Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Insulinotropic effects of GLP-1 and GIP
研究概览
简要总结
The aim of the study is to investigate the effect of Roux-en-Y gastric bypass (RYGB) on pancreatic alpha and beta-cell function and for the sensitivity of incretin hormones in patients with pre-operative type 2 diabetes.
Primary hypotheses:
- After RYGB, the sensitivity to GLP-1 and GIP is improved (improved insulinotropic effect).
- After RYGB, the insulin secretion improves during an oral glucose tolerance test within 3 months postoperatively.
- After RYGB, the insulin secretion during intraveneous stimulation with glucose or non-glucose (arginin) is unchanged.
详细描述
Design: 12 patients with type 2 diabetes will be recruited.
All subjects will undergo 11 study visits: four visits before, three visits at 1 week after surgery and four visits at 3 months postoperatively:
- Oral glucose tolerance tests (OGTTs) with measurement of GLP-1 and GIP secretion will be performed before and 3 months post-surgery.
- Hyperglycemic clamps with co-infusion of saline, GLP-1 or GIP will be performed in a randomised order at three separate study visits in randomized order before, 1 week and 3 months after surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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
- 否
入选标准
- •Inclusion criteria for RYGB in Denmark (ie. BMI > 35 in the presence of obesity related co-morbidities as type 2 diabetes)
- •Type 2 diabetes
- •Pre-operative: Fasting plasma glucose ≥7,0 mmol/L or 2 hour plasma glucose ≥ 11,1 mmol/L (after pausing antidiabetic medication for a minimum of 3 days)
- •Written informed consent.
排除标准
- •Exclusion criteria for RYGB (psychiatric illness, obesity triggered by medical treatment for psychiatric illness, mental retardation, alcohol or drug abuse, severe heart-lung disease despite optimal medical treatment, previous serious problems with universal anesthesia, previous peritonitis, large hiatus hernia, diseases of the ventricle / previously complicated upper abdominal surgery, recurrent esophagitis, poor compliance).
- •Type 2 diabetes where antidiabetic medication cannot be paused for 3 days.
- •Pregnancy and breast-feeding.
- •Hemoglobin <7.0 mmol/L
研究组 & 干预措施
Oral glucose tolerance test
Oral glucose tolerance test with ingestion of 75 g glucose and blood sampling.
This test will be performed before and 3 months after RYGB.
干预措施: Oral Glucose Tolerance Test (Diagnostic Test)
Hyperglycemic clamp with saline infusion combined with arginine test
Hyperglycemic clamp with blood glucose kept at 15 mmol/L by adjustable infusions of intraveneous glucose for 120 min with co-infusion of saline.
After 120 min an arginine test with infusion of 50 g Arginine is performed.
This test will be performed before, 1 week and 3 months after RYGB.
干预措施: Hyperglycemic clamp with infusion of saline, GLP-1 or GIP (Diagnostic Test)
Hyperglycemic clamp with GLP-1 infusion
Hyperglycemic clamp with blood glucose kept at 15 mmol/L by adjustable infusion of intraveneous glucose for 90 min with co-infusion of GLP-1.
This test will be performed before, 1 week and 3 months after RYGB.
干预措施: Hyperglycemic clamp with infusion of saline, GLP-1 or GIP (Diagnostic Test)
Hyperglycemic clamp with GIP infusion
Hyperglycemic clamp with blood glucose kept at 15 mmol/L by adjustable infusions of intraveneous glucose for 90 minutes with co-infusion of GIP.
This test will be performed before, 1 week and 3 months after RYGB.
干预措施: Hyperglycemic clamp with infusion of saline, GLP-1 or GIP (Diagnostic Test)
结局指标
主要结局
Insulinotropic effects of GLP-1 and GIP
时间窗: Change from before to 1 week and 3 months after RYGB
Insulin secretion during steady state of all hyperglycemic clamps
Insulin secretion during oral stimulation
时间窗: Change from before to 3 month after RYGB
AUC of C-peptide during oral glucose tolerance test
Insulin secretion during iv stimulation
时间窗: Change from before to 1 week and 3 months after RYGB
Insulin secretion during hyperglycemic clamp with saline infusion and during argininine iv stimulation test
次要结局
- Alpha cell function(Change from before to after 1 week and 3 months after RYGB)
研究者
Maria Saur Svane
MD, PhD
Hvidovre University Hospital