Diabetes
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 graded glucose infusion (GGI) on 4 separate occasions. For the GGI, an intravenous glucose infusion will be started at a rate of 1 mg x kg-1 x min-1 for 40 min, followed by 2, 3, 4, 6, and 8 mg x kg-1 x min-1 (40 min for each step). 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 glucose infusion is started. Blood samples will be collected before and during the GGI 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
* 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. * Otherwise healthy volunteers that have impaired glucose tolerance. * Otherwise healthy volunteers with diet controlled T2DM. * Otherwise healthy volunteers with T2DM that take oral agents only if the subject's pre-existing oral anti-diabetic agents can be safely discontinued for 48-hours. * Persons with HbA1c less than 9%. * Women of childbearing potential must be currently taking/using an acceptable method of birth control. 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 complete all required visits.
Exclusion criteria
* Lacks cognitive ability to sign the consent or follow the study directions. * Women unwilling to use 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 at home. * Volunteers with a history of Acute Pancreatitis. * Volunteers with a history of cancer (except for skin cancer). * 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. * Subjects taking medications known to affect glucose tolerance. * Hematocrit from the lab is below 33% (or if the finger stick hemoglobin measured with the HemoCue 201+ is \<11.2% mg/dlL). * Diabetics that have the potential to have a low blood sugar without them being aware that their blood sugar is low (hypoglycemia unawareness). * Significant systemic illness including heart, kidney, inflammatory, liver, or malignant disease requiring medications. * Subjects will be excluded if their liver or kidney function is outside the upper limits of normal by \> 3%. Total Bilirubin levels should be \<2. * Subjects unwilling to allow the use of 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 | 5 years |
Secondary
| Measure | Time frame |
|---|---|
| The effects of xenin-25 on GIP action in persons with type 2 diabetes | 5yrs |
Countries
United States
Outcome results
None listed