The Role of the Duodenum in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 19
- 主要终点
- Insulin sensitivity
研究概览
简要总结
In parallel with the increasing prevalence of obesity worldwide, type 2 diabetes mellitus (T2DM) has reached epidemic proportions. Despite a multitude of available therapies, only bariatric surgery (e.g., roux-en-Y gastric bypass (GBP)) has proven to be an effective long term treatment modality for morbid obesity. Moreover, the majority of T2DM patients who undergo GBP experience normalization of their blood glucose and are able to discontinue their anti-diabetes medications soon after the procedure. The insulin resistant state commonly seen in non-diabetic obese subjects also improves after GBP. Evidence from recent animal studies suggests that the rapid return to euglycemia seen in T2DM patients after GBP might in part result from excluding the duodenum from the flow of nutrients. With the use of enteral feeding tubes, we hope to better understand the factors in the human gut that may predispose obese individuals to the development of insulin resistance and T2DM.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for lean, healthy control subjects:
- •Fasting plasma glucose (FPG) < 100
- •Age 18 to 55
- •BMI 18.5 to 24.9 kg/m2
- •Stable weight for prior 3 months
- •Inclusion criteria for prediabetic individuals:
- •Based on American Diabetes Association criteria of FPG > 100 and <126
- •Age 18 to 55
- •BMI 35 to 60 kg/m2
- •Stable weight for prior 3 months
- •Inclusion criteria for diabetic individuals:
- •Diagnosis of type 2 diabetes mellitus (T2DM) for < 5 years
- •Hemoglobin A1c < 8%
- •Age 18 to 55
- •BMI 35 to 60 kg/m2
- •Stable weight for prior 3 months
排除标准
- •Exclusion criteria for all study subjects:
- •Use of any of the following medications: Thiazolidinediones, dipeptidyl-peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin), GLP-1 analogs (e.g., exenatide).
- •Subjects with T2DM who are unable to maintain adequate glycemic control (i.e., having a fasting blood glucose that exceeds 250mg/dL on two consecutive tests) while temporarily discontinuing their oral diabetes medications for the study and in whom the study physician determines insulin therapy would not be appropriate.
- •Females with a positive pregnancy test
- •Prior gastric, duodenal, proximal jejunal surgery or pancreas resection
- •Known malabsorptive disorder
- •History of cancer in past 5 years
- •Renal insufficiency defined by serum creatinine > 1.5 mg/dl
- •Hepatic enzyme elevations of greater than twice the upper limits of normal
- •Current use of warfarin or clopidogrel
- •Intercurrent infections
- •Contraindication to nasogastric or nasojejunal feeding tube (e.g., deviated nasal septum, prior upper gastrointestinal bleed, or history of easy bleeding)
- •Residence outside the greater Nashville, TN area
结局指标
主要结局
Insulin sensitivity
时间窗: 3 days
次要结局
- Incretin effect(3 days)
研究者
Naji Abumrad
Chairman, Department of Surgery
Vanderbilt University