Early Diagnosis through Estimation of Inflammatory Biomarkers and the Neuroprotective Role of Metformin in Diabetic Peripheral Neuropathy

Abstract

Purpose: Diabetic peripheral neuropathy (DPN), a chronic neurological complication of type 2 diabetes mellitus (T2DM) with signs and symptoms of peripheral nerve dysfunction such as numbness, tingling or burning sensation, paresthesias etc. Several lacunae exist in relation to the cause and effect of DPN. Therefore diagnosis, as well as treatment of DPN remains unsatisfactory. The involvement of chronic low-grade inflammation in DPN is a rapidly emerging concept and therefore the present study adds weight to it. We estimated some of the biomarkers of inflammation which may be the early markers of DPN. This study is the earliest of its kind to correlate the biomarker levels with metformin, a drug less reported in terms of its anti-inflammatory and neuroprotective activity. 
 Methods: After approval from the institutional human ethical committee, 90 patients attending the outpatient ward of a tertiary care hospital were included in the study. They were divided into two groups: M- group (patients on non metformin) and M+ group (patients on metformin). 5ml serum sample from each patient was processed for estimation of IL-1, IL-6, IL-8, TNF- α, INF- α, GMCSF and MCP-1 according to the manufacturer’s instructions on the commercially available ELISA kit. Metformin levels in the serum were estimated by HPLC. Data was put into statistical analysis. 
 Results: Results showed that IL-1, IL-2, IL-6 and TNF- α were significantly higher in the M- group. The difference was statistically significant between the two groups. The level of biomarkers showed a negative correlation with drug levels in the initial 2m treatment with the drug but was not statistically significant. However, after 6m treatment with metformin the correlation was found to be of statistical significance.
 Conclusion: we conclude that these biomarkers can be work tested for their clinical utility to be used as diagnostic tools for early detection of DPN and short-term metformin treatment greatly benefits DPN patients. Longitudinal studies may be more insightful as to the long term neuroprotective action of metformin.