Dear editor,
Davalos et al. [1] examined 1112 registry participants with distal symmetrical polyneuropathy and concluded that diabetes and a higher metabolic syndrome (MetS) burden independently increase pain prevalence and neuropathy severity. The dataset is valuable, but several methodological limitations temper causal interpretation.
Selection and Missing‐Data Bias: Recruitment from seven US tertiary centers and complete‐case analyses (27% missing lipid results; 13% missing fiber‐type data) risk excluding healthier individuals and potentially inflating associations. Registry volunteers may differ systematically from community populations, limiting external validity.
Cross‐Sectional Design and Reverse Causality: Because exposure (MetS burden) and outcome were measured simultaneously, temporality cannot be established; lifestyle change or analgesic use after neuropathic pain onset could explain the observed odds ratios [2].
Exposure Misclassification: Central obesity—the strongest metabolic driver of neuropathy—is absent; BMI ≥ 27 kg/m2 is an imprecise surrogate for visceral adiposity [3]. Hypertension and glycemic status were defined based on single measurements, which increased random error.
Outcome Misclassification: Pain was any Numeric Rating Scale value > 0, conflating occasional discomfort with clinically significant neuropathic pain. Fiber‐type classification relied solely on bedside examination; objective modalities, such as intra‐epidermal nerve‐fiber density or nerve‐conduction studies, were unavailable in up to 27% of cases, inviting differential misclassification [4].
Residual Confounding: Adjusted models omitted diabetes duration, HbA1c, waist circumference, alcohol intake, and pain‐modifying medications. These factors could explain the modest effect size observed for MetS burden (OR 1.23 for pain).
In summary, prospective studies should obtain repeated metabolic measures, include objective small‐ and large‐fiber diagnostics for all participants, adjust for diabetes duration and treatment, and use multiple imputation to handle missing data.
Author Contributions
Majid Khalilizad: investigation, writing – original draft preparation, supervision. Ebrahim Hejazian: investigation, writing – original draft preparation. Mohammad Barary: investigation, writing – original draft preparation, writing – review and editing. Mostafa Javanian: investigation, writing – original draft preparation. Soheil Ebrahimpour: investigation, writing – original draft preparation, supervision.
Conflicts of Interest
The authors declare no conflicts of interest.
Linked Articles
Commentary on “The Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type”, https://doi.org/10.1002/acn3.70072.
Acknowledgments
The authors thank the Infectious Diseases and Tropical Medicine Research Center of Babol University of Medical Sciences.
Funding: The authors received no specific funding for this work.
Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.