The Association of Inflammatory Factors With Peripheral Neuropathy: The Study of Women's Health Across the Nation

J Clin Endocrinol Metab. 2023 Mar 10;108(4):962-970. doi: 10.1210/clinem/dgac612.


Purpose: Previous work has focused on the role of diabetes in peripheral neuropathy (PN), but PN often occurs before, and independently from, diabetes. This study measures the association of cardiometabolic and inflammatory factor with PN, independent of diabetes.

Methods: Study of Women's Health Across the Nation participants (n = 1910), ages 60 to 73 (mean 65.6) were assessed for PN by symptom questionnaire and monofilament testing at the 15th follow-up visit (V15). Anthropometric measures and biomarkers were measured at study baseline approximately 20 years prior, and C-reactive protein (CRP) and fibrinogen were measured longitudinally. Log-binomial regression was used to model the association between metabolic syndrome (MetS), obesity (≥35 body mass index), CRP, and fibrinogen with PN, adjusting for sociodemographic and health behavior measures.

Results: Baseline MetS [prevalence ratio (PR) 1.79, 95% CI (1.45, 2.20)], obesity [PR 2.08 (1.65, 2.61)], median CRP [PR 1.32 per log(mg/dL), (1.20, 1.45)], and mean fibrinogen (PR 1.28 per 100 mg/dL, (1.09, 1.50)] were associated with PN symptoms at V15. After excluding participants with baseline diabetes or obesity, MetS [PR 1.59 (1.17, 2.14)] and CRP [PR 1.19 per log(mg/dL), (1.06, 1.35)] remained statistically significantly associated with PN. There was a negative interaction between MetS and obesity, and the association between these conditions and PN was mediated by CRP.

Conclusions: Cardiometabolic factors and inflammation are significantly associated with PN, independent of diabetes and obesity. CRP mediates the relationship of both obesity and MetS with PN, suggesting an etiological role of inflammation in PN in this sample.

Keywords: CRP; fibrinogen; inflammation; metabolic syndrome; peripheral neuropathy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases* / complications
  • Diabetes Mellitus*
  • Female
  • Fibrinogen / analysis
  • Humans
  • Inflammation / complications
  • Metabolic Syndrome* / complications
  • Metabolic Syndrome* / etiology
  • Middle Aged
  • Obesity / complications
  • Obesity / epidemiology
  • Peripheral Nervous System Diseases* / epidemiology
  • Peripheral Nervous System Diseases* / etiology
  • Risk Factors
  • Women's Health


  • C-Reactive Protein
  • Biomarkers
  • Fibrinogen