Abstract
Type 2 diabetes mellitus (T2DM) frequently coexists with hyperthyroidism (HT), compounding metabolic disturbances. However, the role of specific biomarkers in this comorbid condition remains unclear. This study investigates the clinical significance of serum semaphorin 5A (Sema5A) and insulin-like growth factor-binding protein 3 (IGFBP-3) in patients with T2DM and HT, focusing on their association with glucose metabolism and diagnostic potential. A total of 191 participants were enrolled and divided into 3 groups: T2DM with HT (n = 68), T2DM only (n = 51), and healthy controls (n = 72). Clinical parameters and serum levels of Sema5A, IGFBP-3, fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), and fasting insulin were measured. Pearson correlation, logistic regression, and receiver operating characteristic curve analyses were performed to evaluate associations and diagnostic performance. Serum levels of Sema5A and IGFBP-3 were significantly elevated in the T2DM with HT group compared to other groups (P < .01). Both biomarkers showed positive correlations with fasting plasma glucose, glycated hemoglobin, HOMA-IR, and fasting insulin (P < .001). Multivariate logistic regression identified Sema5A, IGFBP-3, HOMA-IR, and thyroid autoantibodies (thyroid-stimulating hormone receptor antibody and thyroid peroxidase antibody) as independent risk factors. Receiver operating characteristic analysis demonstrated strong diagnostic value for Sema5A (area under the curve = 0.793) and IGFBP-3 (area under the curve = 0.831). Elevated Sema5A and IGFBP-3 levels are closely associated with impaired glucose metabolism in T2DM patients with HT and may serve as promising biomarkers for early diagnosis and clinical assessment of this comorbidity.