The Effects of Experimental Elevation of Plasma Glucose and Lipid on Pancreatic Beta-cell Function in Humans
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Insulin Secretion
研究概览
简要总结
Elevations of blood glucose and lipid are thought to be deleterious to the insulin secretory function of the pancreas. This is known as glucolipotoxicity. However, few studies have examined this in detail. This investigation will examine pancreatic insulin secretory function in physiological models of glucolipotoxicity such as obese and type 2 diabetic individuals. Furthermore, healthy subjects will undergo 24 hour infusion of glucose or Intralipid to induce experimental models of glucolipotoxicity. Insulin secretion in response to intravenous infusions of glucose, GLP-1, GIP, and arginine and in response to meal ingestion, will be examined. the investigators hypothesize that experimental glucolipotoxicity will impairs pancreatic insulin secretory function to levels akin to that seen in type 2 diabetics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 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
- •normal glucose tolerance based on screening OGTT or
- •diagnosed type 2 diabetic (confirmed with OGTT)
排除标准
- •insulin dependent diabetes
- •age <18 or >65 years
- •BMI <20 or > 35 kg/m2
- •evidence of hematological, pulmonary, hepatic, renal, or cardiovascular disease
- •actively undergoing weight-loss (>2kg change in last 6 months)
- •bariatric surgery (gastric by-pass or banding)
- •pregnancy
研究组 & 干预措施
Glucotoxicity Trial
Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions.
The clamp will be performed before and after 24 hours of bed rest, isocaloric meal feeding, and experimental elevation of blood glucose.
干预措施: Glucotoxicity (Procedure)
Control Trial
Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions.
The clamp will be performed before and after 24 hours of bed rest and isocaloric meal feeding.
Lipotoxicity Trial
Insulin secretion will be assessed using a hyperglycemic clamp combined with GLP-1, GIP, and arginine infusions.
The clamp will be performed before and after 24 hours of bed rest, isocaloric meal feeding, and experimental elevation of blood free fatty acids.
干预措施: Lipotoxicity (Procedure)
结局指标
主要结局
Insulin Secretion
时间窗: 24 hours
Insulin secretion will be assessed in response to intravenous infusions of glucose, GLP-1, GIP, and arginine, and in response to meal ingestion.
次要结局
- Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra)(24 hours)
- Insulin Sensitivity(24 hours)
研究者
Thomas Solomon
Group Leader
Rigshospitalet, Denmark