The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups
研究概览
简要总结
Patients with end-stage renal disease (ESRD) have a high prevalence of impaired glucose metabolism. The pathophysiological cause is uncertain, but disturbances in the secretion, elimination and effect of glucagon, insulin and the two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), probably play important roles. Our research group has previously found that dialysis patients without type 2 diabetes mellitus (T2DM) have a reduced incretin effect and an inability to suppress glucagon after a meal - two early pathophysiological characteristics of patients with T2DM and normal kidney function.
The aim of the project is to provide a detailed description of the mechanisms underlying the (patho)physiological effects of the incretin hormones in patients with ESRD. We plan to investigate the above mentioned disturbances during fasting and hyperglycaemic conditions using incretin infusions during glucose clamping. Furthermore, stable isotopic tracers will be used to determine the effect of the incretin hormones on the endogenous glucose handling.
We hypothesise that the effects of the incretin hormones in ESRD will be reduced in respect to healthy control subjects.
详细描述
The effect of the incretin hormones on the endocrine pancreatic function in a uremic environment will be explored during fasting and hyperglycemic conditions in three randomised examination days.
At a preceding screening day, an oral glucose tolerance test (OGTT) and a dual energy x-ray absorptiometry (DXA) scan will be performed to determine glucose tolerance and the distribution of muscle and adipose tissue. The study will be carried out on three separate days differing with respect to the hormones infused: GLP-1, GIP or placebo (saline) which are double blinded. The patients will meet from an overnight fast and an infusion of one of the hormones is initiated. At the same time labeled glucose will be infused to determine the endogenous hepatic glucose production. A glucose infusion is adjusted according to frequent plasma glucose measurements to maintain fasting glucose level. After 2 hours a steady state of the tracer is achieved and a 2 hour hyperglycemic clamp, 3 mmol/l above fasting glucose concentration will be started. The tracer infusions are continued during the hyperglycemia. After the 4 hour clamp an arginine bolus will be administered to measure the ability to increase the secretion of insulin and glucagon.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Fasting plasma glucose ≥ 6.1 mmol/l
- •2h plasma glucose ≥ 7.8 after ingestion of 75 grams of glucose
- •Admittance to a hospital
- •Anemia (Hb < 6.0 mmol/l)
- •Ongoing treatment with drugs interfering with glucose metabolism including steroids and calcineurin inhibitors
- •Bowel resection or any other large abdominal surgery
结局指标
主要结局
The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups
时间窗: Average during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes
Average plasma insulin concentrations during hyperglycemia
次要结局
- The effect of GLP-1 and GIP on insulin, glucagon and endogenous glucose production during euglycemia(Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes)
- The effect of GLP-1 and GIP on early and late phase of insulin, glucagon and endogenous glucose production during hyperglycemia(Averages during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes)
- The effect of GLP-1 and GIP on insulin and glucagon response to arginine(Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes)
- The effect of GLP-1 and GIP on the peripheral glucose handling(Average during the first 4 hours of each examination day. Blood samples are collected at 5-15 minutes interval from time 0 to time 240 minutes)
- The effect of GLP-1 and GIP on potassium concentrations during euglycemia(Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes)
研究者
Bo Feldt-Rasmussen
MD DMSc
Rigshospitalet, Denmark