Effects of Quercetin on Blood Sugar and Blood Vessel Function in Type 2 Diabetes.

This is a phase II, crossover, double-blinded, controlled trial in 20 participants with type
2 diabetes designed to measure the effect of quercetin on glucose tolerance and postprandial
endothelial function in comparison to placebo and Acarbose. Glucose tolerance and insulin
excursion will be measured at 0, 30, 60, and 120 minutes following a 100g maltose tolerance
test (MTT). Each participant will blindly rotate between three single individual doses of
placebo, quercetin (2g oral), and Acarbose (100mg oral) prior to the MTT on 3 separate
occasions. Each participant will serve as their own control and comparison for each of the
interventions.

Fasting and post-MTT endothelial function will be measured by peripheral tonometry (Itamar
EndoPAT (Peripheral Arterial Tone) 2000) and reported as reactive hyperemia index (RHI).
EndoPAT testing will be performed prior to the fasting blood collection and then again at 90
minutes following the MTT, during each clinical research visit.

Exploratory data will also be collected on post-MTT increases in gamma-glutamyltransferase
(GGT).

Inclusion Criteria:

- Adults aged 18-75 years with the International Classification of diseases book 9
(ICD-9) diagnosis of type 2 diabetes (250.XX). As lack of clarity in ICD-9 coding by
providers is notorious in type 2 diabetes, we will specify ICD-9 diagnosis 250.XX in
order to capture all subtypes of type 2 diabetes (see ICD-9 book for more information
on subtypes).

- Patients on a stable dose (consistent dose for one month) of all medications and
supplements.

- Hemoglobin A1c (HbA1c) of 6.5-10.5% within the last year. Since quercetin's effect on
blood sugar and endothelial function may be related to its anti-oxidant properties,
we are interested in looking at is effect on patients with higher levels of oxidative
damage associated with higher blood sugars (i.e. elevated HbA1c > 6.5%), yet we will
exclude those with severe hyperglycemia.

- Stable exercise and diet for last 1 month.

- Labs (HbA1c, aspartate aminotransferase (AST), Alanine transaminase (ALT), Glomerular
filtration rate (GFR), and creatinine) measured within the last year and meet
inclusion/exclusion criteria or we will run them.

Exclusion Criteria:

- Current use of insulin or Acarbose (due to possible hypoglycemia); insulin exclusion
will ensure exclusion of those with type 1 diabetes.

- Current use of quercetin.

- History of myocardial infarction within the last 6 months, angina, ischemic stroke,
uncontrolled hypertension with systolic greater than 180 or diastolic greater than
110.

- Clinical or objective finding suggestive of congestive heart failure Class III or IV
or shortness of breath with Activities of Daily Living (ADLs).

- Recent (<14 days) history of infection. During the telephone screening, if patients
have had an acute infection in the last 14 days they will be asked if we may
recontact them in 3-4 weeks for a second telephone screening to determine
qualification (including resolution of their recent infection > 14 days).

- Stage IV or higher kidney disease (eGFR < 30).

- Liver disease (defined as AST or ALT > 2 x high normal (according to lab range)).

- Prior diagnosis of genetic abnormalities of carbohydrate metabolism (e.g. Congenital
Sucrase-Isomaltase, Pompe Disease).

- Pregnant or breast feeding.

- Mental illness or other cognitive impairment prohibiting the candidate from making an
informed choice (determined at the discretion of the PI in consult with the Research
Assistants/Study Coordinator as needed) as assessed throughout telephone screening
and informed consent process.

- Hypersensitivity to quercetin or Acarbose; based on past allergic symptoms taken with
either drug or drug or supplement.

- Diagnosis of celiac disease/"sprue".

- Contraindications for EndoPAT:

- Participants on anti-platelet medications will be excluded if they have visible
bruising (beyond petechiae).

- Participants will be excluded if they are unwilling to fast for 12 hours prior to
maltose tolerance test and/or EndoPAT.

- Participants will be excluded if they have taken nitroglycerine, Cialis, or Viagra 12
hrs before test days.

- In order to accommodate the finger probes, participants will be excluded if they are
unwilling to clip their fingernails on their index finger short prior to test days.
Index finger nail must not extend past their finger on test days.

- Bilateral upper extremity lymphedema.

- Contraindications for Acarbose:

- Current diabetic ketoacidosis.

- Inflammatory bowel disease; colonic ulceration; partial intestinal obstruction, or in
patients predisposed to intestinal obstruction; chronic intestinal diseases with
marked maldigestion or malabsorption; hernia.

- Cirrhosis

- Renal impairment (serum creatinine > 2 mg/dL).