Waist-to-Body Mass Index Ratio and Risk of Musculoskeletal Disease in Type 2 Diabetes: A Cohort and PhIP-Seq Analysis

Musculoskeletal complications in type 2 diabetes (T2DM) are inadequately captured by body mass index (BMI). Waist-to-BMI ratio (WBR) may better reflect adverse body composition. We examined cross-sectional and longitudinal associations between WBR and musculoskeletal disorders in T2DM.

This two-phase study was conducted within an ongoing hospital-based cohort at the First Affiliated Hospital of Fujian Medical University (Fuzhou, China). The cross-sectional analysis included 4157 adults with T2DM recruited between March 2012 and August 2023 (54.3% men; mean age 59.4 ± 10.3 years), using data from their first assessment. Associations of waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), BMI and WBR with osteopenia, sarcopenia, sarcopenic osteopenia (SOs), sarcopenic obesity (SOb) and fractures were evaluated. The prospective cohort comprised a longitudinal subset enrolled between March 2012 and June 2022, ensuring at least 1 year of follow-up prior to administrative censoring in August 2023. A total of 440 individuals (57.0% men; mean age 59.7 ± 9.7 years) were followed for a median of 34.0 months (20.0-57.0). Associations between time-dependent WBR and incident outcomes were assessed using Cox models. A nested exploratory analysis was conducted within the cohort. Thirty participants with extreme annualised WBR change (ΔWBR/yr) were selected. Baseline serum samples collected at enrolment, prior to outcome occurrence, were analysed using phage immunoprecipitation sequencing (PhIP-Seq).

Cross-sectionally, WBR was negatively correlated with bone mineral density and appendicular skeletal muscle mass index and positively correlated with osteopenia, sarcopenia, SOs, SOb and fractures (all p < 0.01), whereas BMI, WC, WHtR and WHR showed weaker associations. After adjustment, higher WBR was independently associated with osteopenia (men: OR 1.723, 95% CI 1.614-1.840; women: OR 1.420, 1.348-1.495), sarcopenia (men: OR 4.779, 4.165-5.484; women: OR 2.991, 2.683-3.334), SOs (men: OR 6.261, 5.314-7.377; women: OR 4.336, 3.753-5.010), SOb (men: OR 4.737, 3.975-5.646; women: OR 4.652, 3.715-5.825) and fractures (men: OR 1.236, 1.093-1.397; women: OR 1.103, 1.003-1.213; all p < 0.05). Prospectively, higher time-dependent WBR predicted incident osteopenia (HR 1.365, 95% CI 1.024-1.820), sarcopenia (HR 1.282, 1.086-1.512), SOs (HR 1.408, 1.176-1.686), SOb (HR 1.634, 1.262-2.116) and fractures (HR 1.369, 1.029-1.821). PhIP-Seq analysis identified differential autoantibody reactivity related to muscle structural organisation and cytoskeletal regulation, while bone-related differences were enriched in Wnt signalling and hormone-related pathways.

Higher WBR and longitudinal increases were independently associated with osteopenia, sarcopenia, sarcopenic phenotypes and fractures in individuals with T2DM.