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Got Tingly Feet? 6 Biomarkers for Polyneuropathy Risk Identified

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Polyneuropathy is damage or disease affecting peripheral nerves, and the first symptoms are often tingly sensations in the feet.  Although polyneuropathy is present in about 30% of people with diabetes, it is often undiagnosed. However, findings from a recent study published in Diabetes might help to change that.

Polyneuropathy is one of the most common complications in people with diabetes, and can also occur with certain risk factors or diseases before the onset of diabetes.

Scientists from the German Diabetes Center (DDZ) in Dusseldorf, in cooperation with colleagues from the Helmholtz Center Munich (HMGU), both partners in the German Center for Diabetes Research (DZD), have now shown for the first time that six biomarkers of inflammation increase the risk of polyneuropathy.

Although many patients suffer from polyneuropathy, relatively little is known about its development, which also limits therapeutic options. So far it has been known that inflammatory processes contribute to other diabetic complications such as heart attack or stroke.

Therefore, the group carried out extensive analysis of biomarkers that characterize inflammatory processes as a risk factor for distal sensory polyneuropathy. Both people with type 2 diabetes and people in the elderly general population were examined.

"In our study, we identified new biomarkers that indicate the risk of polyneuropathy. For the first time, we were also able to find indications that in addition to the innate immune system, the adaptive immune system could be involved in the development of the disease," explains Prof. Dr. med. Christian Herder, head of the study at the German Diabetes Center (DDZ).

"These findings could open new therapeutic perspectives. The goal could be to influence the immune system accordingly and thus ultimately prevent the development or progression of neuropathy, "adds neurodiabetologist Prof. Dr. med. Dan Ziegler, Deputy Director of the Institute for Clinical Diabetology at DDZ.

The study included 513 men and women of population-based KORA (Cooperative Health Research in the Augsburg region) F4 / FF4 cohort aged 62 to 81 years who had no distal sensory polyneuropathy at baseline.

Of these, 127 individuals developed a DSPN during the 6.5-year follow-up period. Serum levels of 71 total biomarkers of inflammation were measured using the new proximity extension assay technology. The serum level of 26 of these 71 biomarkers was higher in subjects who developed polyneuropathy during the study than in those who did not have polyneuropathy. Higher concentrations of six biomarkers were associated with the DSPN risk. 

The chemokines showed neurotoxic effects in a cell culture model,  indicating their involvement in the development of neuropathy. When the data for these six biomarkers was added to a clinical risk model, the predictive power of the model improved significantly. 

Further pathway analysis indicated that several cell types of innate and adaptive immunity are likely to be involved in the development of DSPN.

Overall, this study revealed novel associations between biomarkers of inflammation and the risk of polyneuropathy and provided indications that point to a complex interaction of innate and adaptive immunity in the development of polyneuropathy.

This study contributes new insights into the role of inflammatory processes in the development of distal sensory polyneuropathy, both in elderly and non-type 2 diabetes. Future studies may focus on the role of immune cells, to help determine whether inflammatory processes can be modulated to prevent and treat distal sensory polyneuropathy.

This article has been republished from materials provided by the German Center for Diabetes Research. Note: material may have been edited for length and content. For further information, please contact the cited source.

Herder, C., Kannenberg, J. M., Carstensen-Kirberg, M., Strom, A., Bönhof, G. J., Rathmann, W., . . . Ziegler, D. (2018). A Systemic Inflammatory Signature Reflecting Crosstalk Between Innate and Adaptive Immunity Is Associated With Incident Polyneuropathy: KORA F4/FF4 Study. Diabetes. doi:10.2337/db18-0060