SUN-572 Microscale Magnetic Resonance Profiling Of Plasma Oxidative Stress (os) Reveals Early Metabolic Dysfunction In Normoglycemic And Prediabetic Individuals

Abstract Disclosure: R. Rohr: ; LarmorBIO. A.T. Alves: ; LarmorBIO. B.O. Boehm: None. M.J. Mcphaul, MD: ; LarmorBIO. M. Marcelli: None. From early metabolic dysregulation to established disease, oxidative stress (OS) plays a crucial role in the pathogenesis of cardiometabolic diseases; however, existing OS biomarkers lack the sensitivity and specificity required for routine clinical use. Previously, 2D microscale magnetic resonance was used in conjunction with glycemic levels to stratify individuals with type 2 diabetes (T2D) (Peng WK, 2020), and importantly, it is a responsive biomarker to GLP-1 therapeutics (Alves, 2024). In the present study, we have used 2D microscale magnetic resonance platform to profile plasma OS in relation to metabolic health status. We profiled OS in EDTA plasma specimens in a convenience sample of 46 apparently normal non-diabetic men. Lab testing was used to identify metabolically healthy (MH) individuals (N = 9; HbA1c <5.7%, IRRS < 12%, CRP <1 mg/L). The metabolically unhealthy (MU) group (N=37) included those with one or more abnormal measurements: HbA1c >=5.7, IRRS >= 12; CRP >=1.MH group (n=9) median characteristics: age 27.7 years, BMI 22.6, HbA1c 5.3%, insulin 3.6 uIU/mL, C-peptide 1.09 ng/mL, IRRS 4.8%, hsCRP 0.4 mg/L. The MU group (N=37) exhibited varying metabolic abnormalities; median group characteristics were as follows: age 40.6 years, BMI 29.5, HbA1c 5.6%, insulin 10.6 uIU/mL, C-peptide 1.83 ng/mL, IRRS 38%, hsCRP 2.36 mg/L. Seventeen MU individuals were prediabetic.OS was significantly elevated in MU individuals: 2.41 ± 0.12 vs 2.29 ± 0.04in the MH group (p = 0.005, t-test). Prediabetic individuals (n = 17) had OS of 2.44 ± 0.14, significantly higher than MH individuals (p = 0.003, t-test). Among individuals with HbA1c < 5.7% and BMI > 25 (n = 17), OS was 2.39 ± 0.12, significantly higher than in the MH group (p = 0.005), despite all having normal HbA1c. When stratified by OS thresholds, IRRS differed significantly across groups (p = 0.0332, ANOVA), as did hsCRP (p = 0.0436, ANOVA).OS is a sensitive early indicator of metabolic dysfunction and stratifies risk within normoglycemic, overweight, and non-diabetic populations with varying levels of insulin resistance. Given that new, universally accepted, sensitive, and cost-effective blood tests defining the transition from healthy metabolic status to prediabetes are urgently required, OS may offer a novel early-stage screening marker to provide additional personalized information and guiding prevention, treatment, and long-term follow-up. Presentation: Sunday, July 13, 2025