Symptom-driven co-existence of diabetic autonomic neuropathy, peripheral neuropathy, and painful neuropathy

Diabetic Autonomic Neuropathy (DAN) and Diabetic Peripheral Neuropathy (DPN) are distinct complications of diabetes, but their co-existence remains underexplored. This study aimed to investigate the symptom-driven co-existence of DAN, DPN, and painful DPN.

In November 2022, an electronic survey was distributed to everyone with diabetes in the North Denmark Region (n = 29,155). The survey included demographic data, and validated questionnaires: the Michigan Neuropathy Screening Instrument (MNSI), Composite Autonomic Symptom Score-31 (COMPASS-31), and Douleur Neuropathique 4 Interview (DN4i). DPN was defined as MNSI ≥ 4, painful DPN as bilateral foot pain with DN4i ≥ 3, and DAN as COMPASS-31 ≥ 16. DAN was further stratified into: symptoms of autonomic dysfunction (SAD)- (< 16), SAD + (16-31), and SAD +  + (≥ 32).

Of 9,913 respondents, 7,321 provided complete data. Mean age was 64.8 yearsand 86.3% had type 2 diabetes. DPN prevalence among those with DAN was 44.6% in type 1 and 39.6% in type 2 diabetes. DPN prevalence rose with DAN severity: 11.1% in SAD-, 26.4% in SAD + , and 58.6% in SAD +  + (p < 0.01). Painful DPN followed a similar trend, increasing from 8.0% in SAD- to 50.2% in SAD +  + (p < 0.01). Linear regression demonstrated a strong association between COMPASS-31 and MNSI scores (p < 0.001), indicating that higher autonomic symptom burden was associated with greater severity of peripheral neuropathy.

DAN, DPN, and painful DPN frequently co-exist. Increasing DAN symptom severity is associated with higher prevalence of both DPN and neuropathic pain and showed a strong linear association with the severity of peripheral DPN, suggesting shared pathophysiological mechanisms beyond isolated small fiber involvement.