Neuropathic pain in diabetic polyneuropathy: a 5-year prospective study.

There are few prospective studies on neuropathic pain in diabetic polyneuropathy (P-DPN). We aimed to examine the development of P-DPN over time as well as factors associated with both the development of and relief from pain. In this 5-year follow-up study, we included 102 patients with at least probable DPN at baseline, according to the Toronto consensus criteria, recruited from a nationwide Danish cohort of 5514 patients with newly diagnosed type 2 diabetes between 2016 and 2018. All participants underwent detailed phenotyping of both DPN and pain, consisting of a bedside sensory examination, quantitative sensory testing (QST), skin biopsies, and nerve conduction studies at baseline and follow-up. The estimated prevalence (95% CI) of at least probable P-DPN increased from 11.5% (8.2; 14.9) at baseline to 14.8% (9.2; 20.4) at follow-up, with a median (interquartile range) diabetes duration of 11.0 (9.2, 12.2) years. Among 64 patients with baseline nonpainful DPN, 38.2% developed pain at follow-up, while 28.9% of 38 patients with baseline P-DPN did not have pain at follow-up. A higher proportion of patients with baseline dysesthesia developed pain (42.9%), compared with patients without dysesthesia (27.9%, Χ2-test for trend: P < 0.0001). Development of pain was associated with female sex, lower baseline sensitivity to warm stimuli on QST, and lower baseline sural sensory nerve action potential amplitudes. Relief from pain was associated with lower baseline body mass index and cholesterol, as well as higher sensitivity to cold, mechanical, and vibratory stimuli on QST at baseline. This detailed study identified risk factors for neuropathic pain development and cessation.