Mitochondrial Function in Pediatric Obesity
The prevalence of pediatric obesity is increasing at an unprecedented rate. Obese children are at risk for the development of insulin resistance, relative insulin deficiency and type 2 diabetes mellitus. However, the cause of insulin resistance remains an area of scientific interest. The study of type 2 diabetes in children is limited by the lack of a non-invasive method to evaluate insulin resistance. Recent studies have suggested that mitochondrial dysfunction is associated with, and perhaps predictive of insulin resistance in adult relatives of individuals with type 2 diabetes. Mitochondria generate energy in muscle tissue through the production of ATP, and are important in the metabolism of both glucose and fat. This study evaluates a novel, non invasive, safe method for predicting insulin resistance and diabetes in children using a magnetic resonance imaging (MRI) based technique to measure mitochondrial function. We propose to investigate mitochondrial function and glucose metabolism in obese and non-obese children in early, mid and late puberty. Analyses will be conducted to investigate the presence of mitochondrial dysfunction in obese children, to evaluate the contribution of mitochondrial dysfunction to insulin resistance, and to determine the contribution of pubertal status to mitochondrial dysfunction and insulin resistance. The successful completion of this study would provide evidence to support the hypothesis that mitochondrial dysfunction plays a role in insulin resistance and diabetes in children. In addition, it would provide a new technique for the prediction of disease states and perhaps lead to the development of preventative therapeutics for insulin resistance and type 2 diabetes in children.
We hypothesize that mitochondrial dysfunction will mirror the progression of insulin resistance and precede and predict abnormal glucose metabolism in a population with pediatric obesity
Description
Aim I: A cross sectional study to evaluate baseline mitochondrial function in obese children compared to non-obese children. Determine whether children with pediatric obesity have impaired mitochondrial function based on 31P magnetic resonance spectroscopy when compared to healthy non-obese control children.Examine the relationship between mitochondrial function and insulin resistance in obese and non-obese children. Determine the impact of pubertal stage on mitochondrial function in obese and non-obese children.
Aim II:A prospective evaluation to determine in a longitudinal cohort study the timing and relationship of mitochondrial dysfunction to the development of insulin resistance in prepubertal/early pubertal obese children compared to prepubertal/early pubertal non-obese children. Determine in a longitudinal cohort study if obese children with mitochondrial dysfunction develop greater insulin resistance and/or impaired glucose tolerance at an earlier time point. Evaluate the relationship of obesity, timing of puberty and related changes in hormone levels to mitochondrial function and the development of insulin resistance and/or impaired glucose tolerance in longitudinal analyses.
Status: Recruiting (N/A). Started on June 1st, 2007.
Enrollment: 110 subjects
Study Type: Observational
Study Design:
- Observational Model: Case Control
Conditions:
Interventions:
Eligibility
Inclusion Criteria:
Girls and boys ages 8 to 18 years old
Non-obese cohort: body mass index less than 75th percentile for age
Obese cohort: body mass index more than 95th percentile for age
Exclusion Criteria:
Underlying medical problem with potential to affect growth, pubertal development or glucose homeostasis
Chronic medical therapy with glucocorticoids, growth hormone, estrogen, progesterone, testosterone, or other medications with the potential to alter growth, pubertal development or glucose homeostasis within the proceeding 6 months
Personal history of diabetes
Family history of diabetes in first degree relative
Inability to have MRI scan performed due to metal prosthesis or implant
- Gender
Both
- Mininum Age
8 Years
- Maximum Age
18 Years
- Healthy Volunteers
Accepts Healthy Volunteers
Resources
Source: Massachusetts General Hospital
Authority: United States: Institutional Review Board
Locations
-
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Officials
Amy D Fleischman, MD, MMSc (Principal Investigator, Massachusetts General Hospital)
Sponsors
Massachusetts General Hospital (Lead Sponsor)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Collaborator)
Lawson Wilkins Pediatric Endocrine Society (Collaborator)
Children's Hospital Boston (Collaborator)
References
None.
Links
None.
- Date Verified
- September 1st, 2010
- First Received
- September 29th, 2010
- Last Changed
- September 29th, 2010
Information obtained from ClinicalTrials.gov on June 09, 2011. Link to the current ClinicalTrials.gov record.
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