Association of Glycemic Status with Disability, Relapse Activity, Inflammatory Markers, and Metabolic Profile in...

Background/Objectives: Metabolic dysregulation has emerged as a potential modifier of disease activity and disability in multiple sclerosis (MS). However, the relationship between glycemic status and clinical outcomes in patients with MS remains incompletely understood. This study aimed to investigate the associations of glycemic regulation with disease severity, relapse activity, inflammatory markers, and metabolic characteristics in patients with MS. Methods: In this retrospective single-center observational study, 455 patients with MS aged 18-65 years were included. Patients were categorized into normoglycemia (n = 241), prediabetes (n = 98), and diabetes (n = 116) according to American Diabetes Association criteria and documented diabetes diagnosis. Demographic characteristics, Expanded Disability Status Scale (EDSS) scores, annualized relapse rate (ARR), disease-modifying therapy (DMT), hematological indices, inflammatory markers, and metabolic parameters were retrieved from electronic medical records. Associations between glycemic status and clinical outcomes were evaluated using group comparisons, Spearman correlation analyses, and multivariable linear regression models. Results: Significant differences were observed among glycemic groups for age, disease duration, EDSS score, ARR, MS phenotype, platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipid parameters, estimated glomerular filtration rate, alanine aminotransferase, gamma-glutamyl transferase, triglyceride-glucose (TyG) index, and atherogenic index of plasma (all p < 0.05). HbA1c, FPG, TyG index, lipid parameters, CRP, and ESR were positively correlated with EDSS scores (all p < 0.05). In contrast, these markers showed inverse correlations with ARR. However, after adjustment for demographic and clinical variables, including age, sex, disease duration, MS phenotype, and disease-modifying therapy (DMT), neither prediabetes nor diabetes remained independently associated with disability, as measured by the EDSS score, or with ARR. Progressive MS phenotype, older age, and longer disease duration were independently associated with higher disability, whereas age, disease duration, and progressive phenotype were independently associated with lower ARR. Conclusions: Impaired glycemic status is associated with greater disability, unfavorable metabolic profiles, and increased systemic inflammation in patients with MS. Nevertheless, glycemic status was not independently associated with disability or relapse activity after adjustment for major clinical confounders. These findings suggest that metabolic dysregulation accompanies more severe clinical characteristics but may not independently drive disease progression in MS.