Endothelial Function in Obese Adolescents



Status:Completed
Conditions:Obesity Weight Loss, Peripheral Vascular Disease, Cardiology, Endocrine
Therapuetic Areas:Cardiology / Vascular Diseases, Endocrinology
Healthy:No
Age Range:12 - 18
Updated:1/23/2019
Start Date:March 2011
End Date:January 2014

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Effect Of Obesity And Hyperglycemia on Endothelial Function in Inner City Bronx Adolescents

Childhood obesity is perhaps the most significant public health problem in the most developed
countries and is rapidly becoming so in developing countries. National Health and Nutrition
Examination Survey data shows a 3-fold increase in the prevalence of obesity in childhood,
over past few decades. Furthermore, childhood obesity has markedly contributed to the
prevalence of the metabolic syndrome and type 2 diabetes in U.S. children. Alarmingly, there
is increasing evidence that atherosclerosis develops silently during childhood in obese
children. In the Bogalusa Heart Study, pediatric autopsy studies showed a clear relationship
between the number and severity of risk factors, principally obesity, with atherosclerosis in
both the aorta and coronary arteries. Increased intimal medial thickness (IMT) was not
present among obese adults who had been normal weight as children, emphasizing the cumulative
effects of childhood obesity persisting into adulthood. Thus, the need for primary prevention
of cardiovascular disease beginning in childhood is strongly suggested.

Following informed consent, a detailed history and physical examination will be performed
including supine blood pressure taken twice after a 20 minute period of rest, height (using
Harpenden stadiometer) to the nearest 0.1 cm and weight will be measured to the nearest 0.1
kg with a balance scale, pubertal staging using the method of Marshall and Tanner, waist
measurement obtained at the minimal circumference of the abdomen, hip measurements with a
plastic tape while the subject is standing and recorded at the widest diameter over the
greater trochanters. BMI (kg/m2) and waist to hip ratio will be calculated. Screening labs in
all recruited subjects: A fasting laboratory evaluation will include chemistry panel (basic
metabolic, liver function tests), Complete Blood Count (CBC), lipid profile, urinalysis and
HbA1c. All obese recruited subjects after a 12 hour fast will undergo an OGTT using a glucose
load of 1.75 g/kg body weight with a maximum of 75 g. Blood samples will be collected for
insulin, glucose, leptin, adiponectin, High sensitive C-reactive protein (hsCRP) and Free
Fatty Acids (FFA). Serum and urine will be stored at -70 (degree Centigrade)C for measuring
markers of oxidative stress and adipocytokines (including Tumor Necrosis Factor (TNF)-α,
Plasminogen Acivator Inhibitor (PAI)-1) for future studies depending on the funding
availability.

Subjects who fulfill the study criteria would be admitted to Clinical Research Center to
evaluate endothelial function by RH-PAT.

RH-PAT for endothelial function Reactive hyperemia peripheral arterial tonometry (RH-PAT) is
a noninvasive technique used to assess peripheral microvascular endothelial function by
measuring changes in digital pulse volume during reactive hyperemia (Bonetti, Kuvin). Pulse
volume is measured by a finger plethysmographic device that allows isolated detection of
pulsatile arterial volume changes, which are sensed by a pressure transducer and transferred
to a computer where the signal is amplified, displayed and stored (EndoPAT, Itamar Medical).
Studies are performed with the patient at rest, in a comfortable, thermo neutral environment.
Fingertip probes are placed on the index finger of both hands and 5 minutes of baseline
recording are obtained. Blood flow is then occluded in one arm for 5 minutes, using a
standard blood pressure cuff. Recording continues in both fingers during occlusion and for 5
minutes after release of the cuff. The RH-PAT index is calculated as the ratio of the average
pulse amplitude in the post-hyperemic phase divided by the average baseline amplitude, with
normalization to the signal in the control arm to compensate for any systemic changes.

Inclusion Criteria:

- Children in the age range of 12-18 years

- For the lean group, age and sex matched subjects with BMI between 5th-85th percentiles

- Obese group defined as BMI ≥95th percentile. These will further be subgrouped into
those with normal and those with abnormal glucose tolerance normal glucose tolerance
(NGT) defined as fasting glucose level<100mg/dl and a 2 hour postprandial glucose
level<140mg/d and abnormal OGTT defined as fasting level ≥100mg/dl and/or 2hr ≥140
using a glucose load of 1.75 g/kg body weight (max 75 g).Hence, we will

Exclusion Criteria:
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