study of the effects of xenin-25 in humans with and without type 2 diabetes mellitus

Conditions: Diabetes

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.

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.

Eligibility criteria:
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

Keywords: diabetes blood sugar xenin-25 gip insulin