Glycemic Impact of NNS Via the Gut Microbiome

This pilot study will evaluate the feasibility and acceptability of a 30-day sucralose intervention among adults with prediabetes. Participants will consume six commercial sucralose (Splenda®) packets daily for 30 days while wearing a blinded continuous glucose monitor (CGM). Oral glucose tolerance tests (OGTTs) with blood draws will be performed at baseline and after 30 days to assess glucose incremental area under the curve (iAUC). Stool samples will also be collected to assess the feasibility of microbiome sample collection for future studies. The study will generate preliminary data to inform the design of a larger randomized clinical trial examining the effects of non-nutritive sweeteners on glucose homeostasis and the gut microbiome.

Inclusion Criteria: * HbA1c measured within the past 6 months between 5.7% and 6.4%. * eGFR measured within the past 6 months of at least 45 mL/min/1.73 m². * Prediabetes defined by diagnosis code R73.0 or a subcategory. * Age 35 years or older. * BMI of at least 25 kg/m². * Low non-nutritive sweetener use, defined as less than once per week. Exclusion Criteria: * Type 1 diabetes. * Type 2 diabetes. * History of bariatric surgery. * History of organ or tissue transplantation. * Current GLP-1 agonist treatment. * Current metformin treatment. * Current oral steroid medication. * Current immunosuppressant use, including tacrolimus, cyclosporine, mycophenolate mofetil, prednisone, methylprednisolone, sirolimus, or everolimus. * Severe gastrointestinal disease, at the discretion of the PI and physician Co-Investigator. * Severe comorbidities with poor physical or mental function that may prevent completion of study procedures, at the discretion of the PI and physician Co-Investigator. * Current or planned pregnancy or lactation. * Self-reported non-nutritive sweetener allergy or intolerance. * Regular consumption of non-nutritive sweetener products, defined as once per week or more often. * Concurrent participation in another study involving dietary changes, investigational drugs, or microbiome-altering agents.