Background & Aims

Diabetic polyneuropathy (DPN) is a common complication to type 2 diabetes (T2D). Knowledge is lacking about the natural course of DPN. Neuropathic pain (NP) is common in DPN but there is almost no longitudinal studies on risk factors for NP in DPN. We examined the development of DPN over time to describe the natural history of sensory changes that occur during the course of the disease as well as the development of NP in DPN.

Methods

Originally, 389 patients with newly diagnosed T2D and 97 controls without diabetes were recruited to establish the diagnosis of DPN. The Toronto consensus criteria were used to classify patients into possible, probable and confirmed DPN. For this study all participants from the baseline study were invited for a 5-year follow-up examination and underwent detailed phenotyping combining both bedside sensory examination, questionnaires, quantitative sensory testing (QST), nerve conduction studies (NCS) and skin biopsies. Patients with painless DPN at baseline were evaluated for NP at follow-up.

Results

184 patients with T2D (47.3 %) completed follow-up. Mean diabetes duration at baseline: 5.9 years. From baseline to follow-up the percentage of patients with confirmed DPN had increased (35.8 % to 50.3 %) and the percentage of patients with probable DPN had decreased (27.2 % to 14.6 %). The percentage of patients with possible and no DPN were similar. Patients with DPN had increased spread of hyposensitivity at bedside examination, more hyposensitivity on QST and lower NCS Z-scores at follow-up. 55 patients (29.9 %) had painless DPN at baseline. 21 (38.2 %) developed NP and 34 (61.8 %) did not. More NP-patients at follow up were female compared to patients without NP (47.6 % vs 17.6 %, p=0.031). NP-patients had worse baseline warmth detection thresholds (mean Z-value -1.3 vs -0.8, p=0.012) and thermal sensory limen (mean Z-value -1.5 vs -1.0, p=0.04) and lower sural SNAP amplitudes (mean left Z-value -1.4 vs -0.3, p=0.015, mean right Z-value -1.4 vs -0.3, p=0.039) than non-NP patients.

Conclusions

– In T2D, having at least probable DPN five years after diabetes diagnosis is associated with progression of DPN sensory signs ten years after diabetes diagnosis.
– Patients with possible or no DPN had a lower risk of progression.
– Almost 40 % of patients with painless DPN at baseline developed NP at follow-up.
– Patients who developed NP ten years after diabetes diagnosis were more affected on both small fiber and large fiber measurements than patients who did not.

Results are preliminary and not yet peer-reviewed.

References

Callaghan BC, Price RS, Chen KS, Feldman EL. The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review. JAMA Neurol 2015;72(12):1510-8. DOI: 10.1001/jamaneurol.2015.2347.
Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers 2019;5(1):41. DOI: 10.1038/s41572-019-0092-1.
Jensen TS, Karlsson P, Gylfadottir SS, et al. Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management. Brain 2021;144(6):1632-1645. DOI: 10.1093/brain/awab079.
Gylfadottir SS, Itani M, Kroigard T, et al. Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes. Eur J Neurol 2020;27(12):2575-2585. DOI: 10.1111/ene.14469.
Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010;33(10):2285-93. DOI: 10.2337/dc10-1303.

Presenting Author

Peter Kolind Brask-Thomsen

Poster Authors

Peter Kolind Brask-Thomsen, MD

MD, PhD-student

Danish Pain Research Center, Department of Clinical Medicine, Aarhus University

Lead Author

Páll Karlsson

MSc

Danish Pain Research Center, Department of Clinical Medicine, Aarhus University

Lead Author

Troels Staehelin Jensen

MD

Danish Pain Research Center

Lead Author

Nanna Finnerup

The Danish Pain Research Center - Department of Clinical Medicine, Aarhus University

Lead Author

Sif Gylfadottir

ORG-100009397

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral