Non-Nutritive Sweetener Consumption and Glucose Homeostasis in Middle-Aged and Older Adults with Prediabetes

项目摘要 观察性研究已经将非营养性甜味剂(NNS)的摄入联系在一起，这些甜味剂是 每天大约50%的中老年美国成年人，2型糖尿病(T2D)的风险增加。这一风险 可能会因年龄增加而加剧，这与低度慢性炎症和 T2D的风险增加。目前与NNS使用相关的T2D预防建议尚不清楚 而且令人困惑；建议将其用作添加糖摄入量的替代品，但长期使用NNS是 尽管只有很少的研究支持这一建议，但仍令人沮丧。动物学和观察学 人体研究表明，某些NNS对血糖稳态有不利影响。更长期的人类 研究在很大程度上证明了无效的发现。研究设计的差异和现有研究缺乏严谨性 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 NN的类型在其吸收和新陈代谢方面有所不同(例如，两种最常消耗的NN， 三氯蔗糖和阿斯巴甜)。NNS摄入量是否影响中期血糖动态平衡 老年/老年糖尿病前期患者尚不清楚，以及可能发生这种情况的潜在机制 都还没有确定。此R21提案的总体目标是为以下项目建立概念验证 摄入三氯蔗糖后血糖稳态的变化，但不是阿斯巴甜。 患有糖尿病前期的老年人与没有NNS的无糖饮食进行比较。我们会调查的 炎症标志物的变化是三氯蔗糖摄入影响的潜在机制 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) 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 每组参与者)：三氯蔗糖、阿斯巴甜或对照组(不含NNS)。标准化饮食将是 匹配大量营养素(50%碳水化合物、35%脂肪、15%蛋白质)和其他变量以避免 可能影响研究结果的体重变化和饮食因素的潜在混淆 (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 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 通过静脉葡萄糖耐量试验(IVGTT)、血清内毒素和炎症反应实现β细胞功能 包括C-反应蛋白在内的细胞因子将在6周饮食前后进行检测 治疗期。这项研究可能会有临床实践和政策影响，因为它告诉美国。 饮食指南和T2D预防指南，对NNS和 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受控喂养 审判。

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