Studies in Youths & Young Adults with Obesity & T2DM (07-DK-0115, 10-DK-0163)

背景 2型糖尿病（T2 DM）是一种以胰岛素抵抗和胰岛素分泌β细胞进行性衰竭为特征的疾病。 基于对年轻患者（尤其是皮马印第安人后代）的小队列研究，我们知道儿童期发病的T2 DM个体发生糖尿病相关发病率和死亡率的风险非常高，这是由于糖尿病的生命持续时间较长，以及β细胞衰竭的速度可能加快。 我们的主要研究目标是获得青年T2 DM自然史的数据。 测量将包括β细胞功能，身体成分，心血管疾病风险因素，肠道激素和心理健康指数。 将这些数据与非糖尿病志愿者（瘦或超重/肥胖）的结果进行比较。 最近几项流行病学研究的数据表明，无糖汽水消费、肥胖甚至2型糖尿病之间存在联系。但是，没有证据表明存在因果关系。人造甜味剂长期以来被认为是代谢惰性物质，因为它们不含或含有很少的卡路里。然而，来自啮齿动物研究的数据表明，人工甜味剂可能对葡萄糖调节激素有明显的影响，我们之前的初步研究已经证实，当葡萄糖餐之前有无糖苏打水时，GLP-1的反应性更大。 我们计划进一步表征食用人工甜味剂对肠道的影响，并将招募健康志愿者以及1型和2型糖尿病患者。 这些受试者将接受重复的口服葡萄糖耐量试验或混合餐试验，然后饮用水或含三氯蔗糖的饮食苏打水。 我们将研究重复测试之间胰岛素、葡萄糖或其他激素水平的差异。

Background Type 2 diabetes mellitus (T2DM) is a condition characterized by insulin resistance and progressive failure of the insulin-secreting beta-cells. Based on studies in small cohorts of young patients (especially Pima Indian offspring), we know that individuals with childhood onset T2DM are at very high risk for diabetes-related morbidity and mortality, due to a longer life-time duration of diabetes, as well as possible increased rapidity of beta-cell failure. Our primary study objective is to acquire data on the natural history of T2DM in youth. Measurements will include indices of beta-cell function, body composition, cardiovascular disease risk factors, gut hormones, and psychological well-being. These data will be compared to findings in non-diabetic volunteers who are lean or overweight/obese. Data from several recent epidemiologic studies have indicated a link between diet soda consumption, obesity, and even type 2 diabetes. However, there is no evidence for a causal relationship. Artificial sweeteners have long been regarded as metabolically inert substances since they contain no or very few calories. Yet, data from rodent studies show that artificial sweeteners may have distinct effects on glucoregulatory hormones and our previous pilot study has confirmed a greater responsiveness of GLP-1 when a glucose meal was preceded by diet soda. We plan to further characterize effects of consumption of artificial sweeteners on intestinal and will enroll healthy volunteers, as well as subjects with type 1 and type 2 diabetes. These subjects will undergo repeated oral glucose tolerance tests or mixed meal tests, preceded by consumption of a water or a sucralose-containing diet soda. We will investigate differences in insulin, glucose, or other hormone levels between the repeated tests.