• Efficacy of quercetin on blunting hyperglycemia [ Designated as safety issue: No ]
  

Procedure: Oral glucose tolerance test
N/A

Postprandial hyperglycemia and the resultant hyperinsulinemia contribute to the cardiovascular complications seen in obesity and in type 2 diabetes. Epidemiological studies suggest that slow absorption of carbohydrates dampens glucose and insulin peaks, and reduces cardiovascular morbidity. The polyphenol quercetin is the most abundant flavanoid in plant-derived foods, and is sold as a dietary supplement. In vitro, quercetin is a potent and reversible inhibitor of glucose transport by the intestinal glucose transporter GLUT2. In vivo quercetin inhibits post absorptive glucose peaks in obese, diabetic rats. We hypothesize that quercetin blunts intestinal glucose absorption in humans, and attenuates postprandial hyperglycemia. We propose to test, in a double blind placebo controlled study, whether coadministration of 1 or 2 grams of quercetin with 50 grams of glucose will reduce plasma glucose concentrations during a 6 hour 50g oral glucose tolerance test in non-diabetic obese subjects and in obese type 2 diabetic subjects. Study subjects will be 19-65 years with a body mass index greater than or equal to 30, without complications of diabetes, or on any medication other than oral hypoglycemic agents and aspirin. We will study 16 obese non diabetic subjects and 16 obese type 2 diabetic. Each subject will have 3 oral glucose tolerance tests, and will serve as his or her own control. We will compare the peak plasma glucose concentrations achieved during oral glucose tolerance tests and the area under the curve of plasma glucose to determine whether quercetin inhibits glucose absorption in humans. Such inhibition may partially explain the protective effects of plant derived foods on cardiovascular disease, and enable us to use quercetin or related compounds to dampen intestinal glucose absorption.

• INCLUSION CRITERIA:

Subjects to be recruited for the study will be male and female subjects between the ages of 19 and 65, able to give informed consent, with mild to moderate type 2 diabetes (on treatment with diet alone and/or submaximal doses of oral hypoglycemic agents only such that fasting blood sugar less than 200mg/dl or HbA1c less than 8.5; insulin treatment is not allowed), in otherwise good general health, with no other significant illnesses, blood pressure 160/90, with no known target organ damage, and on no medications other than oral hypoglycemic agents and/or aspirin.

End organ damage includes the following: proliferative retinopathy, serum creatinine greater than 2, ischemic heart disease, congestive heart failure, peripheral vascular disease and peripheral neuropathy.

Diabetics must have a BMI greater than or equal to 30.

Subjects will be taken off hypoglycemic agents at least one week prior to each part of the study. This is to remove a confounding factor that may affect blood glucose concentrations attained during the OGTT, independent of the effect of quercetin. Whether these oral hypoglycemic agents have physiologically significant interaction with quercetin is not known.

During the time that the subjects are off oral hypoglycemic agents, they will monitor their fasting blood glucose daily by glucometer. Therefore, only subjects who self monitor blood glucose are eligible for inclusion. If the fasting blood glucose exceeds 300 mg/dl, the subject will be withdrawn from the study and appropriate therapy resumed.

Obese volunteers, with a BMI greater than or equal to 30, must be in good health, with no known illness and should not be on any regular medication other than aspirin.

An upper age limit of 65 years was chosen to minimize renal toxicity of quercetin, as GFR declines with age and quercetin might produce mild though reversible renal impairment.

EXCLUSION CRITERIA:

Exclusion criteria will include the following: significant digestive abnormalities such as malabsorption or chronic diarrhea; significant organ malfunction including (but not limited to) liver disease, pulmonary disease, ischemic heart disease, heart failure, stroke, peripheral vascular disease, hypertension (BP greater than 160/90), and anemia (hematocrit less than 30); other serious or chronic illness; history of serious or chronic illness; any significant complications from diabetes such as kidney damage (renal insufficiency, serum creatinine greater than 2), eye damage (proliferative retinopathy), diabetic neuropathy, coronary artery disease, or peripheral vascular disease; smoking; use of medications (other than hypoglycemic agents or aspirin), alcohol or drug abuse, smokers; insulin treatment; pregnancy (a urine pregnancy test will be performed on all women with reproductive age before each part of the study); positive HIV or hepatitis (B or C) screening tests (subjects will be notified of these test results).

Those on oral contraceptives are not eligible for the study.

Patients on antihypertensive medication are excluded even if blood pressure is well controlled because antihypertensive medication may affect blood glucose during OGTT, thus introducing a confounding variable.

Whether antihypertensive medication interacts with quercetin is not known. Further, quercetin may cause reversible renal impairment, and hypertension is an important cause for renal disease.

Patients on oral contraceptive medication are excluded for similar reason, that is to avoid the possible confounding effect of oral contraceptives on blood glucose during an OGTT.