Diabetic Peripheral Neuropathy With Low Appendicular Muscle Mass Is Associated With Osteoporosis, Falls, and Fractures

INTRODUCTION: Diabetic peripheral neuropathy (DPN) and low appendicular muscle mass (LAMM) may jointly contribute to adverse skeletal outcomes, but their combined effects remain unclear. We examined their associations with osteoporosis, falls, and fractures in patients with Type 2 diabetes. METHODS: We explored associations of diabetes and grip strength with skeletal outcomes using SHARE v8.0.0 (327 248 participants). The primary analysis used a cohort of patients with Type 2 diabetes from the First Affiliated Hospital of Fujian Medical University. LAMM was defined using dual-energy X-ray absorptiometry-derived appendicular skeletal muscle mass index. Associations of clinically diagnosed DPN, LAMM, and their coexistence with osteoporosis, falls, and fractures were evaluated using logistic regression and Cox survival models. Exploratory serum antibody omics was performed. RESULTS: In SHARE, grip strength was inversely associated with all three outcomes. In the local cohort, coexisting DPN and LAMM were associated with higher odds of osteoporosis (OR 2.151, 95% CI 1.645-2.805), falls (OR 4.667, 95% CI 3.406-6.376), and fractures (OR 2.416, 95% CI 1.367-3.515; all p < 0.001). Cox analyses showed higher hazards of osteoporosis (HR 3.410, 95% CI 1.579-7.362; p = 0.002) and falls (HR 4.385, 95% CI 1.838-10.459; p < 0.001), but not fractures (HR 0.708, 95% CI 0.187-2.675; p = 0.611). Antibody omics suggested a reactivity profile involving endoplasmic reticulum protein processing and neurodegeneration-related pathways. CONCLUSION: Coexisting DPN and LAMM were associated with higher odds of all three skeletal outcomes and higher longitudinal hazards of osteoporosis and falls, but not fractures. The exploratory omics findings require functional validation.