Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth

Inclusion Criteria:

• Lean (not overweight or obese) will be defined as a body mass index (BMI) (kg/m2) lessthan the 85th percentile specific for age and gender, overweight will be defined as aBMI between the 85th and 95th percentiles, and obesity will be defined as a BMIgreater than the 95th percentile1. Following the oral glucose tolerance test (OGTT, 75gm) (HIC #11190), children will be classified as normal glucose tolerant if plasmaglucose at two hours is <140 mg/dl and as impaired glucose tolerant if plasma glucoseis ≥140 mg/dl. To enter the study all children and adults must be in good generalhealth, 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 andphysical examination prior to enrollment in the study. Tanner stage of pubic breastand gonadal development will be determined by physical examination and by measurementsof estradiol, testosterone and IGF1 as biochemical markers of pubertal development.

Exclusion Criteria:

• Medications that are known to alter glucose or insulin metabolism, such as oralsteroids, 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 alatex allergy. Lean subjects must have at least one parent, grandparent or siblingwith 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 obtainedvia finger stick in parents of potential volunteers in whom status of diabetes or IFGis unknown. Exclusion criteria also include known diabetes or taking any medicationthat alters liver function and blood pressure. Youth on chronic anti-inflammatorymedications or who consume alcohol are also excluded.