The Effects of Bethanechol, a Muscarinic Agonist, on Plasma Insulin, Glucagon, and Glucose Levels in Humans With and Without Type 2 Diabetes Mellitus
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- The effects of Bethanechol on insulin secretion rates
Study Overview
Brief Summary
Xenin-25 and glucose-dependent insulinotropic polypeptide (GIP) are hormones produced in the intestine that are released into the blood immediately after ingestion of a meal. Together, these 2 hormones increase insulin release and reduce blood glucose levels. Xenin-25 works by increasing acetylcholine release in pancreatic islets. This study will determine if a Bethanechol, a drug that is similar to acetylcholine, also increases insulin release and reduces blood glucose levels after ingestion of a mixed meal.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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.
Arms & Interventions
Type 2 Diabetes Mellitus
Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (25 mg) (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Placebo (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (25 mg) (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (50 mg) (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (100 mg) (Drug)
Impaired Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Placebo (Drug)
Impaired Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (25 mg) (Drug)
Impaired Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (50 mg) (Drug)
Impaired Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (100 mg) (Drug)
Type 2 Diabetes Mellitus
Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Placebo (Drug)
Type 2 Diabetes Mellitus
Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (50 mg) (Drug)
Type 2 Diabetes Mellitus
Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.
Intervention: Bethanechol (100 mg) (Drug)
Outcomes
Primary Outcomes
The effects of Bethanechol on insulin secretion rates
Time Frame: 3 years
Insulin secretion rates (pmoles/min) will be calculated by deconvolution of plasma C-peptide levels. The investigators will then determine if post-prandial insulin secretion rates are greater following administration of Bethanechol compared to placebo.
Secondary Outcomes
No secondary outcomes reported