Trabecular bone score differs among prediabetes phenotypes: the potential mediating role of visceral adiposity

Prediabetes comprises heterogeneous metabolic phenotypes that may differentially affect bone quality. While type 2 diabetes increases fracture risk despite preserved bone mineral density, phenotype-specific effects on bone quality during prediabetes remain unclear. We compared trabecular bone score (TBS) across prediabetes phenotypes and examined visceral adiposity's mediating role.

We analyzed 876 individuals with prediabetes (451 men, 425 postmenopausal women) from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort. Participants underwent oral glucose tolerance testing for phenotype classification (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], combined IFG+IGT) and dual-energy X-ray absorptiometry for TBS and body composition. Bootstrap mediation analysis (5,000 iterations) tested whether visceral adipose tissue (VAT) accounted for phenotype-TBS associations.

Prediabetes phenotypes showed distinct, sex-specific patterns of bone quality impairment linked to visceral fat. In men, IGT had the lowest TBS (1.46 ± 0.09) compared with IFG (1.49 ± 0.08) and IFG+IGT (1.48 ± 0.07, both p < 0.05). In women, IFG+IGT had the lowest TBS (1.42 ± 0.08) versus IFG (1.44 ± 0.07, p < 0.05). VAT paralleled these TBS patterns and mediated 51% (95% CI 28-74%) of the IGT effect in men and 26% (95% CI 8-45%) of the IFG+IGT effect in women.

Prediabetes phenotypes are associated with distinct TBS patterns-IGT in men and IFG+IGT in women showing the lowest values. Visceral adiposity mediated approximately half of the association in men with IGT, suggesting sex- and phenotype-specific pathways linking prediabetes to bone microarchitecture.