Endothelial Function in Obese Adolescents
Condition: Insulin Resistance; Glucose Intolerance; Obesity; Atherosclerosis
MeSH terms: Atherosclerosis; Obesity; Insulin Resistance; Glucose Intolerance
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Reactive hyperemia peripheral artery tonometry (Rh-PAT); Blood levels for glucose, insulin, lipids and adipocytokines
Intervention type(s): Other; Other
Intervention description(s): Pulse volume is measured by a finger plethysmographic device which are sensed by a pressure transducer and transferred to a computer where the signal is amplified, displayed and stored (EndoPAT, Itamar Medical). 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.; A fasting laboratory evaluation will include chemistry panel (basic metabolic, liver function tests), 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, hsCRP and FFA. Serum and urine will be stored at -70 degrees Centigrade for measuring markers of oxidative stress and adipocytokines (including TNF-α, PAI-1)
Other intervention name(s): Endopat
Intervention MeSH terms: Insulin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Obesity; endothelial function; Rh-PAT; adipocytokines