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Observational Study
. 2025 Jul;12(7):1408-1417.
doi: 10.1002/acn3.70072. Epub 2025 May 19.

The Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type

Long Davalos  1 , Brian C Callaghan  2 , Lavanya Muthukumar  2 , Simone Thomas  3 , Evan L Reynolds  2 , A Gordon Smith  4 , J Robinson Singleton  5 , Ahmet Höke  3 , Senda Ajroud-Driss  6 , Mazen M Dimachkie  1 , Stefanie Geisler  7 , David M Simpson  8 ; PNRR Study Group; Amro M Stino  2
Affiliations
Observational Study

The Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type

Long Davalos et al. Ann Clin Transl Neurol. 2025 Jul.

Abstract

Objective: Determine the association between diabetes and metabolic syndrome (MetS) burden (number of MetS criteria fulfilled) and pain, neuropathy severity, and fiber type involvement in individuals with established polyneuropathy.

Methods: The Peripheral Neuropathy Research Registry was queried for individuals with type 1 and type 2 diabetes (DPN) and non-diabetic peripheral neuropathy (cryptogenic sensory polyneuropathy and prediabetes) using cross-sectional observational data. Associations between diabetes or MetS burden and pain presence (yes/no), neuropathy severity (Total Neuropathy Score reduced), and fiber type involvement (pinprick, vibration, and proprioception examination-small, large, mixed) using logistic, linear, and multinomial regression models were determined.

Results: A total of 1112 participants were included (265 DPN, 847 non-diabetic peripheral neuropathy [NDPN]). Compared to NDPN, DPN participants were more likely to have pain, higher neuropathy severity, and mixed fiber involvement. In adjusted models, diabetes was associated with pain (odds ratio [OR] 1.85, CI: 1.15-3.03) and severity (point estimate [PE] 0.84, CI: 0.27-1.42), but not fiber type involvement. As the MetS burden increased, pain, neuropathy severity, and mixed fiber type involvement increased (p < 0.05 for trend). In adjusted models, MetS burden was associated with pain (OR 1.23, CI: 1.06-1.41) but not severity or fiber type involvement.

Interpretation: Participants with DPN were more likely to have pain, greater neuropathy severity, and possibly more mixed fiber involvement than those with NDPN. Similarly, increasing MetS burden also led to more painful neuropathy and possibly more severe neuropathy with more mixed fiber involvement.

Keywords: cryptogenic sensory polyneuropathy; diabetic neuropathy; idiopathic neuropathy; metabolic syndrome; metabolic syndrome burden.

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Conflict of interest statement

B.C.C. consults for DynaMed, performs medical legal consultations, including consultations for the Vaccine Injury Compensation Program, and receives research and editorial support from the American Academy of Neurology. A.G.S. reported receiving consulting fees from Merz, Sangamo, Argenx, and Alexion and data monitoring board fees from Eidos and Lexicon. A.H. consults for Pfizer, GenEdit, Eikonizo, HDAX Therapeutics, and Sangamo and receives editorial support from the American Neurological Association and research funding from DOD, NINDS, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Merkin Family Foundation, and Foundation for Peripheral Neuropathy. S.A.‐D. served on the advisory board for Amylyx Pharmaceutical and Orphazyme, served as a speaker for Biogen, and received honoraria from MDA, AANEM, and Medscape. M.M.D. consults for Abata/Third Rock, Abcuro, Amicus, ArgenX, Astellas, Cabaletta Bio, Catalyst, CNSA, Covance/Labcorp, CSL‐Behring, Dianthus, Horizon, EMD Serono/Merck, Ig Society Inc., Ipsen, Janssen, Medlink, Nuvig, Octapharma, Priovant, Sanofi Genzyme, Shire Takeda, TACT/Treat NMD, UCB Biopharma, Valenza Bio, and Wolters Kluwer Health/UpToDate and has received research grants or contracts, or educational grants from Alexion/AstraZeneca, Alnylam Pharmaceuticals, Amicus, Argenx, Bristol‐Myers Squibb, Catalyst, CSL‐Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, The Myositis Association, and UCB Biopharma/RaPharma. A.M.S. has consulted for Argenx, CSL Behring, Takeda, Sanofi, Immunovant, Annexon, and has received research support from Bristol Myers Squibb and the GBS‐CIDP Foundation. L.D., L.M., S.T., E.L.R., J.R.S., S.G., and D.M.S. have no relevant conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Prevalence of pain with increasing metabolic syndrome (MetS) components. Includes only complete observations with pain prevalence and MetS score. Overall N = 815, individual sample size based on glycemic status, −Normoglycemia (N = 360), Prediabetes (N = 248), Diabetes (N = 207). p values based on the chi‐square test for differences in pain prevalence with increasing MetS components within each group.
FIGURE 2
FIGURE 2
Prevalence of metabolic syndrome (MetS) components with increasing neuropathy severity. Severity is characterized by total neuropathy severity score (reduced), Mild = 0–8, Moderate = 9–15, severe = 16–20. Includes only complete observations with TNSr and MetS scores. Overall N = 815, individual sample size based on glycemic status, normoglycemia (N = 360), prediabetes (N = 248), diabetes (N = 207). p values based on the chi‐square test for differences in the number of MetS components with increasing neuropathy severity within each group.
FIGURE 3
FIGURE 3
Prevalence of fiber type with increasing metabolic syndrome (MetS) components. Includes only complete observations with fiber type and MetS score. Overall sample size = 718, individual sample size based on glycemic status, normoglycemia (N = 307), prediabetes (N = 222), diabetes (N = 189). p values based on the chi‐square test for differences in fiber type prevalence with increasing MetS components within each group.
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