Ryan Godsk Larsen, Suganthiya Santhiapillai Croosu, Johan Røikjer, Rasmus Kopp Hansen, Esben Bolvig Mark, Tine Maria Hansen, Carsten Dahl Mørch, Niels Ejskjær, Jens Brøndum Frøkjær
These findings suggest that skeletal muscle microvascular function is compromised in individuals with T1DM, particularly those with DPN, neuropathic pain, and small fiber neuropathy. This reduced perfusion capacity may contribute to functional impairments in lower limb musculature, highlighting the need for further investigation into underlying mechanisms and potential therapeutic strategies.
BACKGROUND AND AIMS: Diabetic peripheral neuropathy (DPN) is associated with impaired skeletal muscle function, particularly in the lower limbs. However, microvascular function in lower leg skeletal muscles among individuals with type 1 diabetes mellitus (T1DM), stratified by DPN and neuropathic pain status, remains poorly understood. This study examined blood oxygen level-dependent (BOLD) responses to ischemia-reperfusion in the tibialis anterior (TA), soleus (SO), and medial gastrocnemius (GM) muscles.
METHODS: Participants included individuals with T1DM and painful DPN (T1DM + PDPN; n = 19), T1DM with painless DPN (T1DM + DPN; n = 18), T1DM without DPN (T1DM-DPN; n = 15), and age-matched healthy controls (n = 20). While supine in a Magnetic Resonance scanner, participants underwent 5 min of thigh cuff occlusion followed by reperfusion, during which BOLD imaging captured peak and time-to-peak (TTP) in TA, SO, and GM.
RESULTS: Across muscles, peak BOLD was lower in T1DM + PDPN (105.0% of baseline) compared to both T1DM-DPN (107.9%; p = 0.025) and controls (108.4%; p < 0.01), and lower in T1DM + DPN (105.8%) compared to controls (p < 0.01). No significant group differences were found in TTP. Additional analyses revealed that individuals with confirmed small fiber neuropathy exhibited both a diminished (105.3%) and delayed (42.1 s) BOLD response across muscles compared to controls (31.5 s; p < 0.01).
CONCLUSION: These findings suggest that skeletal muscle microvascular function is compromised in individuals with T1DM, particularly those with DPN, neuropathic pain, and small fiber neuropathy. This reduced perfusion capacity may contribute to functional impairments in lower limb musculature, highlighting the need for further investigation into underlying mechanisms and potential therapeutic strategies.