Mitochondrial Function in Pediatric Obesity

NCT00577174 | Unknown

• 3 other identifiers: 1K23DK0806582006p001067, Partners IRB575, MIT IRB
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Obesity; Insulin Resistance

Keywords

Children; Obesity; Insulin resistance; Diabetes; Mitochondrial Function

Outcome Measures

Primary Outcomes (2)

• Determine whether children with pediatric obesity have impaired mitochondrial function based on 31P magnetic resonance spectroscopy when compared to healthy non-obese control children

  4 years

• Examine the relationship between mitochondrial function and insulin resistance in obese and non-obese children

  four years

Secondary Outcomes (2)

• Determine the impact of pubertal stage, dietary intake, activity recall, inflammatory markers and metabolic markers on mitochondrial function in obese and non-obese children

  four years

• 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

  four years

Study Arms (2)

1. Controls

Healthy children ages 8 to 18 years

2. Obese childrens

Obese children, ages 8 to 18 years

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy and obese children from clinical practices and the local community

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Lawson Wilkins Pediatric Endocrine Society: collaborator
• Boston Children's Hospital: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• Fleischman A, Kron M, Systrom DM, Hrovat M, Grinspoon SK. Mitochondrial function and insulin resistance in overweight and normal-weight children. J Clin Endocrinol Metab. 2009 Dec;94(12):4923-30. doi: 10.1210/jc.2009-1590. Epub 2009 Oct 21.

  PMID: 19846731 RESULT

• Fleischman A, Makimura H, Stanley TL, McCarthy MA, Kron M, Sun N, Chuzi S, Hrovat MI, Systrom DM, Grinspoon SK. Skeletal muscle phosphocreatine recovery after submaximal exercise in children and young and middle-aged adults. J Clin Endocrinol Metab. 2010 Sep;95(9):E69-74. doi: 10.1210/jc.2010-0527. Epub 2010 Jun 16.

  PMID: 20554709 RESULT

• McCormack SE, McCarthy MA, Farilla L, Hrovat MI, Systrom DM, Grinspoon SK, Fleischman A. Skeletal muscle mitochondrial function is associated with longitudinal growth velocity in children and adolescents. J Clin Endocrinol Metab. 2011 Oct;96(10):E1612-8. doi: 10.1210/jc.2011-1218. Epub 2011 Aug 10.

  PMID: 21832105 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, white blood cells

MeSH Terms

Conditions

Obesity; Insulin Resistance; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Study Officials

• Amy D Fleischman, MD, MMSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 18, 2007
• First Posted: December 20, 2007
• Study Start: June 1, 2007
• Primary Completion: August 1, 2011
• Study Completion: October 1, 2012
• Last Updated: April 30, 2012

Record last verified: 2012-04

Locations

US (1)