When metabolism harms nerves: neuropathy and arterial stiffness in prediabetes
Aims: Individuals with prediabetes are at high risk of developing distal symmetrical polyneuropathy (DSPN). This study aimed to determine the prevalence of DSPN in individuals with prediabetes and examine its associations with insulin resistance and cardiovascular outcomes.
Methods: This study performed a cross-sectional analysis of baseline data from a prospective cohort study including 160 adults with prediabetes attending an outpatient lipid and obesity clinic. Neuropathy was evaluated using the neuropathy symptom score (NSS), the neuropathy disability score (NDS), and age-specific vibration perception thresholds (VPT). Neuropathy was diagnosed using the following criteria: NSS ≥5 + NDS ≥3, or NDS ≥6, or abnormal VPT + NSS ≥3 + NDS ≥3. Arterial stiffness was evaluated using carotid–femoral pulse wave velocity (PWV).
Results: DSPN was diagnosed in 27 participants (16.9%). Individuals with DSPN were older, and had higher BMI and waist circumference compared with those without neuropathy. In multivariable analyses, insulin resistance and waist circumference were independently associated with DSPN. Participants with DSPN also exhibited higher arterial stiffness, reflected by greater pulse wave velocity and a higher prevalence of abnormal PWV (≥10 m/s), although PWV was not independently associated with DSPN after adjustment.
Conclusions: DSPN was present in a considerable proportion of individuals with prediabetes and was independently associated with central obesity and insulin resistance. Individuals with DSPN also exhibited greater arterial stiffness, suggesting a possible association between neuropathy and cardiovascular risk.
Comments: This study adds to existing evidence that DSPN is already detectable in a considerable proportion of individuals with prediabetes. The independent associations with waist circumference and insulin resistance support the concept that metabolic dysfunction may contribute to early nerve injury before the onset of overt diabetes. A strength of the study is the structured clinical assessment of neuropathy using validated scores. The diagnostic definition required both neuropathic symptoms and signs in most cases, broadly aligning with the Toronto criteria for “probable” neuropathy and increasing clinical relevance compared with definitions relying solely on symptoms or signs. Consecutive recruitment from a specialized outpatient clinic further strengthens the study by reflecting real-world clinical populations, although this approach may introduce some selection bias and limit generalisability. The prospective design of the cohort is also noteworthy, as it may enable future longitudinal analyses examining neuropathy progression and cardiometabolic risk. Several limitations should be considered. The assessment focused primarily on large fibre dysfunction and did not include dedicated measures of small fibre neuropathy, such as quantitative sensory testing, skin biopsy, or corneal confocal microscopy. As small fibre injury may represent the earliest manifestation of neuropathy in dysglycaemia, its absence may underestimate early neuropathic changes in this population. Overall, the findings support the presence of neuropathy in prediabetes, and future follow-up of this prospective cohort may provide important insights into the early stages of neuropathy, especially if measures of small fibre dysfunction are included.
Mette Krabsmark Borbjerg
Reference. Anastasiou G, Papanas N, Barkas F, Tentolouris N, Liamis G, Michalis LK, Bechlioulis A, Kalaitzidis R, Liberopoulos E. Distal symmetrical polyneuropathy in prediabetes is associated with abdominal obesity and insulin resistance. Diabetes Res Clin Pract. 2026 Mar;233:113140. doi: 10.1016/j.diabres.2026.113140. Epub 2026 Feb 4. PMID: 41651186.
