Study of the Effects of Xenin-25 in Humans With and Without Type 2 Diabetes Mellitus
- Conditions
- Diabetes
- Interventions
- Drug: PlaceboDrug: Glucose-dependent Insulinotropic Polypeptide (GIP)Drug: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25
- Registration Number
- NCT00798915
- Lead Sponsor
- Washington University School of Medicine
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Impaired Glucose Tolerance Xenin-25 Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose. Normal Glucose Tolerance Xenin-25 Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose. Normal Glucose Tolerance Placebo Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose. Normal Glucose Tolerance Glucose-dependent Insulinotropic Polypeptide (GIP) Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose. Normal Glucose Tolerance Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose. Impaired Glucose Tolerance Placebo Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose. Type 2 diabetes mellitus Placebo 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. Impaired Glucose Tolerance Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose. Impaired Glucose Tolerance Glucose-dependent Insulinotropic Polypeptide (GIP) Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose. Type 2 diabetes mellitus Glucose-dependent Insulinotropic Polypeptide (GIP) 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. Type 2 diabetes mellitus Xenin-25 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. Type 2 diabetes mellitus Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 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.
- Primary Outcome Measures
Name Time Method The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels 5 years
- Secondary Outcome Measures
Name Time Method The effects of xenin-25 on GIP action in persons with type 2 diabetes 5yrs
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States