Waist circumference is an effect modifier of the association between bone mineral density and glucose metabolism

ABSTRACT Objective: The role of bone markers on insulin resistance (IR) remains controversial. The objective of this study is to evaluate the association between bone mineral density (BMD) and glucose metabolism and investigate if visceral hyperadiposity, evaluated by waist circumference (WC), is an effect modifier of this association. Subjects and methods: Cross-sectional analysis with 468 young adults from the fourth follow-up of the 1978/79 Ribeirão Preto prospective birth cohort, Brazil. BMD, total osteocalcin (OC), fasting plasma glucose and insulin concentrations were assessed. IR, sensitivity (S) and secretion (β) were estimated by homeostasis model assessment (HOMA) indexes. Multiple linear regression models were constructed to estimate the association between BMD and glucose metabolism. Beta coefficient, R2 and p-values were provided. WC was tested as an effect modifier and OC as a confounder. The covariates were selected based on Direct Acyclic Graph. Results: Significant interaction between BMD (femoral neck and proximal femur areas) and WC on glucose metabolism was observed in the adjusted models. Subjects with increased WC presented a positive association between BMD and log HOMA1-IR while an inverse association was found in those with normal WC (femoral neck R2 = 0.17, p = 0.036; proximal femur R2 = 0.16, p = 0.086). BMD was negatively associated with log HOMA2-S in individuals with increased WC and positively in those with normal WC (femoral neck R2 = 0.16, p = 0.042; proximal femur R2 = 0.15, p = 0.097). No significant associations between BMD, log HOMA2-β and OC and glucose metabolism markers were observed. Conclusions: BMD was associated with glucose metabolism, independently of OC, and WC modifies this association.

摘要
**研究目的**：骨标志物在胰岛素抵抗（insulin resistance, IR）中的作用仍存在争议。本研究旨在评估骨密度（bone mineral density, BMD）与糖代谢之间的关联，并探究通过腰围（waist circumference, WC）评估的内脏脂肪过多是否为该关联的效应修饰因子。
**研究对象与方法**：本研究基于巴西1978/1979年里贝朗普雷图前瞻性出生队列的第四次随访数据，对468名年轻成年人开展横断面分析。检测指标包括骨密度、总骨钙素（osteocalcin, OC）、空腹血浆葡萄糖及胰岛素浓度。通过稳态模型评估（homeostasis model assessment, HOMA）指数估算胰岛素抵抗、胰岛素敏感性（S）及胰岛素分泌功能（β）。构建多重线性回归模型以评估骨密度与糖代谢的关联，并报告β系数、R²及P值。以腰围作为效应修饰因子、骨钙素作为混杂因素进行分析。协变量的筛选基于有向无环图（Direct Acyclic Graph, DAG）。
**研究结果**：在校正模型中，骨密度（股骨颈及股骨近端区域）与腰围对糖代谢存在显著交互作用。在腰围升高的受试者中，骨密度与log转换的HOMA1-IR呈正相关；而在腰围正常的受试者中，二者呈负相关（股骨颈：R²=0.17，P=0.036；股骨近端：R²=0.16，P=0.086）。在腰围升高的个体中，骨密度与log转换的HOMA2-S呈负相关，而在腰围正常的个体中呈正相关（股骨颈：R²=0.16，P=0.042；股骨近端：R²=0.15，P=0.097）。未观察到骨密度、log转换的HOMA2-β及骨钙素与糖代谢标志物之间存在显著关联。
**研究结论**：骨密度与糖代谢存在关联，且不受骨钙素的影响，腰围可对该关联起到修饰作用。