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

患有糖尿病前期的老年人的糖精和安赛蜜的消耗量与血糖稳态

• 批准号: 10571965
• 负责人: Valisa Hedrick
• 金额: $ 24万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571965
• 关键词: Address; Adult; Aging; Animal Experimentation; Animals; Attention; Behavior; Beta Cell; Beverages; Body Weight; Body Weight Changes; C-reactive protein; CCL2 gene; Carbohydrates; Cell physiology; Chronic; Clinical; Confusion; Consumption; Continuous Glucose Monitor; Control Groups; Development; Diabetes prevention; Diet; Dietary Factors; Dietary Intervention; Elderly; Endotoxins; Fatty acid glycerol esters; Future; Guidelines; Health; Health Personnel; Human; Impairment; Inflammation; Inflammatory; Intake; Interleukin-6; Intervention Studies; Intestinal permeability; Investigation; Lead; Link; Macronutrients Nutrition; Measurement; Measures; Metabolism; Methodology; Non-Insulin-Dependent Diabetes Mellitus; Nutritional Study; Observation in research; Observational Study; Older Population; Oral; Outcome; Outcome Study; Participant; Phase; Population; Potassium; Prediabetes syndrome; Prevention Guidelines; Proteins; Public Health; Randomized; Recommendation; Reporting; Research; Research Design; Risk; Risk Reduction; Saccharin; Serum; Standardization; Strategic Planning; Sweetening Agents; TNF gene; Taste Buds; United States National Institutes of Health; absorption; aged; blood glucose regulation; capsule; clinical practice; cytokine; design; diabetes risk; dietary; dietary guidelines; evidence base; feeding; glycemic control; high risk; inflammatory marker; innovation; insight; insulin sensitivity; intravenous glucose tolerance test; middle age; policy implication; success; sugar; sweet taste perception; treatment duration; treatment guidelines; trial design

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.

1个项目摘要 2观察性研究已将消耗的非脱糖甜味剂（NNS）摄入 每天约50％的中年/年龄较大的美国成年人每天3次，2型糖尿病风险增加（T2D）。这个风险 4可能会因年龄增长而加剧，这与低度慢性炎症和 5增加T2D的风险。与NNS使用相关的当前T2D预防建议尚不清楚 6，令人困惑；建议用作添加糖摄入量的替代方法，但长期使用的使用是 7尽管研究很少，但仍劝阻这一建议。动物和观察 8人类研究表明，某些NNS对葡萄糖稳态的有害影响。长期人类 9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的缺乏严格性 10研究有助于确定的发现。此外，NNS经常被研究为一个实体 11种NN类型的吸收和代谢各不相同（例如，两种通常消耗的NNS，糖精 12和Acesulfame钾[ACE-K]）。 NNS消耗是否影响葡萄糖稳态 13个患有糖尿病前期的中年/老年人尚不清楚，并且可以通过这种机制 14尚未确定。该R21提案的总体目标是建立证明 15摄入糖精后葡萄糖稳态的改变，而不是ACE-K的概念 与没有NNS的欧加利亚饮食相比，16名年龄/老年人患有糖尿病前期。我们将调查 17炎症标记的变化是糖精摄入量影响的潜在机制 18葡萄糖稳态。遵循2周的桉树饮食，51名中年/老年人（50岁以上） 19具有糖尿病前期将随机分配到3个受控喂养条件中的1个6周（17 每组20名参与者）：糖精，ACE-K或对照组（无NNS）。标准化饮食将是 21种匹配大量营养素（50％碳水化合物，35％脂肪，15％蛋白质）和其他变量以避免 22体重变化和饮食因素的潜在混杂，可能影响研究结果 23（例如，添加的糖）。除两者的额外NN以外，所有小组都将获得相同的饮食 24个NNS组。使用连续的葡萄糖监测和胰岛素敏感性，24小时血糖控制 25通过静脉葡萄糖耐量测试（IVGTT），血清内毒素和炎症的25β细胞功能 在6周饮食之前和之后，将测量26个细胞因子，包括C反应蛋白 27治疗期。这项研究可能通过通知美国具有临床实践和政策影响 28 T2D预防的饮食指南和指南，这些指南对NNS和NNS和 29在很大程度上缺乏严格设计的受控喂养方面，提供了有关NNS使用的不明确指南 30次试验。