Sensory phenotypes provide insight into the natural course of diabetic polyneuropathy.

We aimed to investigate the characteristics and longitudinal course of sensory phenotypes identified through Quantitative Sensory Testing in the frame of diabetic polyneuropathy (DSPN). 316 individuals with diabetes mellitus (DM) were examined (78.8% T2DM), of which 250 were follow-up visits 1, 2 and/or 4 (2.88±1.27) years. Allocation into four sensory phenotypes (healthy, thermal hyperalgesia-TH, mechanical hyperalgesia-MH, and sensory loss-SL) at every timepoint was based on QST profiles of the right foot. Cross-sectional analyses demonstrated a gradual worsening of clinical and electrophysiological sensory findings, and increased DSPN prevalence across the groups culminating in SL. Motor nerve impairment was observed solely in SL. Longitudinal analysis revealed a distinct pattern of the phenotype's developmental course (healthy to TH, to MH, to SL). Baseline MH exhibited the highest risk of transition to SL. Regression to healthy was uncommon and mostly observed in TH. Among those without DSPN initially, presence or future occurrence of SL was associated with a three- to fivefold higher likelihood of DSPN development. Our comprehensive longitudinal study of phenotyped patients with DM elucidates the natural course of DSPN. QST-based sensory examination together with other tools for phenotyping may perhaps be useful to determine the natural course of diabetic neuropathy, to identify patients at high risk for DSPN and guide preventive and therapeutic interventions.