Modulating Glucose Tolerance With Dietary Tyrosine

Columbia University1 个研究点分布在 1 个国家目标入组 10 人开始时间: 2019年8月7日最近更新: 2021年5月5日

适应症

试验速览

阶段: 不适用
状态: 已完成
发起方: Columbia University
入组人数: 10
试验地点: 1
主要终点: Plasma insulin concentration

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Metabolic or Bariatric surgery is an effective treatment for type 2 diabetes mellitus (T2DM) diabetes associated with obesity. There remain some questions about the biochemical mechanism that drive how these surgeries work to reverse hyperglycemia. In the proposed human studies, the investigators will test the hypothesis that the amino acid tyrosine is a key metabolite in regulating blood sugar levels and that manipulation of the amount tyrosine supplied by nutrition is able to achieve some of the metabolic benefits seen in the early post-surgical period following bariatric surgery. The central hypothesis is that that the tyrosine content of the meal challenge affects post-prandial intestinal and plasma dopamine and levodopa and L-3,4-dihydroxyphenylalanine (L-DOPA) levels, which, in turn, impact β-cell insulin secretion and glucose excursions. The investigators now propose to characterize the possible effects of manipulating dopamine and L-DOPA levels in the gut and plasma on glucose tolerance, insulin secretion, and insulin sensitivity in healthy volunteers with a range of body mass indexes (BMIs).

详细描述

Several biochemical mechanisms explaining how Roux-en-Y Gastric Bypass (RYGB) provides an effective treatment for obesity associated type 2 diabetes mellitus (T2DM) and improves hyperglycemia independently of weight loss have been proposed. Two are of particular interest; a) the hindgut hypothesis suggesting that nutrient delivery to the distal intestine drives the production of "incretins" which enhance insulin secretion (e.g. glucagon-like peptide-1 (GLP-1)), and b) the foregut hypothesis, positing that foregut bypass reduces the secretion of factors (i.e. anti-incretins) that normally defend against hypoglycemia. The investigators have been actively investigating this topic and have developed a hypothesis based on past studies that they wish to test in a limited human clinical study. In addition, preclinical data suggest that there exists a gut-to-beta cell pathway, responsive to nutritional tyrosine, regulating insulin secretion, and this pathway provides a mechanism for the early postoperative improvements in hyperglycemia observed in RYGB.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Crossover
主要目的: Basic Science
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

未提供

排除标准

•Any diabetes medication within previous three (3) months.
•Fasting plasma Glucose (FPG) >126 mg/dl or HbA1c > 6.4%
•Current use (or within 6 months) of antipsychotic, anti-anxiety, or antidepressant medications (e.g. monoamine oxidase (MAO) inhibitors, 5-Hydroxytryptophan (5HT) inhibitors, tricyclic antidepressants, L-DOPA), reserpine, β-2-receptor agonists (e.g., terbutaline), steroids, weight loss medication, anticoagulant medication, over-the-counter nutritional supplements other than standard vitamin and mineral supplements
•History of Phenylketonuria or other inherited disorders of amino acid metabolism.
•History of movement disorder such as Parkinson's disease or Huntington's disease
•Cardiovascular, renal, pulmonary, gastrointestinal, migraines or other medical conditions deemed significant by investigators
•History of/ or psychiatric illness such as major depression, bipolar disease, anxiety or schizophrenia.
•History of bariatric surgery with the exception of gastric band if the band has been removed
•Female of child-bearing age, currently pregnant, breastfeeding or not using a form of birth control.
•Previous or current use of cocaine, methamphetamine, ecstasy (3-4 methylenedioxymethamphetamine (MDMA))
•Current daily intake of caffeine >500 mg/day (>4-5 cups of coffee; >10 12-oz cans of soda)
•Consumption of more than 1 alcoholic drink per day or smoking more than 5 cigarettes/day.
•Systolic Blood Pressure (SBP) > 150 mmHg; Diastolic Blood Pressure (DBP) > 100 mmHg.
•Recent history (in the past three months) of more than a 3% gain or loss in body wt.
•Difficulty in swallowing capsules.
•Concurrent use of antacids or proton pump inhibitors (e.g.,Prilosec Prevacid, dexilant, Aciphex, Protonix, Nexium, Vimovo, Zegerid)