Blood IL-6 Levels Rise in Diabetic Neuropathy, but Gene Variants Fall Short

Diabetic neuropathy, one of the most common complications of long-standing diabetes, has been repeatedly linked to chronic low-grade inflammation, and two immune signaling molecules—interleukin-6 (IL-6) and interleukin-10 (IL-10)—sit at the center of that process. A new case-control study from Bangladesh examined whether both the blood levels of these cytokines and common genetic variants in their genes are associated with the condition. The researchers enrolled 225 participants in three equal groups of 75: diabetic patients with neuropathy, diabetic patients without neuropathy, and healthy controls. Genomic DNA was extracted from each participant to genotype two single-nucleotide polymorphisms, IL-6 rs1800796 and IL-10 rs1800896, using polymerase chain reaction, while serum cytokine concentrations were quantified with enzyme-linked immunosorbent assays.

The clearest signal came from circulating protein rather than DNA. Serum IL-6 levels were significantly higher in the neuropathy group than in either diabetic patients without neuropathy or healthy controls (p < 0.0001), and the highest concentrations were observed among individuals carrying the IL-6 rs1800796 CC genotype. In unadjusted analyses, the IL-6 CC genotype was associated with increased odds of diabetic neuropathy compared with healthy controls (OR = 4.813, 95% CI: 1.752–13.85, p = 0.0040), and the IL-10 GG genotype also showed a nominal association (OR = 2.679, 95% CI: 1.000–6.751, p = 0.0373). These genetic effects, however, did not survive scrutiny: neither the IL-6 nor the IL-10 genotype remained independently associated with neuropathy after multivariable adjustment, meaning the apparent genetic risk likely reflected confounding by other participant characteristics rather than a direct causal effect of the variants.

The anti-inflammatory counterpart told a different story. Serum IL-10 levels did not differ significantly among the three study groups (p = 0.0948), and statistical analysis showed that IL-10 demonstrated limited discriminatory performance in separating patients with neuropathy from the other participants. Combined genotype analyses, in which the two polymorphisms were considered together, produced several nominal associations, but the authors characterized these findings as exploratory and did not claim robust independent genetic effects. In contrast, serum IL-6 showed promising discriminatory ability in distinguishing patients with diabetic neuropathy from both diabetic patients without the complication and healthy controls, positioning the cytokine as the standout measurement in the dataset.

The authors conclude that these findings support further investigation of serum IL-6 as a potential candidate biomarker for diabetic neuropathy, whereas the independent contribution of the investigated IL-6 and IL-10 polymorphisms remains uncertain. They are careful to note that larger prospective studies with independent external validation are required before any clinical application can be considered. For now, the study adds population-specific evidence from a Bangladeshi cohort that elevated circulating IL-6 tracks with nerve damage in diabetes, while suggesting that the two gene variants alone are not reliable predictors of the condition.

Subject of Research: Association of IL-6 and IL-10 serum levels and gene polymorphisms with diabetic neuropathy in a Bangladeshi case-control cohort

Article Title: Association of IL-6 and IL-10 serum levels with genetic variants in diabetic neuropathy: Clinical findings from a Bangladeshi patient cohort

Article References: Das, R., Raihan, S. Z., Paul, S., Patwary, M. S. A., & Chowdhury, A. K. A. (2026). Association of IL-6 and IL-10 serum levels with genetic variants in diabetic neuropathy: Clinical findings from a Bangladeshi patient cohort. PLOS One, 21(10), e0360933. https://doi.org/10.1371/journal.pone.0360933

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DOI: 10.1371/journal.pone.0360933

Keywords: diabetic neuropathy, interleukin-6, interleukin-10, cytokines, gene polymorphisms, case-control study, biomarkers, Bangladesh, inflammation, ELISA, Association, IL-6