Please select the eligibility criteria that correspond to the clinical trial below.
Title: Understanding the Effects of Therapeutic Intervention on Cardiovascular Risk Markers, Insulin Resistance, and Intra-Hepatic Fat Contents in Obese Children at High Risk for the Metabolic Syndrome.
Brief Summary: In Protocol #2, we will select 30 obese pubertal and 30 obese prepubertal subjects with an abnormal cytokine profile (i.e. fibrinogen and/or hsCRP concentration greater than or equal to 2 Standard Deviations (SD) above the mean established in our lab for lean controls in Protocol #1). They will be randomly assigned to either lifestyle intervention (diet/exercise) or diet/exercise plus metformin for 6 months. After the 6 month evaluation the subjects will cross over the treatment arms, i.e., those that were doing diet/exercise intervention only will add metformin, those that were doing the diet/exercise plus metformin will discontinue the metformin and continue with diet/exercise changes only. Intrahepatic fat contents will be measured as well.

The investigators hypothesize that obese children in these age groups will have increased cardiovascular risk related to their obese state before reaching the currently defined criteria of metabolic syndrome.

The investigators hypothesize that these cardiovascular risks can be reduced with lifestyle and drug interventions.


Options:
A: Inclusion Criteria:

* Previously enrolled in, complied with, and completed the INQ/K/003411 (Glucosanol weight loss) study, with weight loss of at least 3% of baseline body weight
* Age 18 to 60 years at the time of inclusion into the INQ/K/003411 study
* BMI between 25-35 at the time of inclusion into the INQ/K/003411 study
* Expressed desire for weight maintenance
* Accustomed to 3 main meals per day
* Commitment to avoid the use of other weight loss products during study
* Females' agreement to use appropriate birth control methods during the active study period
* Subject declares in writing his/her consent to participate, understands requirements of the study and is willing to comply

Exclusion Criteria:

* Known sensitivity to the ingredients of the device (Phaseolus vulgaris or members of the Fabaceae family)
* History of diabetes mellitus • Fasting blood glucose more than 7 mmol/L
* History or clinical signs of endocrine disorders which may influence body weight (e.g. Cushing's disease, thyroid gland disorders)
* Clinically relevant excursions of safety parameter
* Current use of anti-depressants
* Presence of acute or chronic gastrointestinal disease (e.g. IBD, coeliac disease, pancreatitis)
* Uncontrolled hypertension (more than 160/110 mm Hg)
* Stenosis in the GI tract
* Bariatric surgery
* Abdominal surgery within the last 6 months prior to enrollment
* History of eating disorders like bulimia, anorexia nervosa within the past 12 months
* Other serious organ or systemic diseases such as cancer
* Any medication that could influence GI functions such as antibiotics, laxatives, opioids, glucocorticoids, anticholinergics, or anti-diarrheals
* Pregnancy or nursing
* Any medication or use of products for the treatment of obesity (e.g. Orlistat, other fatbinder, carb/starch blocker, fatburner, satiety products etc.)
* More than 3 hours strenuous sport activity per week
* History of abuse of drugs, alcohol or medication
* Smoking cessation within 6 months prior to enrolment
* Inability to comply due to language difficulties
* Presence of other factor(s) that, in the investigator's judgement, should preclude subject participation
B: Inclusion Criteria (during Screening and Run-in period):

* Diabetes by ADA criteria (laboratory determinations of fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL) documented and confirmed in medical record. For patients diagnosed with diabetes during screening who have a normal fasting glucose but an elevated two-hour glucose during an OGTT, the HbA1c must be ≥ 6%.
* Duration since diagnosis less than two years by date of randomization.
* BMI ≥ 85th percentile documented at time of diagnosis or at screening.
* Fasting C-peptide at screening (drawn at least one week after treatment for ketosis or acidosis, if applicable) \> 0.6 ng/mL.
* Absence of pancreatic autoimmunity (both GAD and ICA512 negative).
* Age 10-17, with randomization prior to 18th birthday.
* Signed informed consent/assent forms for the pre-randomization period.
* A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
* Fluency in English or Spanish for both child and family member.
* Patient and family able to fully participate in trial protocol in the opinion of the investigator.

Exclusion Criteria (during Screening and Run-in period):

* Participating in another interventional research study protocol in the past 30 days.
* Genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
* Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
* Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
* Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
* Patient on medication(s) that are known to cause weight gain within the last 30 days.
* Patient on any weight-loss medication(s) within the last 30 days.
* Patient on medication(s) known to affect the metabolism of study drug.
* Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member.
* Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
* Calculated creatinine clearance \< 70 mL/min.
* Any transaminase \> 2.5 ULN. If any transaminase 1.5-2.5 times ULN, then patient must be appropriately evaluated by PCP (minimum evaluation includes ceruloplasmin level, alpha-1 antitrypsin phenotype, ANA, anti-smooth muscle antibody, anti-LKM antibody, anti-HCV, and anti-HBc total antibody not IgM, iron, and TIBC) and is eligible if all other causes for elevation are ruled out and it is presumed due only to non-alcoholic fatty liver disease (NAFLD).
* Diabetic ketoacidosis (DKA) at any time after diagnosis unless only a single episode of DKA related to a significant medical illness.
* Physical limitations preventing patient from being randomized to the lifestyle intervention.
* Patient plans to leave the geographic area within one calendar year.
* Abnormal reticulocyte count or HbA1c chromatogram at time of screening.
* Admitted use of anabolic steroids within the past 60 days.
* Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
* Patient participates in a formal weight-loss program.

Inclusion Criteria (post Run-in and Randomization):

* Duration since diagnosis less than 2 years at randomization.
* HbA1c \< 8% on metformin alone.
* Age 10-17, with randomization before patient is 18 years old.
* Signed consent/assent forms for randomization and the post-randomization phase.
* A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
* Fluency in English or Spanish for both child and family member.
* Patient and family able to fully participate in trial protocol in the opinion of the investigator.

Exclusion Criteria (post Run-in and Randomization):

* Refractory hypertension: average systolic blood pressure ≥ 150 mmHg or average diastolic blood pressure ≥ 95 mmHg despite appropriate medical therapy.
* Refractory hyperlipidemia: total cholesterol \> 300 mg/dL or LDL \> 190 mg/dL or triglycerides \> 800 mg/dL, despite appropriate medical therapy.
* Refractory anemia: hematocrit \< 30% or hemoglobin \< 10 gm/dL despite appropriate medical therapy.
* Patient on a thiazolidinedione (TZD) within the last 12 weeks.
* Patient on non-study diabetes medications within the past 6 weeks.
* Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
* Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
* Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
* Patient on medication(s) that are known to cause weight gain within the last 30 days.
* Patient on any weight-loss medication(s) within the last 30 days.
* Patient on medication(s) known to affect the metabolism of study drug.
* Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member, assessed by mastery of standard diabetes education program administered during run-in.
* Inability to comply with requirements of study during run-in period.
* Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
* Calculated creatinine clearance \< 70 mL/min.
* Physical limitations preventing patient from being randomized to the lifestyle intervention.
* Patient plans to leave the geographic area within one calendar year.
* Admitted use of anabolic steroids within 60 days.
* Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
* Patient participates in a formal weight loss program.
* Episode of DKA during the run-in.30.
* Edema at the time of randomization (a participant who experiences edema during run-in must have recovered within 2 weeks and be edema free for 1 week prior to randomization).
C: Inclusion Criteria:

* Subject's body mass index (BMI) was \>= 27 kg/m(2) and \<= 45 kg/m(2) or their BMI was \>= 25 kg/m(2) and \< 27 kg/m(2) with waist circumference of \>= 102 cm in males or \>= 88 cm in females.
* Medical history positive for:

  * Preexisting cardiovascular disease (i.e., coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease) and/or
  * Type 2 diabetes mellitus with at least 1 other risk factor (i.e., dyslipidemia, controlled hypertension, current smoker, or diabetic nephropathy with evidence of microalbuminuria)

Exclusion Criteria:

* History of recent myocardial infarction.
* Heart failure symptoms greater than New York Heart Association Functional Class II.
* Hemodynamically significant valvular or left ventricular (LV) tract obstruction.
* Subjects without a pacemaker and with any of the following:

  * Sinus bradycardia (\< 50 bpm)
  * Sick sinus syndrome
  * Atrioventricular block of more than 1st degree
* Mean sitting systolic blood pressure (SBP) \> 160 mmHg. Mean sitting diastolic blood pressure (DBP) \> 100 mmHg. Mean sitting heart rate (HR) \> 100 bpm.
* Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias.
* Planned cardiac surgery or coronary angioplasty within 6 months of screening.
* History of recent non-hemorrhagic stroke or transient ischemic attack (TIA), history of hemorrhagic stroke.
* Hyperthyroidism.
* Known chronic liver disease or endstage renal disease.
* Severe, symptomatic benign prostatic hyperplasia which may require surgery.
* Known pheochromocytoma, history of narrow angle glaucoma, Gilles de la Tourette syndrome, history of seizures, history of bariatric or abdominal obesity surgery (excluding liposuction).
* Concomitant use of monoamine oxidase inhibitors or drugs that increase levels of serotonin in the brain.
* Treated hypertension stabilized for less than 3 months.
* Inability to perform regular physical activity.
D: Inclusion Criteria:

* Ages 7-18 years.
* Greater than the 95th percentile body mass index for their age and gender.
* Children are in Tanner Stage I or IV or V.
* Normal Blood Pressure.
* Normal fasting glucose.
* Normal lipids.
* Menstruating girls must have completed their most recent period at least 2 weeks prior to blood draw.
* No recent illness, no chronic illnesses, no routine medications, no smoking or alcohol intake.
* Must pass the screening test done in Protocol #1.
* Must have higher values than normal for certain blood tests related to heart disease that were measured in Protocol #1.

Exclusion Criteria:

* Chronic active illnesses.
* Recent illnesses.
* Use of routine medications, vitamins, herbal remedies, oral contraceptive pills, or other over the counter medications within 4 weeks of blood draw.
* History of recent or chronic smoking.
* Currently pregnant.
* Impaired fasting glucose.
* Dyslipidemia.
* Actively in puberty.
* Weight greater than 300 pounds.
* Metal in the abdomen.
* History of being overweight greater than 5 years.

Answer: D