Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance
研究概览
简要总结
RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls.
详细描述
RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
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
- •Hypoglycemic RYGB patients with documented blood glucose level <50 mg/dl
- •Asymptomatic individuals with bariatric surgery
- •Healthy non-surgical patients with no personal history of diabetes
- •Subjects must physically be able to come to our clinical research center at Cedars-Sinai Medical Center
排除标准
- •Active heart, lung, liver, gastrointestinal or kidney disease; unable to give informed consent; pregnancy; uncontrolled high blood pressure or high cholesterol; significant anemia (hemoglobin <11g/dL); prisoners or institutionalized individuals; type 2 diabetes melitis; development of any serious medical or psychiatric illness during recruitment or studies;
- •RYGB patients will also be disqualified if they have gastric outlet obstruction or severe diarrhea
- •Healthy non-surgical patients with personal history of diabetes
- •For administration of atropine, the following exclusions also apply:
- •History of glaucoma
- •Uncontrolled hypertension (any subjects with BP>140/90 and history of dyslipidemia
- •Taking any medication that might interact with atropine and cannot be stopped will be excluded from the study)
- •Myasthenia gravis
- •Brain pathology
- •Enlarged prostate in men
研究组 & 干预措施
Exendin-(9-39)
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
干预措施: Exendin-(9-39) (Drug)
atropine
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
干预措施: Atropine (Drug)
GLP-1 and GIP
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
干预措施: GLP-1 and GIP (Drug)
结局指标
主要结局
Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance
时间窗: Each study of the protocol is conducted up to seven hours with data collected at intervals specific to the individual study procedure.
次要结局
未报告次要终点