Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth
Condition: Impaired Glucose Tolerance; Pre-diabetes; Childhood Obesity; Insulin Resistance; Metabolic Syndrome
MeSH terms: Diabetes Mellitus; Metabolic Syndrome; Insulin Resistance; Pediatric Obesity; Prediabetic State; Glucose Intolerance
Study type: Observational

Summary: 
      The purpose of the study is to determine the role of beta-cell function and insulin
      resistance in the development of impaired glucose tolerance (IGT) and type 2 diabetes in
      children and adolescents who have an increased risk of developing type 2 diabetes due to
      overweight/obesity or a family history of overweight/obesity, diabetes and/or impaired
      fasting glucose. It is hypothesized that: 1)Obese adolescents with IGT will be more insulin
      resistant than obese adolescents with NGT. Insulin resistance will be the best predictor of
      changes in glucose tolerance status., 2)Beta cell function will be impaired in obese
      adolescents with IGT compared to obese adolescents with NGT., 3)Obese adolescents with IGT
      will present with greater intramyocellular, intrahepatic and visceral fat than obese
      adolescents with NGT. Furthermore, obese adolescents with IGT will have larger adipocytes,
      while having significantly fewer adipocytes compared to obese adolescents with NGT. Obese
      adolescents with IGT will also have altered expression of key genes related to insulin
      resistance., and 4)Abnormalities in endothelial function as manifested by low FMD and PAT are
      already present in obese adolescents with IGT and are linked to insulin resistance.
    

Detailed description: 
      Type 2 diabetes is a serious and common chronic disease affecting an estimated 6.6% of the
      U.S. population 20 to 74 years of age. Among children, type 2 diabetes has previously been
      reported to account for 2% to 3% of all patients with diabetes mellitus. Recent studies,
      however, indicate that the prevalence of this disorder is increasing in the pediatric
      population. This phenomenon parallels the increased prevalence of obesity in children and
      adolescents, particularly in African-American and Hispanic ethnic groups. Despite the wealth
      of knowledge concerning the epidemiology, pathophysiology and treatment of type 2 diabetes in
      adults, we know little about the disease in children.Paralleling the rise in childhood
      obesity and type 2 diabetes is an increase in the metabolic syndrome in youth. The metabolic
      syndrome, also known as "Syndrome X," is characterized by hypertension, type 2 diabetes,
      dyslipidemia and obesity. This syndrome was first described in 1966 by Camus and again by
      Reaven in 1988. Cook et al. showed that the metabolic syndrome is already present in 6.8% of
      12-19 year-olds with a BMI between the 85th and 95th percentiles, and in 28.7% of those with
      a BMI greater than the 95th percentile. In addition, recent studies from our group suggest
      that risk factors for type 2 diabetes and the metabolic syndrome are already present in
      overweight children and adolescents. As the degree of obesity worsens, the prevalence of
      these risk factors greatly increase.Overweight and obese adolescents with NGT and with IGT
      will be recruited. Progression from NGT to IGT and from IGT to type 2 diabetes will be
      assessed by annual oral glucose tolerance tests (OGTT). Comprehensive metabolic assessments
      will be employed to examine within and between group differences in insulin action and
      beta-cell function at baseline and during the follow-up.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children and Adolscents seen at the Yale Pediatric Obesity Clinic.
      
Keywords: Pre-Diabetes; Childhood Obesity; Metabolic Syndrome; insulin resistance; Impaired Glucose Tolerance; Non Alcoholic Fatty Liver Disease; High Molecular Weight Adiponectin; Hypoadiponectinemia