GLOW UP Study: Protocol for an Observational Digital Biomarker Study for Prediabetes Screening and Digital Phenotyping

IntroductionPrediabetes, a key precursor to type 2 diabetes, is highly prevalent and underdiagnosed, particularly among adults aged [≥]45 years with elevated body mass index (BMI). Early detection is critical because lifestyle interventions can delay or prevent progression to type 2 diabetes. The Glow Up (GLucose Observation and Wearable Use for Prevention) study aims to (1) test the feasibility of a digital biomarker for prediabetes screening using wearable- and smartphone-derived lifestyle factors (e.g., sleep, physical activity, and nutrition patterns), in daily life and to (2) characterize individual- and metabolic subgroup-level variability in lifestyle factors and glycemic control. Specifically, we aim to examine how lifestyle factors relate to diabetes risk and identify personalized predictors of early metabolic dysregulation. Methods and analysisGlow Up is a prospective, single-center, observational case-control study conducted in Switzerland. Adults (N=200) aged [≥]45 years with BMI [≥]25 kg/m{superscript 2} will be recruited, including n=100 individuals with prediabetes and n=100 age- and sex-matched case-control normoglycemic controls. Participants will undergo four weeks of continuous monitoring using a blinded continuous glucose monitor (CGM), and commercial- and medical-grade wearables; e.g. capturing physical activity, sleep, and physiological markers (heart rate variability, heart rate and skin temperature); in addition to completing daily image-based meal logs, using smartphones. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and body anthropometrics will be collected at baseline and follow-up, four weeks apart. Primary outcomes include HbA1c and FPG, measured at approximately four week follow-up. Secondary outcomes include CGM metrics, lifestyle profiling (sleep, physical activity, stress, and nutrition), and adherence to image-based meal logging. Ethics and disseminationThe study has received ethics approval from the Ethics Committee of Eastern Switzerland (BASEC ID.: 2025-00972). Results will be published in international peer-reviewed journals and at national and international conferences as posters, presentations, and articles. Summaries will be provided to the funders and personalized reports to participants. Trial registration numberNCT07373418 Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIGlow Up presents the first study in Switzerland to investigate glycaemic and lifestyle profiling among individuals with normoglycaemia and prediabetes in an observational, free-living setting. C_LIO_LITo our knowledge, Glow Up is the first dataset to combine continuous glucose monitoring, commercial- and medical-grade wearable sensors, smartphone-based questionnaires, image-based dietary logging under free-living conditions, and clinical biomarkers, HbA1c and FPG; allowing for rich digital phenotyping. C_LIO_LIInclusion of baseline and follow-up clinical biomarkers (HbA1c and FPG) provides clinically validated ground truth measures, strengthening outcome validity and anchoring digital and wearable-derived markers to established clinical, diagnostic standards. C_LIO_LIThe absence of direct measures of insulin resistance, lipid metabolism, and gut microbiome compositions may limit more mechanistic investigation of glucose dysregulation patterns and metabolic sub phenotyping. C_LIO_LIThe four-week follow-up period may limit inference on longer-term glycaemic trajectories and progression to T2D. C_LIO_LIFindings may not be generalisable beyond at-risk adults living in Switzerland who meet the study eligibility criteria. C_LI