Diabetic neuropathy affects more than nerves: new evidence links muscle quality, physical performance and bone health
Aims: To investigate whether diabetic neuropathy is associated with alterations in muscle morphology, strength and physical performance in people with type 2 diabetes (T2D), and to explore the relationships between muscle density and skeletal characteristics.
Methods: This cross-sectional study included 123 individuals with T2D, of whom 50 had diabetic neuropathy and 73 did not based on peripheral (MNSI, VPT, NCS, IENFD) and autonomic assessments (CARTs). Muscle morphology and density at the distal tibia, together with bone microarchitecture, were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT). Appendicular lean mass (ALM) and femoral-neck bone mineral density were measured by DXA. Muscle strength was evaluated using handgrip and knee-extension tests, while physical performance was assessed through the chair stand test, timed up-and-go (TUG), and usual gait speed. Regression analyses were adjusted for age, sex and BMI.
Results: Compared with participants without neuropathy, those with neuropathy had lower distal tibial muscle volume (β = −2367 mm³, 95% CI −3558 to −1176, p<0.001) and density (β = −8.11 HU, 95% CI −12.32 to −3.89, p<0.001) after adjustment for age, sex and BMI. Physical performance was also poorer (chair stand β = −2.0 stands, p<0.05; TUG +0.7 s, p<0.05; gait speed −0.13 m/s, p<0.01), while ALM and maximal strength did not differ. Higher muscle density was associated with more favourable bone characteristics, including greater femoral-neck bone mineral density (β = 0.004 g/cm² per HU, 95% CI 0.001 to 0.006, p<0.05), better cortical bone parameters (lower cortical porosity: β = −0.09 % per HU; total vBMD: β = 1.89 mg HA/cm³ per HU, 95% CI 0.84 to 2.94, p<0.05) and higher estimated tibial bone strength (failure load: β = 0.048 kN per HU, 95% CI 0.012 to 0.084, p<0.05).
Conclusions: Neuropathy in T2D seems to be associated with a broader neuromusculoskeletal phenotype, characterised by impaired muscle quality and physical performance despite apparently preserved muscle mass and maximal strength. The observed associations between muscle density and bone characteristics suggest a potential link between neuropathy, functional impairment and skeletal fragility.
Comments. A major strength of this study is its comprehensive phenotyping of nerve function, muscle morphology, physical performance and bone microarchitecture. Its findings highlight why conventional measures such as lean mass or maximal strength alone may fail to capture clinically relevant muscle impairment in people with diabetic neuropathy. Functional assessment may therefore provide complementary information when evaluating mobility and potential fall risk.
However, the cross-sectional design precludes causal inference, and the groups differed at baseline (older, more males, higher BMI, longer diabetes duration, more insulin use in the neuropathy group). Associations with muscle density were robust to additional adjustment, whereas those with physical performance were attenuated. Controls may include subclinical neuropathy, and HR-pQCT muscle density is an indirect marker of muscle quality.
Longitudinal studies are needed to determine whether these changes predict falls, fractures or functional decline, and whether targeted interventions can modify these outcomes.
Carla Greco
Reference. Graversen JL, Kvist AV, Sjogaard MB, Madsen MD, Rasmussen NH, Vestergaard P, Røikjer J. Impaired muscle quality and physical performance in diabetic neuropathy: associations with skeletal characteristics from the Deep Phenotyping Study. Diabetes Res Clin Pract. 2026 Oct 12;242:113609. doi: 10.1016/j.diabres.2026.113609. Epub ahead of print. PMID: 42863636.
