 2 years. | 
| Bioenergetics in Type 2 Diabetes with metformin | The investigators hypothesize that the change in bioenergetics will be improved in obese Type 2 Diabetes children at 6 months of metformin therapy that will be prescribed as part of their clinical care. | 6 months | 
| Resting Energy Expenditure in Type 2 Diabetes with metformin | The investigators hypothesize that the change in resting energy expenditure will be improved in obese Type 2 Diabetes children at 6 months of metformin therapy that will be prescribed as part of their clinical care. | 6 months | 
| Fatty Acid Oxidation in Type 2 Diabetes with metformin | The investigators hypothesize that the change in fatty acid oxidation will be improved in obese Type 2 Diabetes children at 6 months of metformin therapy that will be prescribed as part of their clinical care. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Pediatric Health, Type 2 Diabetes, Insulin Resistance, Metformin Therapy