Study of Post-Meal Blood Sugar Peaks in Association With Vascular Disease in Childhood Obesity

Obese subjects (BMI > 97%tile for age and sex) with a family history of T2DM and clinical
signs of insulin resistance such as acanthosis nigricans will be invited to partake in this
study.

Obese subjects will have a baseline oral glucose tolerance test (OGTT), screening labs
(liver/kidney functions, lipid profile, thyroid function tests, CBC, metabolic and
cardiovascular laboratory parameters -- such as inflammatory cytokines and pro-thrombotic
factors), wear a Continuous Glucose Monitoring System (CGMS) for 3-days on 2 occasions
(baseline, post-intervention), have a standardized snack once during each CGMS session,
collect urine samples for microalbumin and have vascular tests (PAT and FMD) done at
baseline and post intervention.

Subjects assigned to treatment will undergo a 6-7 week intervention with acarbose.

Lean Control Subjects:

As for obese subjects, lean subjects will be asked to bring in first morning voids for
testing of microalbuminuria. They will also have endothelial function tests (PAT and FMD) as
well as CGMS placement. A set of screening labs will also be drawn (fasting glucose,
insulin, thyroid function and lipid profile will be drawn). Furthermore blood will be
collected for analysis of novel cardiovascular parameters (such as inflammatory cytokines
and pro-thrombotic factors). However lean subjects will not have an OGTT done and will not
be offered drug intervention. The endothelial function testing in the lean controls will
serve as control data for the vascular function testing in the obese children. Similar to
obese subjects, lean subjects will be instructed to take a standardized snack in the
afternoon prior to returning for CGMS removal.

Obese Subjects:

Inclusion Criteria:

- Obesity (BMI > 97%tile for age and sex matched normative data)

- Good general health, taking no medication on a chronic basis

- Age 12-19 yrs, in puberty (girls: breast: Tanner stage II to V, boys: testicular
volume >6ml)

- Girls who are sexually active must use adequate birth control methods(such as barrier
method or oral contraception) and must have a negative pregnancy test

- Normal liver function tests

Exclusion Criteria:

- Raynaud's syndrome

- Pregnancy or breastfeeding mothers

- Smokers

- Anemia (Hct < 35)

- Baseline creatinine > 1.0 mg

- Abnormal liver transaminases > 1.5X the upper limit of normal

- Presence of endocrinopathies (Cushing syndrome, hypothyroidism)

- Presence or history of gastrointestinal disorders (Inflammatory bowl disease,
irritable bowl disease, hernia, ileus)

- Presence of significant chronic illness of any kind

- Drug therapy (examples of commonly occurring drug therapy include any drugs to treat
asthma, hypertension, dyslipidemia, insulin resistance, depression)

- Psychiatric disorders

- History of substance abuse (including anorexic agents)

Control Subjects:

Inclusion Criteria:

- Lean (BMI < 85%tile for age and sex matched normative data)

- Good general health, taking no medication on a chronic basis

- Age 12-25 yrs, in puberty (girls: breast: Tanner stage II to V, boys: testicular
volume >6ml)

- Girls who are sexually active must use adequate birth control methods (such as
barrier method or oral contraception) and must have a negative pregnancy test

Exclusion Criteria:

- Raynaud's syndrome

- Pregnancy or breastfeeding mothers

- Smokers

- Presence of endocrinopathies (Cushing syndrome, hypothyroidism Presence of
significant chronic illness of any kind

- Drug therapy (examples of commonly occurring drug therapy include any drugs to treat
asthma, dyslipidemia, hypertension, depression)

- Psychiatric disorders

- History of substance abuse

- First degree relative with either T1DM or T2DM

- Presence of acanthosis nigricans