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

中老年人糖尿病前期的非营养性甜味剂消耗与血糖稳态

• 批准号: 10353577
• 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: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10353577
• 关键词: Address; Adult; Aging; Animal Experimentation; Animals; Aspartame; Attention; Behavior; Beta Cell; Beverages; Body Weight; Body Weight Changes; C-reactive protein; CCL2 gene; Carbohydrates; Cell physiology; Chronic; Clinical; Consumption; 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; Prediabetes syndrome; Prevention Guidelines; Proteins; Public Health; Randomized; Recommendation; Reporting; Research; Research Design; Risk; Risk Reduction; Serum; Standardization; Strategic Planning; Sweetening Agents; TNF gene; Taste Buds; United States National Institutes of Health; absorption; base; blood glucose regulation; capsule; clinical practice; cytokine; design; diabetes risk; dietary; dietary guidelines; evidence base; feeding; glucose monitor; 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

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.

项目摘要 观察性研究已将其消耗的非营养甜味剂（NNS）的摄入联系起来 每天约有50％的中年/年龄较大的美国成年人，患有2型糖尿病风险（T2D）。这个风险 可能会因年龄增长而加剧，这与低度慢性炎症和 T2D的风险增加。与NNS使用相关的当前T2D预防建议尚不清楚 和令人困惑；建议用作添加糖摄入量的替代方法，但长期使用的使用是 尽管研究很少，但仍劝阻这一建议。动物和观察 人类研究表明，某些NNS对葡萄糖稳态的影响。长期人类 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的缺乏严格性 研究有助于确定的发现。此外，NNS经常被研究为一个实体 NN的类型在吸收和代谢方面有所不同（例如，两种最常见的NNS， 三氯蔗糖和阿斯巴甜）。 NNS消费是否影响中间的葡萄糖稳态 老年/老年人患有糖尿病前期是未知的，并且可能发生这种情况的潜在机制 尚未确定。该R21提案的总体目的是为 摄入三氯蔗糖（但不是阿斯巴一种）之后葡萄糖稳态的改变，中间 与没有NNS的欧卡拉克饮食相比，年龄/老年人患有糖尿病前期。我们将调查 炎症标志物的变化是三氯蔗糖摄入影响的潜在机制 葡萄糖稳态。遵循2周的桉树饮食，51名中年/老年人（50岁以上） 糖尿病前期将随机分配到3个受控喂养条件中的1个，持续6周（17 每个组的参与者）：三氯蔗糖，阿斯巴甜或对照组（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 体重变化和饮食因素的潜在混杂，可能影响研究结果 （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 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 通过静脉葡萄糖耐受性测试（IVGTT），血清内毒素和炎症性通过β细胞功能 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。这项研究可能通过通知美国具有临床实践和政策影响 T2D预防的饮食指南和指南，这些指南将最小的关注点用于NNS和 在很大程度上缺乏严格设计的受控饲料，提供有关NNS使用的不明确指南 试验。