Saccharin and Acesulfame Potassium Consumption and Glucose Homeostasis in Older Adults with Prediabetes

1个项目摘要 2观察性研究已经将非营养性甜味剂(NNS)的摄入联系在一起，这些甜味剂 每天增加约50%的美国中老年人，并增加患2型糖尿病(T2D)的风险。这一风险 4增龄可能会加剧，这与低级别的慢性炎症和 5患T2D的风险增加。目前与NNS使用相关的T2D预防建议尚不清楚 6和令人困惑的；建议用作添加糖摄入量的替代品，但长期使用NNS是 7.尽管只有最少的研究来支持这一建议，但仍令人沮丧。动物学和观察学 8人体研究表明，一些NNS对血糖稳态有不利影响。更长期的人类 9项研究在很大程度上证明了零发现。研究设计的差异和现有研究缺乏严谨性 10研究有助于得出不确定的结论。此外，神经网络通常还被作为一个单独的实体来研究 11种NN的吸收和代谢不同(例如，两种常用的NN，糖精 12和乙酰磺胺钾[Ace-K])。NNS的摄入是否影响血糖的动态平衡 13名患有前驱糖尿病的中老年患者尚不清楚，其可能的机制是 发生的14起尚未确定。此R21提案的总体目标是建立以下证明 15摄取糖精后血糖稳态改变的概念，但不是Ace-K，在中期- 16名患有糖尿病前期的老年人与无神经营养不良的无糖饮食进行比较。我们会调查的 17炎症标志物的变化是糖精摄入影响的潜在机制 18葡萄糖动态平衡。在两周的无糖饮食后，51名中老年人(50岁以上) 19名糖尿病前期患者将被随机分配到3种受控喂养条件中的一种，为期6周(17 每组20名参与者)：糖精、Ace-K或对照组(不含NNS)。标准化饮食将是 21大量营养素(50%碳水化合物、35%脂肪、15%蛋白质)和其他变量匹配，以避免 22体重变化和可能影响研究结果的饮食因素的潜在混淆 23(例如，添加糖)。除了两组额外的NN外，所有组都将获得相同的饮食 24个NNS组。使用连续血糖监测和胰岛素敏感性进行24小时血糖控制 25通过静脉葡萄糖耐量试验(IVGTT)、血清内毒素和炎症反应检测β细胞功能 包括C反应蛋白在内的26种细胞因子将在为期6周的饮食前后进行检测 27个疗程。这项研究可能会有临床实践和政策影响，因为它告诉美国。 28个饮食指南和T2D预防指南，对NNS和 29对NNS的使用提供不明确的指导，这主要是因为缺乏严格设计的控制喂养 30次试验。

1 Project Summary 2 Observational research has linked intake of non-nutritive sweeteners (NNS), which are consumed 3 daily by ~50% of middle-aged/older U.S. adults, with increased risk of type 2 diabetes (T2D). This risk 4 may be exacerbated by advancing age, which is associated with low-grade chronic inflammation and 5 increased risk of T2D. Current T2D prevention recommendations related to NNS usage are unclear 6 and confusing; use as an alternative to added sugar intake is suggested but long-term NNS use is 7 discouraged despite minimal research to support this recommendation. Animal and observational 8 human studies suggest detrimental effects of some NNS on glucose homeostasis. Longer-term human 9 studies largely demonstrate null findings. Differences in study design and a lack of rigor in existing 10 research contribute to inconclusive findings. In addition, NNS are often studied as a single entity yet 11 types of NNS vary in their absorption and metabolism (e.g., two commonly consumed NNS, saccharin 12 and acesulfame potassium [Ace-K]). Whether NNS consumption impacts glucose homeostasis in 13 middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could 14 occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of- 15 concept for alterations in glucose homeostasis following intake of saccharin, but not Ace-K, in middle- 16 aged/older adults with prediabetes compared to a eucaloric diet with no NNS. We will investigate 17 changes in inflammatory markers as potential mechanisms by which saccharin intake influences 18 glucose homeostasis. Following a 2-week eucaloric lead-in diet, 51 middle-aged/older adults (50+ yrs) 19 with prediabetes will be randomly assigned to 1 of 3 controlled feeding conditions for 6 weeks (17 20 participants per group): saccharin, Ace-K, or a control group (no NNS). Standardized diets will be 21 matched for macronutrients (50% carbohydrate, 35% fat, 15% protein) and other variables to avoid 22 the potential confounds of weight change and dietary factors which may influence study outcomes 23 (e.g., added sugars). All groups will receive identical diets, other than the additional NNS for the two 24 NNS groups. 24-hr glycemic control using continuous glucose monitoring and insulin sensitivity and 25 beta cell function via intravenous glucose tolerance test (IVGTT), serum endotoxin, and inflammatory 26 cytokines, including C-reactive protein, will be measured before and following the 6-week dietary 27 treatment period. This research may have clinical practice and policy implications by informing U.S. 28 dietary guidelines and guidelines for T2D prevention, which devote minimal attention to NNS and 29 provide unclear guidance on NNS use due largely to a lack of rigorously-designed controlled feeding 30 trials.