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

摘要 该项目旨在确定更换含低卡路里甜味剂的饮料(以下简称 LCSB)加无糖无糖水或苏打水可改善血糖变异性(在目标范围内的时间)并降低 1型糖尿病(T1D)儿童的内脏肥胖和全身炎症。而LCSB广泛应用于 在患有T1D的年轻人中摄入，它们在心脏代谢健康中的作用存在争议。报告LCS消耗量 促进啮齿动物和人类的葡萄糖耐量，以及人骨髓间充质干细胞的培养 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。这是令人担忧的，因为炎症和高血糖促使 患有T1D的年轻人的早期心血管疾病(CVD)与LCS摄入量、 在没有糖尿病的成年人的观察分析中，心血管疾病和中风的报告是一致的。这些发现 尤其是T1D患者，他们已经在努力控制血糖，并处于 心脏代谢风险增加。为了解决这些结果，我们计划进行一项双臂随机试验 替代常规三氯蔗糖或阿斯巴甜+安赛蜜-钾效果的对照试验 含LCSB消费量(儿童摄入的大部分LCSB含有三氯蔗糖或 阿斯巴甜+Ace-K)加不加糖的蒸馏水或苏打水12周(称为LCSB限制) 60名6-12岁儿童的血糖变异性、内脏肥胖和全身炎症 T1D。我们还将审查拟议干预措施的可行性和可接受性，并监督遵守情况。 使用自我报告和目标(尿三氯蔗糖和安赛蜜-钾)措施。失明的 连续血糖监测(CGM)、核磁共振和血液分析将在基线时进行，之后 参与者将被随机分为限制LCSB组和继续常规LCSB组(对照组)。 两组的参与者都将被指示完成照片辅助的在线三天食物记录，以及 在第1周、第6周和第12周期间，父母的帮助。所有参与者和他们的父母将收到关于 如何完成照片辅助的食物记录、持续血糖监测(CGM)的教育以及 关于一般健康饮食策略的咨询。干预组的人将获得额外的 关于如何避免LCSB的指导。随访时将再次进行CGM、血液分析和MRI检查。如果 限制LCSB可改善血糖变异性，降低内脏脂肪和全身炎症，这些 研究结果将有助于开展一项更大规模和更长期的试验，以阐明LCS的潜在机制 并将证明或挑战在患有T1D的儿童中鼓励LCSB的标准做法。

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.