The Effects of Bethanechol on Glucose Homeostasis

Each eligible participant will be administered an oral glucose tolerance test (OGTT) so
he/she can be assigned to the group with normal glucose tolerance (NGT), impaired glucose
tolerance (IGT) which is between normal and diabetic, or type 2 diabetes mellitus (T2DM).
Each study subject will then be administered a meal tolerance test (MTT) on 4 separate
occasions. For the MTT, a liquid meal (Boost Plus) will be ingested following an overnight
fast. A placebo or Bethanechol (25 mg, 50 mg, or 100 mg) will taken by mouth 1 hour before
ingestion of the meal. Blood samples will be collected before and during the MTT for the
measurement of glucose, insulin, C-peptide, and glucagon levels.

Inclusion Criteria:

- Ages 18-65. No minors will be studied.

- Individuals must be able to consent for their own participation (no mental impairment
affecting cognition or willingness to follow study instructions).

- Healthy volunteers with no clinical evidence of T2DM (see below).

- Otherwise healthy volunteers that have impaired glucose tolerance (see below).

- Otherwise healthy volunteers with Diet Controlled T2DM (see below).

- Otherwise healthy volunteers with T2DM that take oral agents only and if the subject's
pre-existing oral anti-diabetic agents can be safely discontinued for 48 hours prior
to Oral Glucose Tolerance Test.

- Otherwise healthy volunteers with T2DM who do not use insulin for blood glucose
control.

- Persons with HbA1c ≤ 9%.

- Women of childbearing potential must be currently taking/using a method of birth
control that is acceptable to the investigators. A pregnancy test will be done at the
beginning of each visit. Any woman with a positive pregnancy test will be removed from
the study.

Exclusion Criteria:

- <18years of age or >65 years of age

- Lacks cognitive ability to sign the consent &/or follow the study directions for
themselves

- Women unwilling to comply with using an acceptable method of contraception during the
course of the study, or who are currently breast-feeding.

- Any subject whose screening HbA1c is >9.0%

- Type 2 diabetes requiring the use of supplemental insulin @ home

- Volunteers with a history of Acute Pancreatitis

- Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic
pancreatitis including hypertriglyceridemia (triglycerides >400mg/ml) hypercalcemia
(blood calcium level >11.md/dl) and/or the presence of gallstones.

- Volunteers with a history of gastrointestinal disorders, particularly related to
gastric motility/emptying such as gastric bypass, documented gastro-paresis in
diabetic volunteers.

- Volunteers with a history of cancer. Exception: skin cancer.

- Diabetics that have the potential to have a low blood sugar without them being aware
that their blood sugar is low (hypoglycemia unawareness).

- Known heart, kidney. liver or pancreatic disease requiring medications.

- Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin.

- Subjects with hyperthyroidism, coronary artery disease, peptic ulcer, asthma, chronic
bronchitis, or COPD.