MD, PhD Laura L. Määttä and her colleagues have uncovered the possibility of using the protein neurofilament light chain as a biomarker for detecting and monitoring diabetic neuropathy.

A PhD project from Aarhus University has investigated the biomarker potential of the protein neurofilament light chain (NfL) for detecting and monitoring diabetic polyneuropathy in people with type 2 diabetes.

Some of the findings from the project were published in the article Longitudinal Change in Serum Neurofilament Light Chain in Type 2 Diabetes and Early Diabetic Polyneuropathy: ADDITION-Denmark in Diabetes Care earlier this year.

We spoke to the lead author, MD, PhD and DDEA grant recipient Laura L. Määttä about the study.

The Importance of Early Detection

Neuropathy is one of the most common complications of diabetes, affecting around half of all people with diabetes. Despite diabetic neuropathy being so common, there are currently no direct treatments for it, and it often goes undetected.

With her PhD project, Laura L. Määttä wanted to explore possible ways to change this.

“We wanted to see if we could find a method to easily measure and quantify nerve damage in people with diabetes. Firstly, to focus the attention of physicians and patients on diabetic neuropathy and secondly, to prevent the nerve damage from worsening. As there are no treatments for diabetic neuropathy yet, early detection and prevention is crucial,” says Laura L. Määttä.

NfL Levels Linked to Diabetic Neuropathy

Laura L. Määttä and her colleagues investigated the biomarker potential of a protein called neurofilament light chain (NfL) in the context of diabetic neuropathy.

“Neurofilament light chain is a structural protein specifically found in nerves. It is part of the building blocks that allow the neuronal cell to maintain its structure. NfL has gained massive attention as a marker of central nervous system disease but rather little is known about its utility in the context of peripheral neuropathies such as diabetic neuropathy. So, we wanted to determine whether NfL could be used to measure peripheral nerve damage in the blood of people with diabetes,” explains Laura L. Määttä.

The PhD project combined analysis of biobank material and clinical- and registry-based data to illustrate cross-sectional and longitudinal associations between NfL and the presence, severity, and development of diabetic neuropathy. The current study focused on the longitudinal development of NfL levels over time and was the first to investigate this in adults with type 2 diabetes.

“We saw that the levels of NfL increased more over time in people with diabetes who developed diabetic neuropathy compared to those who didn’t develop neuropathy. This could indicate that NfL is a potential biomarker for monitoring the development of neuropathy, as well as help with testing the efficacy of new treatments for diabetic neuropathy, Surprisingly, NfL also increased at levels above the normal age-induced NfL increase in those who didn’t develop neuropathy, suggesting that diabetes, or factors associated with diabetes, influence NfL levels even in relatively early and well-controlled type 2 diabetes,” says Laura L. Määttä.

A Need for Simplifying Measuring Methods

The current methods to confirm and monitor neuropathy are too complex to be used in an everyday clinical setting. This problem could potentially be solved using NfL as a biomarker, as the levels are measured in blood samples.

“Measuring neuropathy today, or more specifically – nerve damage and dysfunction, requires access to special equipment and specialised personnel, and it is a laborious process. Screening-wise we have questionnaires, and in a general clinical setting, we base the diagnosis of diabetic neuropathy on the patient’s symptoms and bedside tests, such as touch and vibration sensation. This might not always catch the early stages of neuropathy development and does not allow us to quantify the degree of nerve damage. When measuring NfL levels, it is all done using blood samples, as it is a protein released from nerves into the blood, hence reflecting the status of nerve fibres. This could potentially make the process of monitoring neuropathy easier,” explains Laura L. Määttä.

Next Steps and Future Research

Laura L. Määttä hopes to see the research into NfL and other neuronal biomarkers in diabetic neuropathy taken to the next step, but for this, new studies and new data are needed.

“We looked back in time, so to speak, with analysis of biobank material from existing cohorts, so prospective studies coupling individual NfL trajectories with repeated evaluation of nerve function from the time of diabetes diagnosis are needed to clarify the viability of the biomarker in a clinical setting. The potential is there, but more studies are needed,” says Laura L. Määttä.

In September, NeuroDiab, the association dedicated to advancing knowledge of diabetic neuropathy, will hold its Annual Meeting in Rome. Laura L. Määttä has been invited to speak at the meeting under the title ‘Critical reappraisal of nerve biomarkers’.

“The talk will focus on our knowledge of NfL and other nerve-specific proteins as biomarkers for neuropathy. I will give a short overview of this, the status of the research and the current clinical applicability. It’s such an honour to have been invited to speak at the meeting, and I very much look forward to it,” says Laura L. Määttä.

Contact

Laura L. Määttä
MD, PhD
Danish Pain Research Center
Department of Clinical Medicine, Aarhus University
llm@clin.au.dk / laumaa@rm.dk

Publication

Longitudinal Change in Serum Neurofilament Light Chain in Type 2 Diabetes and Early Diabetic Polyneuropathy: ADDITION-Denmark

Laura L. Määttä, Signe T. Andersen, Tina Parkner, Claus V.B. Hviid, Lasse Bjerg, Mustafa A. Kural, Morten Charles, Esben Søndergaard, Jens Kuhle, Hatice Tankisi, Daniel R. Witte, Troels S. Jensen

Diabetes Care (March 2024)

DOI: https://doi.org/10.2337/dc23-2208