Skeletal muscle microvascular dysfunction in diabetic peripheral neuropathy
Aims: This study investigated whether diabetic peripheral neuropathy (DPN) is associated with impaired skeletal muscle microvascular function in individuals with type 1 diabetes (T1D), and whether microvascular function differs according to the presence of neuropathic pain and small fiber neuropathy.
Methods: In this cross-sectional study, four groups were examined: Individuals with T1D and DPN with and without pain, individuals without DPN, and age-matched healthy controls. Participants underwent blood oxygen level-dependent (BOLD) MRI. Microvascular reperfusion following thigh cuff occlusion was assessed in lower leg skeletal muscles. Peak BOLD response and -me-to-peak (TTP) were used as measures of reactive hyperaemia.
Results: Peak BOLD responses were lower in individuals with painful DPN (105% of baseline) than in those with T1D without DPN (108%, p=0.025) and healthy controls (108%, p=0.005). Painless DPN was also associated with a lower peak response than healthy controls (106%, p=0.032). TTP did not differ between the main groups. When participants were regrouped according to small fiber burden, participants with confirmed small fiber neuropathy demonstrated both a reduced peak BOLD response (105 %, p<0.001) and delayed TTP (42.1 vs. 31.5s, p=0.003) compared with healthy controls.
Conclusions: Skeletal muscle microvascular function appears impaired in individuals with T1D and DPN, irrespective of neuropathic pain, with greater impairment observed on those with confirmed small fiber neuropathy.
Comments. This Muscle dysfunction in diabetes is multifactorial. While the contribution of DPN to muscle weakness and atrophy through denervation and incomplete reinnervation is well established, its impact on skeletal muscle microvascular function and the derived ability to meet increased metabolic demands during exercise is less well understood. Importantly, microvascular dysfunction may occur despite preserved macrovascular function and therefore remain undetected by conventional assessment of large-vessel disease. This study provides intriguing evidence of impaired skeletal muscle microvascular function in individuals with T1D and DPN, and the finding of greater microvascular impairment with greater small fiber burden is interesting. However, as this analysis was not adjusted for large fiber neuropathy, the findings are best interpreted as indicating that greater overall neuropathy burden is associated with greater microvascular dysfunction. Besides the cross-sectional design and small sample size, important limitations include the inability of BOLD MRI to determine the underlying cause of the microvascular dysfunction, and the lack of assessment of potentially important factors such as physical activity, muscle strength, and mass. Still, these findings raise the possibility that microvascular dysfunction represents an additional pathway linking DPN to impaired muscle function. This may help explain why improvements in functional capacity following exercise interventions are not always parallelled by changes to quantitative muscle properties (Khan KS et al Diabetologia. 2022;65:620-631). Future studies should determine whether microvascular dysfunction directly contributes to impaired muscle function and whether exercise intervention can improve microvascular health in these individuals.
Anders Stouge
Reference. Larsen RG, Croosu SS, Røikjer J, Hansen RK, Mark EB, Hansen TM, Mørch CD, Ejskjær N, Frøkjær JB. Impact of diabetic peripheral neuropathy on skeletal muscle microvascular function: A blood oxygen level dependent magnetic resonance imaging study. J Diabetes ComplicaHons. 2026 Sep 14;40(11):109414. doi: 10.1016/j.jdiacomp.2026.109414. Epub ahead of print. PMID: 42743612.
