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

项目摘要 观察性研究表明，非营养性甜味剂（NNS）的摄入与 约50%的中年/老年美国成年人每天服用，2型糖尿病（T2 D）的风险增加。这种风险 可能会因年龄增长而加剧，这与低度慢性炎症有关， 增加T2 D的风险。目前与NNS使用相关的T2 D预防建议尚不清楚 和混淆;建议使用作为添加糖摄入量的替代品，但长期使用NNS是 尽管很少有研究支持这一建议，但仍感到沮丧。动物和观察 人体研究表明某些NNS对葡萄糖稳态有有害作用。长期人类 研究基本上证明没有结果。研究设计的差异和现有研究缺乏严谨性 研究有助于不确定的结果。此外，NNS通常作为一个单一的实体进行研究， NNS的类型在它们的吸收和代谢方面不同（例如，两种最常食用的NNS， 三氯蔗糖和双甘氨酯）。NNS的消耗是否会影响中- 老年人/老年人糖尿病前期是未知的，其可能发生的潜在机制 还有待确认本R21提案的总体目标是建立以下概念验证： 摄入三氯蔗糖后葡萄糖稳态的改变，但不包括果糖，在中期- 老年/老年糖尿病前期患者与无NNS的正常热量饮食相比。我们将调查 炎症标志物的变化作为三氯蔗糖摄入影响 葡萄糖稳态在2周的正常热量饮食后，51名中年/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1种，持续6周（17 参与者/组）：三氯蔗糖、美罗华或对照组（无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 (e.g.,添加的糖）。所有组将接受相同的饮食，除了两个额外的NNS NNS集团。使用连续血糖监测和胰岛素敏感性进行24小时血糖控制， 通过静脉内葡萄糖耐量试验（IVGTT）、血清内毒素和炎性 细胞因子，包括C-反应蛋白，将在6周饮食之前和之后测量。 治疗期。这项研究可能具有临床实践和政策意义，通过告知美国。 饮食指南和T2 D预防指南，对NNS的关注最少， 由于缺乏严格设计的控制喂养，NNS使用指南不明确 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.