Effects of Hesperidin on Insulin Sensitivity
Effects of Hesperidin on Insulin Sensitivity
This study will examine whether hesperidin, a major component of citrus fruits, affects how
 the body responds to insulin in healthy and obese people. Laboratory studies suggest that
 hesperidin treatment lowers blood pressure, lowers blood sugar and increases blood flow. This
 study will see if hesperidin improves insulin resistance or insulin's effects on blood flow
 in people with insulin resistance.

 Healthy normal weight or overweight people between 21 and 65 years of age may be eligible for
 this study. Participants are randomly assigned to take hesperidin or a placebo (inactive
 dummy pill ) for a 4-week treatment phase.
This study will examine whether hesperidin, a major component of citrus fruits, affects how
 the body responds to insulin in healthy and obese people. Insulin is not as effective in
 people who are overweight, have high blood pressure or diabetes. This condition is known as
 insulin resistance. Laboratory studies suggest that hesperidin treatment lowers blood
 pressure, lowers blood sugar and increases blood flow. This study will see if hesperidin
 improves insulin resistance or insulin's effects on blood flow in people with insulin
 resistance.

 Healthy normal weight or overweight people between 21 and 65 years of age may be eligible for
 this study. Participants are randomly assigned to take hesperidin or a placebo (inactive
 dummy pill ) for a 4-week treatment phase. In addition to treatment, participants undergo the
 following procedures during the study period:

 Screening, including medical history, physical examination and blood and urine tests.

 Complete a dietary and physical activity questionnaire and consult with a dietitian

 Blood and urine tests

 At-home and clinic blood pressure monitoring

 Glucose clamp test to measure how the body responds to insulin. This test is done two times
 during the study. A needle is placed in a vein in each of the subject's arms, one for
 sampling blood and the other for infusing insulin, glucose and potassium. Glucose and insulin
 levels, electrolytes, lipids, fatty acids, cytokines and hesperidin levels are measured. We
 will also use tracer-labeled glucose to determine how much glucose the body produces in the
 fasting state and during the clamp. This type of glucose has low levels of radiation.

 Forearm blood flow measurement with finger plethysmography device. Before beginning the
 glucose clamp test, a test of how well the blood vessels relax is done. A device that
 measures the blood flow in the vessels of the forefingers is used. The test is performed at
 the before the glucose clamp test and again 2 hours after the beginning of the clamp.
Inclusion Criteria:

 Healthy Subjects - Men and women in good general health with no significant underlying
 illnesses who are between the ages of 21 - 65 years of age with HbA1C < 5.7 %, fasting
 blood glucose < 100 mg/dL, blood pressure less than 120/80, and BMI between 20 - 25 kg/m2.
 Subjects should have never smoked tobacco or not smoked within the previous year.

 Obese Subjects - Men and women in good general health with no significant underlying
 illnesses except obesity who are between the ages of 21 - 65 years of age with HbA1C < 5.7
 %, fasting blood glucose < 100 mg/dl, blood pressure less than 130/90, and BMI between 30 -
 45 kg/m2.

 Exclusion Criteria:

 -  Subjects will be excluded from our study if they are pregnant, breastfeeding, or if
 they plan pregnancy prior to the end of the study. In addition, subjects will be
 excluded if their age > 65 yrs, BMI ≥ 45 kg/m2, or have liver disease (including liver
 transaminase levels greater than twice the upper limit of normal), pulmonary disease,
 renal insufficiency (serum creatinine greater than 2.0 mg/dl), coronary heart disease,
 heart failure (New York Heart Association heart failure Class III or IV), peripheral
 vascular disease, coagulopathy, Major depressive disorder, actively smoking or used
 tobacco within last year, history of cancer, in treatment for any form of cancer,
 positive tests for HIV, hepatitis B or C, or take systemic corticosteroids,
 thiazolidinediones (within 3 months), insulin, or anticoagulants, use food supplements
 that cannot be discontinued, regular intake of 8 or more cups of tea per week within 3
 months prior to study entry, regular alcoholic beverage intake of more than two drinks
 per day (a drink corresponds to approximately 12 ounces of beer, 4 ounces of table
 wine, and between 1 and 1.5 ounces of 80-proof spirits), poor compliance during run-in
 period or regular use of medications that affect insulin sensitivity, blood pressure
 or vascular function and that cannot be discontinued. In addition, history of any
 other medical disease, laboratory abnormalities, or psychological conditions that
 would make the subject (based upon the principal investigator's judgment) unsuitable
 for study enrollment. Subjects will be excluded if they are unable to give informed
 consent for all procedures.