Cardiometabolic Risk and Obesity in Adolescents With Down Syndrome
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Down Syndrome
- Sponsor
- Children's Hospital of Philadelphia
- Enrollment
- 257
- Locations
- 2
- Primary Endpoint
- Non-HDL Cholesterol
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this research study is to determine which measures best capture cardiovascular disease (CVD) risk and type 2 diabetes (T2DM) risk in children and adolescents with Down syndrome (DS).
We hypothesize that DS is associated with worse cardiometabolic risk factors for a given body mass index compared to controls. This difference arises at least in part, from increased fat tissue.
Detailed Description
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Non-HDL Cholesterol
Time Frame: Study Visit 1
Non-HDL cholesterol measured via fasting blood draw
Lipid Subparticles
Time Frame: Study Visit 1
Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
Body Mass Measures
Time Frame: Study Visit 1
Adiposity measured by Dual-energy X-ray absorptiometry
Insulin Resistance
Time Frame: Study Visit 1
Insulin Resistance (HOMA-IR) was calculated as \[fasting insulin (uIU/mL) x fasting glycemia (mmol/L)\]/22.5
Cardiometabolic Risk Biomarker Proteins
Time Frame: Study Visit 1
hs-CRP, PAI-1, and IL-6 run on samples from fasting blood drawn Study Visit 1.
Abnormal Glucose Tolerance
Time Frame: Study Visit 1
Impaired fasting glucose (IFG) was defined as fasting glucose ≥ 100 mg/dl. Impaired glucose tolerance (IGT) was defined as 2-hour glucose 140-199 mg/dl measured as part of an oral glucose tolerance test.
Visceral Fat
Time Frame: Study Visit 1
Adiposity measured by Dual-energy X-ray absorptiometry
Left Ventricular Mass
Time Frame: Study Visit 1
Cardiac end organ injury assessed by echocardiography. Left Ventricular Mass (LVM) was measured by area/length method using the apical four-chamber and parasternal short-axis views. LVM was calculated as LV area × LV length × 1.05 × 5/6.
Pulse Wave Velocity
Time Frame: Study Visit 1
Cardiac end organ injury assessed by Pulse Wave Velocity (PWV)
Lipid Subparticles (Size)
Time Frame: Study Visit 1
Lipoprotein subclass particle analysis run on samples from fasting blood drawn Study Visit 1.
Secondary Outcomes
- Health Related Quality of Life - PedsQL(Study Visit 1)
- Health Related Quality of Life - IWQOL(Study Visit 1)