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。根据对年轻患者(特别是PIMA印第安人后代)的小群研究，我们知道，儿童时期起病的T2 DM患者患糖尿病相关发病率和死亡率的风险非常高，这是因为糖尿病患者的终生病程较长，而且可能会增加β细胞衰竭的速度。 我们的主要研究目标是获得有关青年T2 DM自然病史的数据。测量将包括β细胞功能、身体成分、心血管疾病风险因素、胃肠激素和心理健康指数。这些数据将与瘦或超重/肥胖的非糖尿病志愿者的研究结果进行比较。 最近几项流行病学研究的数据表明，无糖汽水的摄入量与肥胖，甚至2型糖尿病之间存在联系。然而，没有证据表明两者之间存在因果关系。长期以来，人工甜味剂一直被认为是代谢惰性物质，因为它们不含或只含很少的卡路里。然而，来自啮齿动物研究的数据表明，人工甜味剂可能对血糖调节荷尔蒙有明显的影响，我们之前的初步研究证实，当葡萄糖餐之前先喝无糖苏打水时，GLP-1的反应性更强。 我们计划进一步确定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。这些受试者将接受反复的口服葡萄糖耐量测试或混合餐测试，然后饮用水或含三氯蔗糖的无糖苏打水。我们将调查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.