Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth

This study is currently recruiting participants.
Verified July 2013 by Yale University
Sponsor:
Information provided by (Responsible Party):
Sonia Caprio, Yale University
ClinicalTrials.gov Identifier:
NCT00536250
First received: September 25, 2007
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition
Impaired Glucose Tolerance
Pre-diabetes
Childhood Obesity
Insulin Resistance
Metabolic Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • glucose tolerance [ Time Frame: baseline and follow up ] [ Designated as safety issue: No ]
    glucose tolerance status as determined by oral glucose tolerance test - fasting and 2 hour glucoses

  • insulin resistance [ Time Frame: baseline and follow up ] [ Designated as safety issue: No ]
    insulin resistance as measured during oral glucose tolerance test by WBISI

  • hepatic fat content and abdominal fat ratio [ Time Frame: baseline and follow up ] [ Designated as safety issue: No ]
    hepatic fat content and abdominal fat ratio measured by liver mri and abdominal mri


Estimated Enrollment: 255
Study Start Date: September 2001
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   8 Years to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Children and Adolscents seen at the Yale Pediatric Obesity Clinic.

Criteria

Inclusion Criteria:

  • Lean (not overweight or obese) will be defined as a body mass index (BMI) (kg/m2) less than the 85th percentile specific for age and gender, overweight will be defined as a BMI between the 85th and 95th percentiles, and obesity will be defined as a BMI greater than the 95th percentile1. Following the oral glucose tolerance test (OGTT, 75 gm) (HIC #11190), children will be classified as normal glucose tolerant if plasma glucose at two hours is <140 mg/dl and as impaired glucose tolerant if plasma glucose is ≥140 mg/dl. To enter the study all children and adults must be in good general health, have a normal medical history and physical exam, and have no endocrinopathies (normal thyroid function test) or other diseases that might affect glucose metabolism.
  • Eligibility will be determined by a comprehensive family and medical history and physical examination prior to enrollment in the study. Tanner stage of pubic breast and gonadal development will be determined by physical examination and by measurements of estradiol, testosterone and IGF1 as biochemical markers of pubertal development.

Exclusion Criteria:

  • Medications that are known to alter glucose or insulin metabolism, such as oral steroids, or certain psychiatric medications, such as Celexa, Lithium and Paxil. Children and adults will be excluded from participating in the PAT test if they have a latex allergy. Lean subjects must have at least one parent, grandparent or sibling with overweight/obesity (BMI >25), type 2 diabetes, and/or impaired fasting glucose (IFG) (fasting glucose >100 mg/dl). A fasting plasma glucose level will be obtained via finger stick in parents of potential volunteers in whom status of diabetes or IFG is unknown. Exclusion criteria also include known diabetes or taking any medication that alters liver function and blood pressure. Youth on chronic anti-inflammatory medications or who consume alcohol are also excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00536250

Contacts
Contact: Sonia Caprio, M.D. (203)785-5692 sonia.caprio@yale.edu
Contact: Bridget Pierpont, M.A. (203)785-2942 bridget.pierpont@yale.edu

Locations
United States, Connecticut
47 College Street Recruiting
New Haven, Connecticut, United States, 06520
Principal Investigator: Sonia Caprio, M.D.         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Sonia Caprio, M.D. Yale University
  More Information

No publications provided by Yale University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sonia Caprio, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00536250     History of Changes
Other Study ID Numbers: 0102012241, R01 HD40787
Study First Received: September 25, 2007
Last Updated: July 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Pre-Diabetes
Childhood Obesity
Metabolic Syndrome
insulin resistance
Impaired Glucose Tolerance
Non Alcoholic Fatty Liver Disease
High Molecular Weight Adiponectin
Hypoadiponectinemia

Additional relevant MeSH terms:
Insulin Resistance
Metabolic Syndrome X
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Glucose Intolerance
Prediabetic State
Endocrine System Diseases
Hyperinsulinism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia

ClinicalTrials.gov processed this record on April 17, 2014