Neuropathy, Low Muscle Mass Linked to Falls in Type 2 Diabetes

Key Takeaways

• Among patients with type 2 diabetes in a local cohort at the First Affiliated Hospital of Fujian Medical University, China, coexisting DPN and LAMM were associated with higher odds of osteoporosis, falls, and fractures.
• Coexisting DPN and LAMM were associated with significantly higher longitudinal hazards of osteoporosis and falls, but not a significantly higher fracture hazard.
• Greater grip strength was inversely associated with osteoporosis, falls, and fractures in the separate SHARE analysis.

Diabetic peripheral neuropathy and reduced appendicular muscle mass can coexist in people with type 2 diabetes. Osteoporosis, falls, and fractures are distinct outcomes, and an association with one need not extend to the others over time. For patients with both conditions, whether these outcomes track together over time remains uncertain.

Investigators conducting a study of neuropathy, low appendicular muscle mass, and skeletal outcomes based their primary analysis on patients with type 2 diabetes at the First Affiliated Hospital of Fujian Medical University in China. Diabetic peripheral neuropathy (DPN) was clinically diagnosed; low appendicular muscle mass (LAMM) was defined using appendicular skeletal muscle mass index derived from dual-energy X-ray absorptiometry (DXA). Logistic regression assessed odds, while Cox survival models assessed hazards of osteoporosis, falls, and fractures in relation to DPN, LAMM, and their coexistence. Separately, investigators analyzed diabetes, grip strength, and skeletal outcomes in the Survey of Health, Ageing and Retirement in Europe (SHARE) v8.0.0 dataset of 327 248 participants. They also performed exploratory serum antibody omics.

In the local type 2 diabetes cohort, coexisting DPN and LAMM were significantly associated with higher odds of osteoporosis, falls, and fractures. For falls, the odds ratio (OR) was 4.667, with a 95% confidence interval (CI) of 3.406-6.376; for fractures, the OR was 2.416. These odds estimates do not describe the risk of subsequent events.

In longitudinal models, the hazard ratio (HR) for osteoporosis with coexisting DPN and LAMM was 3.410 (95% CI 1.579-7.362), and the HR for falls was 4.385. Both hazards were significantly higher, whereas the fracture hazard was not significantly higher. In the separate SHARE analysis, greater grip strength was inversely associated with osteoporosis, falls, and fractures.

These observational associations do not establish that DPN and LAMM cause osteoporosis, falls, or fractures. Higher fracture odds in the local cohort should not be interpreted as evidence of a significantly higher longitudinal fracture hazard. The authors said the exploratory serum antibody findings require functional validation before they can be treated as an explanation for the clinical associations.

According to the authors, coexisting DPN and LAMM tracked all three skeletal outcomes in odds models but only osteoporosis and falls, not fractures, in survival models.

Clinician Questions

Which pathways appeared in exploratory antibody analysis of diabetic neuropathy and low muscle mass?

Exploratory serum antibody analysis in the investigation of diabetic peripheral neuropathy and low appendicular muscle mass suggested reactivity involving endoplasmic reticulum protein processing and neurodegeneration-related pathways. This does not establish a causal pathway; the authors said functional validation was needed.