Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Blood Sugar, Xenin-25, GIP, Insulin
Brief summary
An intestinal hormone called Glucose-dependent Insulinotropic Polypeptide (GIP) is released into the blood immediately after ingestion of a meal and plays an important role in regulating blood sugar levels. However, GIP is not active in persons with type 2 diabetes mellitus (T2DM) which is also known as adult onset or non-insulin-dependent diabetes. This study is being conducted to determine whether a hormone called xenin-25 can restore the activity of GIP in persons with T2DM.
Detailed description
Each eligible participant will be administered an oral glucose tolerance test so he/she can be assigned to the group with normal glucose tolerance, impaired glucose tolerance (between normal and diabetic), or type 2 diabetes mellitus. 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 primed-continuous infusion of vehicle alone, GIP alone, xenin-25 alone, or the combination of GIP plus xenin-25 (each peptide at a dose of 4 pmoles x kg-1 x min-1) will be initiated at the same time the meal is ingested. Blood samples will be collected before and during the MTT for the measurement of glucose, insulin, C-peptide, glucagon, GIP and xenin-25 levels.
Interventions
DRUGPlacebo
Intravenous infusion of 1% human albumin in normal saline
Intravenous infusion of GIP (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
DRUGXenin-25
Intravenous infusion of xenin-25 (4 pmoles x kg-1 x min-1) in 1% human albumin in normal saline
Intravenous infusion of GIP plus xenin-25 (4 pmoles each x kg-1 x min-1) in 1% human albumin in normal saline
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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. * Willingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be made to complete this visit during study participation.
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. * Subjects unwilling to allow the use of their own blood or the human albumin in the preparation of the peptides. * Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| We will develop an assay to measure the normal fasting and postprandial concentrations of endogenous xenin-25 and determine whether they are altered in T2DM. | 3 years |
Countries
United States
Outcome results
None listed