Restoration of the GIP-mediated Incretin Effect in Persons With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 <
- •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
研究组 & 干预措施
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
干预措施: Placebo (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
干预措施: Glucose-dependent Insulinotropic Polypeptide (GIP) (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
干预措施: Xenin-25 (Drug)
Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
干预措施: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 (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.
干预措施: 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.
干预措施: Glucose-dependent Insulinotropic Polypeptide (GIP) (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.
干预措施: Xenin-25 (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.
干预措施: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 (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.
干预措施: 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.
干预措施: Glucose-dependent Insulinotropic Polypeptide (GIP) (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.
干预措施: Xenin-25 (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.
干预措施: Glucose-dependent Insulinotropic Polypeptide plus Xenin-25 (Drug)
结局指标
主要结局
The effects of GIP, xenin-25, or a combination of GIP plus xenin-25 on insulin secretion and blood glucose levels
时间窗: 5 years
次要结局
- The effects of xenin-25 on GIP action in persons with type 2 diabetes(5yrs)