Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth

Condition(s) targeted: Obesity; Impaired Glucose Tolerance; Type 2 Diabetes Mellitus

Intervention: Rosiglitazone (Drug); Placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Yale University

Official(s) and/or principal investigator(s):
Sonia Caprio, MD, Principal Investigator, Affiliation: Yale School of Medicine Department of Pediatric Endocrinology

Overall contact:
Sonia Caprio, MD, Phone: 203-785-5692, Email: sonia.caprio@yale.edu

The purpose of the study is to determine whether treatment of children and adolescents with Impaired Glucose Tolerance (IGT) with rosiglitazone will lead to improvements in insulin sensitivity and glucose tolerance.

Official title: Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Improvements in insulin sensitivity and glucose tolerance.

Decrease in the visceral-to-subcutaneous abdominal fat ratio, intrahepatic fat, and intramyocellular lipid content.

Secondary outcome:

Restoration of normal ability of the beta cell to sense and respond to incremental changes in glucose levels.

Reduced lipolysis as reflected by a reduced glycerol turnover.

Increased adiponectin levels and decreased inflammatory cytokines.

Decreased cardiovascular risk factors.

Reduction in size but an increase in the number of adipocytes in the subcutaneous fat depot.

A change in the expression of genes that are known to be linked to insulin resistance and that are affected by rosiglitazone.

Detailed description: Impaired Glucose Tolerance (IGT) is a prelude to diabetes, which is increasing in prevalence in obese children and adolescents with marked obesity. This condition tends to progress to Type 2 Diabetes Mellitus (T2DM) at an alarmingly rapid tempo. The increased prevalence of childhood and adolescent obesity and greater risk of IGT, and progression to diabetes, in this population set the stage for a series of studies aimed at understanding the metabolic phenotype and natural history of pre-diabetes in obese youth. We found that obese children and adolescents with IGT are characterized by marked insulin resistance related to altered lipid partitioning, favoring lipid deposition in the visceral and intramyocellular compartment. Furthermore, we found an impairment of the acute insulin response in these youngsters. Follow-up revealed a rapid deterioration from IGT to frank diabetes. Based on these studies, there is a strong rationale for changing the balance between visceral and subcutaneous fat and muscle lipid content in a more favorable pattern in order to improve insulin sensitivity.

The primary objective of this study is to determine, in a group of ethnically diverse children and adolescents with IGT, whether treatment with rosiglitazone leads to improvements in insulin sensitivity and glucose tolerance. Secondary objectives are to determine whether rosiglitazone is safe and well tolerated.

Minimum age: 10 Years. Maximum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Good general health

- Aged 10 to 18 yrs (females: Tanner stage II-V;and males: testes size>6ml)

- IGT based on 2-hr plasma glucose>140mg/dl and <200mg/dl during an OGTT.

Exclusion Criteria:

- Baseline creatinine>1. 0mg

- AST and ALT>2. 5 ULN

- Anemia (Hct<30)

- Pregnancy (females must have a negative urine pregnancy test during the study)

- Cardiac or pulmonary or other significant chronic illness

- Plans to increase the frequency or intensity of a regular exercise program

- Psychiatric disorder or substance abuse of anorexic agents.

Sonia Caprio, MD, Phone: 203-785-5692, Email: sonia.caprio@yale.edu

Yale School of Medicine, New Haven, Connecticut 06520, United States; Recruiting
Sonia Caprio, MD, Phone: 203-785-5692, Email: sonia.caprio@yale.edu
Sonia Caprio, MD, Principal Investigator

Starting date: November 2005
Ending date: December 2008
Last updated: June 16, 2008