Neuropathic pain with and without diabetic peripheral neuropathy in type 1 diabetes

Aims: In this study, the incidence, prevalence, remission and risk factors of neuropathic pain in type 1 diabetes (T1D) were evaluated in the Epidemiology of Diabetes Interventions and Complications (EDIC) cohort.

Methods: This was a longitudinal study evaluating self-reported neuropathic pain (NP) in participants enrolled in EDIC. EDIC is the observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. In this study, NP (defined as a “yes” to questions 2 and/or 6 of the Michigan Neuropathy Screening Instrument (MNSI) was evaluated in participants of the EDIC cohort with and without clinical signs of diabetic peripheral neuropathy (DPN; DPN+ = an MNSI exam score >2; DPN- = MNSI </=2) at years 1 and 26 of EDIC follow-up. NP remission was also assessed in a subset of participants using annual reclassification rates.

Results: Among 1324 participants, the cumulative incidence of NP at 26 years was 57%. The incidence of the first occurrence of NP in the DPN+ group was 36% and in those in the DPN- group was 46%. Participants in the conventional therapy arm of the original DCCT study had a higher risk of NP DPN+. The prevalence of NP increased from 9% to 20% at year 26. Nearly 15% of participants experienced remission of NP within 1 year with average remission rates of 8.7% in DPN+ participants and 6.2% in DPN- participants. NP remission rates were similar in DPN+ and DPN- participants regardless of NP pharmacotherapy use. Risk factors for NP included higher hemoglobin A1c (A1c) and cigarette smoking in both DPN+ and DPN- participants. Additional risk factors for NP in DPN- participants included female sex and a higher pulse rate.

Conclusions: The incidence of NP in T1D is high even when clinical signs of DPN are not present. Risk factors for NP consistently include higher A1c and cigarette smoking and female sex is associated with NP specifically in those without clinical signs of DPN. The incidence of NP was higher than the prevalence at 26 years, suggesting frequent remission. The use of medications for NP does not fully explain NP remission rates.

Comments. The incidence and prevalence of NP in T1D was evaluated in this longitudinal observation studies. Notable strengths include the large cohort size and robust longitudinal data in this well-characterized cohort. Limitations include the measures of NP as validated assessments for neuropathic pain were not used. Additionally, the evaluation of DPN did not include a specific small-fiber instrument. This study suggests that the NP can be problematic even in the absence of clinical signs of DPN, particularly in females with T1D.

Kara Mizokami-Stout

Reference. Braffett BH, El Ghormli L, Albers JW, Feldman EL, Herman WH, Gubitosi-Klug RA, Martin CL, Orchard TJ, White NH, Lachin JM, Perkins BA, Pop-Busui R; DCCT/EDIC Research Group. Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes. Diabetes Care. 2024 Sep 1;47(9):1559-1567. doi: 10.2337/dc23-1749. PMID: 38300889; PMCID: PMC11362121.

https://diabetesjournals.org/care/article/47/9/1559/154181/Neuropathic-Pain-With-and-Without-Diabetic