Association Between Glycemic Variability and Bone Turnover and the Sema3A Signaling Pathway in Postmenopausal Women with Type 2 Diabetes Mellitus

Background: This study evaluated relationships between glycemic variability, bone turnover markers, Sema3A pathway components, and bone mineral density in postmenopausal women with type 2 diabetes mellitus (T2DM). Methods: In this single-center cross-sectional study with prospective data collection, 126 postmenopausal women with T2DM performed capillary glucose measurements eight times daily for five days. Mean glucose, SD, CV, Δ glucose, and postprandial increment were calculated. Serum P1NP, CTX-1, SEMA3A, NRP1, and PLXNA1 were measured by ELISA, and P1NP/CTX-1, NRP1/PLXNA1, and SEMA3A/NRP1 ratios were derived. Bone mineral density was assessed by DXA. Associations were examined using Spearman correlation and multivariate regression adjusted for age, BMI, diabetes duration, vitamin D, PTH, insulin use, mean glucose, CV, and Δ glucose. Results: Bone turnover markers, Sema3A components, ratios, and T-scores did not differ across HbA1c-based groups (all p > 0.05). SD, CV, and Δ glucose correlated with several markers and ratios. CV was independently associated with P1NP/CTX-1 (B = −0.00174, p = 0.017); Δ glucose with NRP1 (B = −0.205, p = 0.013) and NRP1/PLXNA1 (B = −0.00023, p = 0.005); and both Δ glucose (B = 0.00035, p < 0.001) and mean glucose (B = −0.00022, p = 0.021) with SEMA3A/NRP1. Conclusions: Short-term glycemic variability, especially Δ glucose, was associated with bone turnover measures and exploratory Sema3A-related biomarkers independently of average glycemia; these associations may warrant consideration in future longitudinal studies of bone health in postmenopausal women with T2DM.