Examining Painful vs Nonpainful Diabetic Polyneuropathy Over a 5-Year Period

Among patients with type 2 diabetes (T2D) and diabetic polyneuropathy (DPN), some patients with nonpainful DPN may develop neuropathic pain over a 5-year period while others with painful DPN may experience neuropathic pain relief during the same period, according to study results published in Pain.

Up to 35% of patients with DPN are estimated to have painful DPN, which has been associated with poor sleep, low quality of life, and anxiety and depression. Medical treatment of painful DPN has been found to relieve symptoms in less than half of patients, and only a few longitudinal studies of neuropathic pain have been conducted in patients with polyneuropathy. No such studies are known to have been conducted in patients with T2D and polyneuropathy. 

Between 2021 and 2023, researchers in Denmark conducted a prospective 5-year follow-up of a subgroup of 184 patients with T2D whose data were obtained from a nationwide Danish registry. All patients had undergone detailed clinical phenotyping for DPN based on the Toronto consensus criteria as part of a prior questionnaire study of neuropathy symptoms conducted between 2016 and 2018 that included 389 patients. The researchers’ goal was to assess progression of painful DPN over time. They used multivariate logistic regression models to identify factors linked to development or regression of patients’ neuropathic pain.

The follow up rate was 47.3% (with follow-up for 184 of 389 patients) and the mean (SD) follow-up duration was 5 (0.6) years. In comparing patients who completed follow-up vs those who did not, no significant between-group differences were found in terms of patients’ age, sex, diabetes duration, BMI, Toronto Clinical Neuropathy Score, Michigan Neuropathy Screening Instrument questionnaire results, the percentage of patients with at least probable DPN or painful DPN, and patients’ average pain scores.

Across the total patient population, the estimated prevalence of at least probable painful DPN increased from 11.5% at baseline to 14.8% at follow-up, with a median diabetes duration of 11 years.

Among 64 patients with nonpainful DPN at baseline, 38.2% had developed pain by follow-up. In comparison, 28.9% of the 38 patients without dysesthesia at baseline developed pain over the same period.

Women were more likely than men to develop pain (odds ratio, 4.8; 95% CI, 0.9-25.6; P =0.07). Other patients more likely to experience pain were those with lower sensitivity to warm stimuli on quantitative sensory texting (QST) at baseline and follow-up and lower sural sensory nerve action potential amplitudes at baseline and follow-up.

In comparison, relief from pain was associated with lower baseline BMI and cholesterol levels, as well as higher baseline sensitivity to cold, mechanical, and vibratory stimuli as measured by QST.

Notably, a higher percentage of patients with dysesthesia developed pain than patients who did not have pain or dysesthesia, supporting the researchers’ hypothesis that dysesthetic DPN is a precursor to neuropathic pain. Commenting on their methodology, they noted, “This study classified any patient report of positive, nonpainful symptoms as paresthesia and did not take unpleasantness into account and thus likely grouped dysesthesia under paresthesia.” Additional research, they emphasized, is needed to establish the relationship between dysesthesia and the risk of developing neuropathic pain.

Limitations of this study include its relatively small sample size and low follow-up rate, which impact generalizability of the findings.

The researchers concluded, “[I]n this first cohort study on neuropathic pain in patients with T2D and DPN, 32.8% of patients with nonpainful DPN developed neuropathic pain over a 5-year period, but interestingly 28.9% of patients with [painful] DPN experienced relief from neuropathic pain over the same period.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Clinical Pain Advisor