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.
Consumption of beverages containing low-calorie sweeteners (LCSB) is often encouraged among youth with type 1 diabetes (T1D) as part of diabetes management, yet effects of LCSB on cardiometabolic health are controversial. While use of LCS in place of added sugars reduces the calorie and sugar content of beverages, this replacement may paradoxically worsen glycemic control and exacerbate cardiometabolic health among already at-risk children with T1D. The proposed project will examine effects of replacement of usual LCSB consumption with unsweetened still or seltzer water for 12 weeks on glycemic variability (time in target range) and biomarkers of cardiometabolic health in children with T1D.
