Diabetic Peripheral Neuropathy: The Role of Inflammation and Biomarkers


Diabetic Peripheral Neuropathy: The Role of Inflammation and Biomarkers


Diabetic peripheral neuropathy (DPN) is a chronic neurological complication of type 2 diabetes mellitus (T2DM) that is characterized by signs and symptoms of peripheral nerve dysfunction, such as numbness, tingling, burning sensation, and paresthesias. Despite its prevalence and impact on patient quality of life, there are still many unanswered questions about the cause and effect of DPN, leading to unsatisfactory diagnosis and treatment outcomes.

The Role of Inflammation in DPN

Emerging research suggests that chronic low-grade inflammation plays a significant role in the development and progression of DPN. Inflammation is believed to contribute to nerve damage and dysfunction by promoting oxidative stress, impairing neurotrophic support, and disrupting signaling pathways involved in nerve regeneration and repair. Understanding the role of inflammation in DPN could lead to new diagnostic and therapeutic approaches for this condition.

Biomarkers of Inflammation and Their Clinical Utility

Several biomarkers of inflammation have been identified as potential indicators of DPN. These biomarkers, including interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), interferon-alpha (INF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP-1), have been found to be elevated in patients with DPN. Measuring these biomarkers could potentially be used as diagnostic tools for the early detection of DPN.

Metformin: An Anti-inflammatory and Neuroprotective Drug

Metformin is a commonly prescribed drug for the management of T2DM. It is known for its ability to lower blood glucose levels, but recent studies have also suggested that metformin has anti-inflammatory and neuroprotective properties. By inhibiting the production of pro-inflammatory cytokines and promoting the activation of AMP-activated protein kinase (AMPK), metformin may help reduce inflammation and protect against nerve damage in DPN.

Study Design and Findings

In a study involving 90 patients with T2DM, researchers investigated the association between biomarker levels and metformin treatment. The patients were divided into two groups: one group received metformin (M+ group), and the other group did not receive metformin (M- group). Serum samples were collected from each patient and analyzed for levels of IL-1, IL-6, IL-8, TNF-α, INF-α, GM-CSF, and MCP-1 using commercially available ELISA kits. Metformin levels in the serum were also measured using high-performance liquid chromatography (HPLC).

The results showed that IL-1, IL-2, IL-6, and TNF-α levels were significantly higher in the M- group compared to the M+ group. There was a negative correlation between the levels of these biomarkers and metformin levels in the initial 2 months of treatment, although it was not statistically significant. However, after 6 months of treatment with metformin, the correlation became statistically significant. This suggests that metformin may have a beneficial effect on reducing inflammation in DPN.


In conclusion, this study provides evidence that biomarkers of inflammation, such as IL-1, IL-6, IL-8, and TNF-α, may be useful diagnostic tools for the early detection of DPN. Additionally, the study highlights the potential anti-inflammatory and neuroprotective effects of metformin in the management of DPN. Further longitudinal studies are needed to better understand the long-term neuroprotective action of metformin in DPN.


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Table 1. Biomarkers of Inflammation and Their Potential Diagnostic Utility in DPN

BiomarkerFunctionDiagnostic Utility
IL-1Induces inflammation and plays a role in nerve damagePotential diagnostic tool for early detection of DPN
IL-6Promotes inflammation and is involved in neural signalingPotential diagnostic tool for early detection of DPN
IL-8Induces inflammation and angiogenesisPotential diagnostic tool for early detection of DPN
TNF-αPromotes inflammation and is involved in nerve damagePotential diagnostic tool for early detection of DPN
INF-αPlays a role in immune response and inflammationPotential diagnostic tool for early detection of DPN
GM-CSFStimulates the growth and activation of immune cellsPotential diagnostic tool for early detection of DPN
MCP-1Promotes inflammation and recruits immune cells to the site of injuryPotential diagnostic tool for early detection of DPN

Note: IL: Interleukin, TNF-α: Tumor Necrosis Factor-alpha, INF-α: Interferon-alpha, GM-CSF: Granulocyte-Macrophage Colony-Stimulating Factor, MCP-1: Monocyte Chemoattractant Protein-1.


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