Abstract

Background: Insulin resistance plays a central role in the pathophysiology of T2DM and may critically influence bone metabolism. This study aimed to explore the comparative levels of insulin resistance with Meta inflammatory and bone turnover markers in type 2 diabetic women with osteoporosis. Methods: In a cross-sectional study, 50 women with T2DM and osteoporosis and 40 healthy controls, aged 45 to 75 years, were evaluated for bone turnover markers using dual‑energy X‑ray absorptiometry (DXA) scans at the spine and hip. T‑score of ≤−2.5 was defined as osteoporosis, and score −2.49 to −1.0 as osteopenia at either site. Correlation of Insulin resistance with inflammatory cytokines, Wnt pathway inhibitors, bone turnover markers, minerals, and vitamin D was evaluated. Diagnostic performance was assessed using ROC curve analysis. Results: Non-significant changes (p>0.05) were seen in the level of BMI. HOMA-IR, Insulin, HbA1c, TNF-α, IL-6, ALP, DKK1, SOST, CTSK, and PTH were significantly increased (p<0.01), while vit. D, Osteocalcin, Ca, Phosphorus, Mg, and T-score were significantly decreased (p<0.01) in patients with T2DM and osteoporosis, compared to controls. The HOMA-IR displayed excellent diagnostic accuracy and correlated with inflammatory markers (TNF-α and IL-6), Wnt signaling inhibitors (DKK-1 and sclerostin), changes in bone turnover markers and disturbed mineral homeostasis. This link points to insulin resistance as an integral link between metabolic derangement and skeletal fragility. Insulin resistance is a key central pathophysiological link between metabolic dysregulation, chronic inflammation, impeded bone remodeling and osteoporosis in T2DM.  Integrating insulin resistance assessment with bone-related biomarkers may enhance early diagnosis and risk stratification.