Down Syndrome Metabolic Health Study

DS affects 1 per 800 births and is one of the most common causes of developmental disability
in the US. Life expectancy for Down syndrome has increased significantly: estimated median
survival in the US in 1997 was 49 years. DS is associated with an increased risk for obesity,
with an estimated prevalence of 47-48% in adults and 30-50% in children with DS. Adolescents
with DS are more likely to have increased adiposity compared to unaffected peers and may be
at increased risk for obesity-related co-morbidities, such as type 2 diabetes and
cardiovascular disease. How one defines obesity in DS is not clear. Individuals with DS have
short stature and possibly increased adiposity, and the body mass index (BMI) used to define
obesity for otherwise healthy populations may not accurately depict body fatness or capture
cardiometabolic risk in DS.

Congenital heart disease (CHD) affects approximately 50% of individuals with DS; the National
Institutes of Health Heart Lung and Blood Institute (NHLBI) Working Group on Obesity and
Other Cardiovascular Risk Factors in Congenital Heart Disease highlighted the high prevalence
of obesity in the setting of CHD, and called for studies to identify obesity measures that
are more sensitive than BMI as well as studies of CVD risk prevention. Unfortunately,
clinicians caring for obese adolescents with DS with or without CHD have little scientific
evidence upon which to base guidance regarding cardiometabolic risk (CMR): data regarding CVD
risk and prevalence of pre-diabetes and T2DM in obese adolescents with DS are lacking.

The measure of body fatness which best predicts CMR in DS is not known. We plan to compare
BMI and other measures of body fatness in healthy controls and adolescents with DS to
determine which measures best capture CVD and/or T2DM risk. These data will equip medical
providers with the tools to better assess risk, initiate prevention measures, and guide
screening in adolescents with DS.

Inclusion Criteria:

- Both groups: Ages 10 - 20

- Both groups: Parental/guardian permission (informed consent) and if appropriate, child
assent.

- Down syndrome group only: diagnosis of Down syndrome

Exclusion Criteria (both groups):

- Major organ system illness (such as leukemia), except for type 2 Diabetes

- Cyanotic congenital heart disease and/or pulmonary hypertension

- Medically unstable congenital heart disease

- Pregnancy

- Genetic syndrome known to affect glucose tolerance

- Familial hypercholesterolemia

- Currently treated with medications known to affect insulin sensitivity (other than
diabetes agents in participants with type 2 diabetes)