Role of Alpha-cell GLP-1 in the Beta-cell Response to DPP-4 Inhibition
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Arginine-stimulated Insulin Secretion With and Without GLP-1 Blockade
研究概览
简要总结
This study is being done to determine the role of a hormone, glucagon-like peptide 1 (GLP-1), on insulin secretion and to study how GLP-1 works in in diabetic individuals as compared to non-diabetic individuals, under fasting conditions.
GLP-1 is a naturally occurring hormone made in the intestines. It is released into the circulating blood after eating and helps to control the blood glucose levels by increasing insulin secretion by cells in the pancreas. However, the exact method by which GLP-1 causes insulin secretion and how GLP-1 activity is changed in diabetic persons remain unclear. This research is being done to address these questions and better understand the function of GLP-1.
In this research, the investigators will use a synthetic form of Exendin-9 to determine the effects of GLP-1 on insulin secretion in diabetic and non-diabetic persons. Exendin-9 acts as a blocker of GLP-1 action, allowing us to study the specific effects of the GLP-1 hormone. Exendin-9 is an investigational compound, which means it is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA).
In this study, the investigators will also use the drug Sitagliptin, which is an FDA-approved drug for the treatment of type 2 diabetes mellitus. In this study, use of Sitagliptin is considered investigational since it is not being used for treatment of diabetes but is instead being used to understand how GLP-1 works and to better understand how medications like Sitagliptin work in patients with type 2 diabetes mellitus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diabetic cohort: adults age 35-70 years with Type 2 diabetes managed by an oral medication or diet and exercise
- •Non-diabetic cohort: healthy adults age 35-70 years
- •Male or female
- •Ability to speak and understand English
- •Diabetic cohort: HbA1c ≤ 8.0%
- •Non-diabetic cohort: HbA1c ≤ 6.2%
排除标准
- •Rheumatoid arthritis
- •Inflammatory bowel disease
- •Unstable angina or uncompensated heart failure
- •Pulmonary disorders, including COPD and asthma
- •Malabsorptive GI disease, such as celiac disease, or gastric bypass
- •Significant hepatic disease
- •Renal insufficiency (eGFR < 60 mL/kg/min)
- •Anemia (hematocrit < 34%) as measured at screening visit
- •Uncontrolled hypertension
- •Pregnant females
- •Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
- •Consumption or injection of insulin
- •Apparent sensitivity to any of the study peptides as determined by the skin test
研究组 & 干预措施
Non-Sitagliptin
The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, placebo will be administered
干预措施: Placebo Comparator - No Sitagliptin (Drug)
结局指标
主要结局
Arginine-stimulated Insulin Secretion With and Without GLP-1 Blockade
时间窗: 30 minutes
The investigators will use the mean increment of insulin secretion rate above baseline in the 30 minutes after Arginine stimulation to integrate insulin secretion, the primary outcome measure, and 2-way ANOVA with and without Sitagliptin and Ex-9/saline at the two factors.
次要结局
未报告次要终点
研究者
David D'Alessio, M.D.
Professor, Division Chief of Endocrinology Division
Duke University