Cluster-derived immunometabolic profiles: association with glycemic dysregulation in elderly postmenopausal women

Abstract Purpose To identify variations in immunometabolic profiles in elderly postmenopausal women using a data-driven clustering approach and to examine differences in insulin resistance (HOMA-IR) and glycemic control (HbA1c) across the derived profiles. Methods This cross-sectional study included 132 women with a mean age of 70.8 years. Unsupervised hierarchical cluster analysis (Ward.D2 method, squared Euclidean distance) was performed using twelve variables spanning demographic, hemodynamic, metabolic, inflammatory, and vitamin D-related domains. HbA1c and HOMA-IR were compared across clusters; HOMA-IR was not fully independent of cluster derivation because fasting glucose contributes to its calculation. Between-cluster differences were assessed using Kruskal–Wallis tests or one-way ANOVA. DSCF post-hoc tests and epsilon-squared (ε²) effect sizes were used for non-parametric comparisons. Results Three cluster-derived profiles were identified (Cluster 1, n = 25; Cluster 2, n = 50; Cluster 3, n = 57). Cluster 1 was characterized by lower IL-10 levels and a less favorable lipid profile, while blood pressure was similarly elevated in Clusters 1 and 2 relative to Cluster 3. Cluster 2 showed an overall intermediate profile, with the lowest vitamin D concentration as its most distinctive feature. Cluster 3 exhibited lower blood pressure, higher IL-10 levels, and a more favorable lipid profile. When examining these additional glycemic measures, HbA1c showed a graded increase across clusters ( p < 0.05 for all pairwise comparisons), whereas HOMA-IR differed between Cluster 3 and Clusters 1 and 2 but did not differ significantly between Clusters 1 and 2. Conclusion The differentiation of elderly postmenopausal women into three data-driven immunometabolic profiles illustrated substantial heterogeneity. These findings suggest that HbA1c may provide complementary information to fasting-based indices when characterizing immunometabolic heterogeneity in elderly postmenopausal women.