Glycemic control modifies the association between systemic inflammatory indices and diabetic neuropathy: Evidence from NHANES

Abstract

Background and Objective: Chronic low-grade inflammation is increasingly recognised as a key contributor to diabetic peripheral neuropathy (DPN). However, there is limited evidence on inflammatory markers. We therefore examined the association between hematologic inflammatory indices, namely, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII), with lower limb neuropathy. Methodology: We conducted a cross-sectional analysis of adults with diabetes aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Lower limb neuropathy was defined using standardized 10-g monofilament testing. Inflammatory indices (NLR, PLR, MLR, and SII) were calculated from complete blood counts and analyzed as continuous variables and tertiles. Survey-weighted logistic regression models were used to evaluate associations after adjustment for demographic factors, glycemic control, cardiovascular comorbidities, and lifestyle variables. Subgroup analyses were performed among individuals with poor glycemic control (HbA1c >8%).  Results: In the overall cohort, inflammatory indices were not independently associated with lower limb neuropathy in fully adjusted models. However, in individuals with HbA1c >8%, higher NLR and SII were significantly associated with increased odds of neuropathy, with graded relationships observed in tertile-based analyses.  Conclusions: Although systemic inflammatory indices were not significantly associated with neuropathy in the overall diabetic population, elevated NLR and SII were associated with neuropathy among individuals with poor glycemic control. Given the cross-sectional nature of data and limited adjustment of confounders, results must be interpreted with caution.