Effects of Low-calorie Sweetened Beverage Restriction in Youth with Type 1 Diabetes

限制低热量甜味饮料对患有 1 型糖尿病的青少年的影响

• 批准号: 9979429
• 负责人: Allison Sylvetsky
• 金额: $ 22.69万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979429
• 关键词: 12 year old; Address; Adherence; Adolescent; Adult; Age; Aspartame; Beverages; Biological Assay; Biological Markers; Blinded; Blood; Blood Glucose; Calories; Cardiovascular Diseases; Child; Childhood; Collaborations; Complications of Diabetes Mellitus; Consumption; Counseling; Crystallization; Development; Diabetes Mellitus; Disease; Dose; Education; Enrollment; Fatty acid glycerol esters; Follow-Up Studies; Food; Fruit; Genes; Glucose; Glucose Intolerance; Glucose Transporter; Glycosylated hemoglobin A; Goals; HDL-triglyceride; Hawaiian population; Health; Healthy Eating; High Prevalence; Human; Hyperglycemia; Impairment; Incidence; Inflammation; Inflammatory; Instruction; Insulin-Dependent Diabetes Mellitus; Intake; Intervention; Intervention Studies; Intervention Trial; Light; Link; Lipids; Low Prevalence; Low-Density Lipoproteins; Magnetic Resonance Imaging; Measurement; Measures; Medical center; Metabolic; Metabolic syndrome; Monitor; Mus; Obesity; Observational Study; Outcome; Parents; Participant; Patient Self-Report; Patients; Physiological; Plasma; Potassium; Prevention; Randomized; Randomized Controlled Trials; Records; Reporting; Risk; Risk Factors; Rodent; Role; Stroke; Sweetening Agents; TNF gene; Time; Triglycerides; Urine; Visceral; Vulnerable Populations; Water; Youth; absorption; arm; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; clinically relevant; cohort; diabetes management; dosage; gatorade; glucose monitor; glycemic control; group intervention; gut microbiota; improved; insulin sensitivity; patient population; programs; recruit; stem cells; sugar; sweetened beverage; trial comparing; urinary

Abstract This project aims to determine whether replacement of beverages containing low-calorie sweeteners (hereafter LCSB) with unsweetened still or seltzer water improves glycemic variability (time in target range) and reduces visceral adiposity and systemic inflammation in children with type 1 diabetes (T1D). While LCSB are widely consumed in youth with T1D, their role in cardiometabolic health is controversial. LCS consumption is reported to promote glucose intolerance in rodents and humans, and incubation of human mesenchymcal stem cells with sucralose at clinically relevant doses upregulated expression of glucose transporter genes as well as markers of fat accumulation and inflammation. This is alarming because inflammation and hyperglycemia drive early cardiovascular disease (CVD) in youth with T1D and positive associations between LCS consumption, CVD, and stroke are consistently reported in observational analyses in adults without diabetes. These findings are particularly concerning for patients with T1D, who already struggle with glycemic control and are at heightened cardiometabolic risk. To address these outcomes, we plan to conduct a two-arm randomized controlled trial comparing effects of replacement of usual sucralose or aspartame + acesulfame-potassium containing LCSB consumption (the majority of LCSB consumed by children contain either sucralose or aspartame + ace-K) with unsweetened still or seltzer water for 12 weeks (referred to as LCSB restriction) on glycemic variability, visceral adiposity, and systematic inflammation in 60 children ages 6-12 years old with T1D. We will also examine the feasibility and acceptability of the proposed intervention and monitor adherence using both self-report and objective (urinary sucralose and acesulfame-potassium) measures. Blinded continuous glucose monitoring (CGM), MRI, and blood assays will be performed at baseline, after which participants will be randomized to either LCSB restriction or continuation of usual LCSB intake (control). Participants in both groups will be instructed to complete photo-assisted, online, three day food records, with the help of their parents, during weeks 1, 6, and 12. All participants and their parent will receive instructions on how to complete photo-assisted food records, education on continuous glucose monitoring (CGM), and counseling on general healthy eating strategies. Those in the intervention group will receive additional guidance on how to avoid LCSB. CGM, blood assays and MRI will be performed again at study follow up. If LCSB restriction improves glycemic variability and lowers visceral adiposity and systemic inflammation, these findings will inform the development of a larger and longer-term trial to elucidate mechanisms underlying LCS effects and will justify or challenge the standard practice of encouraging LCSB among children with T1D.

摘要 本项目旨在确定是否可以替代含有低热量甜味剂的饮料（以下简称 LCSB）与不加糖的蒸馏水或苏打水混合使用，可改善血糖变异性（目标范围内的时间）， 1型糖尿病（T1 D）儿童的内脏肥胖和全身炎症。虽然LCSB广泛 在患有T1 D的年轻人中，它们在心脏代谢健康中的作用是有争议的。报告LCS消耗 促进啮齿动物和人类的葡萄糖耐受不良，以及人类间充质干细胞的孵育 临床相关剂量的三氯蔗糖上调葡萄糖转运蛋白基因的表达， 脂肪堆积和炎症的标志物。这是令人担忧的，因为炎症和高血糖会导致 T1 D青年的早期心血管疾病（CVD）与LCS消耗之间的正相关， 在无糖尿病成人的观察性分析中，CVD和卒中的报告一致。这些发现 对于T1 D患者来说尤其令人担忧，他们已经在努力控制血糖， 心脏代谢风险增加为了解决这些结果，我们计划进行双臂随机化 对照试验，比较替代常用三氯蔗糖或双甘氨+乙酰磺胺酸钾的效果 含有LCSB的消费（儿童消费的大多数LCSB含有三氯蔗糖或 阿糖胞苷+ ace-K）与不加糖的蒸馏水或苏打水共12周（称为LCSB限制）， 60名6-12岁儿童的血糖变异性、内脏肥胖和系统性炎症， T1 D。我们亦会研究建议的干预措施的可行性和可接受性，并监察有关措施的执行情况 使用自我报告和客观（尿三氯蔗糖和安赛蜜-钾）测量。盲 将在基线时进行连续葡萄糖监测（CGM）、MRI和血液分析，之后 将参与者随机分配至LCSB限制或继续常规LCSB摄入（对照）。 两组的参与者将被指示完成照片辅助的在线三天食物记录， 在父母的帮助下，在第1周，第6周和第12周。所有参与者及其家长将收到以下指示 如何完成照片辅助的食物记录，持续葡萄糖监测（CGM）的教育，以及 提供一般健康饮食策略的咨询。干预组的人将获得额外的 指导如何避免LCSB。研究随访时将再次进行CGM、血液分析和MRI。如果 LCSB限制改善血糖变异性，降低内脏肥胖和全身炎症，这些 这些发现将为更大规模和更长期的试验提供信息，以阐明LCS的潜在机制 影响，并将证明或挑战鼓励T1 D儿童LCSB的标准做法。