Serum Neurofilament Light Chain Levels and Neuropathy Severity in Diabetic Polyneuropathy (DPN-NFL)

March 14, 2026 updated by: Zeynep Karakuzu Güngör, Kanuni Sultan Suleyman Training and Research Hospital

Association Between Serum Neurofilament Light Chain (NfL) Levels and Neuropathy Severity, Balance Performance, and Fall Risk in Diabetic Polyneuropathy

Diabetic polyneuropathy (DPN) is one of the most common chronic complications of diabetes mellitus and is characterized by peripheral nerve damage caused by long-term hyperglycemia. Progressive sensory loss and impairment of proprioception may lead to balance disturbances, gait instability, and an increased risk of falls. Neurofilament Light Chain (NfL) has emerged as a potential biomarker of neuroaxonal injury in several neurological disorders.

The aim of this observational cross-sectional study is to investigate the relationship between serum Neurofilament Light Chain (NfL) levels and neuropathy severity, balance performance, and fall risk in patients with diabetic polyneuropathy. Neuropathy severity will be evaluated using the Michigan Neuropathy Screening Instrument (MNSI) and electrophysiological findings, while balance performance and fall risk will be assessed using the Berg Balance Scale and the Falls Efficacy Scale-International (FES-I).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Diabetic polyneuropathy (DPN) is one of the most common chronic microvascular complications of diabetes mellitus and is characterized by peripheral nerve damage associated with long-standing hyperglycemia. Several pathophysiological mechanisms including oxidative stress, accumulation of advanced glycation end products, activation of the polyol pathway, and microvascular dysfunction contribute to distal axonal degeneration. Clinically, DPN commonly presents with distal symmetric sensory loss in a "glove-and-stocking" distribution accompanied by symptoms such as numbness, paresthesia, burning sensation, and neuropathic pain.

As the disease progresses, impairment of vibration and proprioception may occur, leading to deterioration in postural control, balance disturbances, and gait instability. These changes may increase the risk of falls and negatively affect functional capacity and quality of life in patients with diabetes.

Neurofilament Light Chain (NfL) is a structural protein found in neuronal cytoskeleton and is released into the bloodstream following axonal injury. In recent years, serum NfL has been investigated as a potential biomarker reflecting neuroaxonal damage in various neurological diseases. However, limited evidence exists regarding the association between serum NfL levels and clinical manifestations of diabetic polyneuropathy.

The aim of this observational cross-sectional study is to evaluate the relationship between serum Neurofilament Light Chain (NfL) levels and neuropathy severity, balance performance, and fall risk in patients with diabetic polyneuropathy. The study will include patients with Type 2 diabetes mellitus who attend the Physical Medicine and Rehabilitation outpatient clinic.

Participants will be divided into two groups: patients with diabetic polyneuropathy (DPN+) and diabetic patients without neuropathy (DPN-). The diagnosis of diabetic polyneuropathy will be established based on clinical examination, the Michigan Neuropathy Screening Instrument (MNSI), and electrophysiological evaluation using nerve conduction studies. Peripheral nerve conduction studies will include evaluation of motor and sensory nerves of the lower extremities, particularly tibial, peroneal, and sural nerves.

Serum Neurofilament Light Chain (NfL) levels will be measured using venous blood samples obtained after overnight fasting. Blood samples will be centrifuged and serum will be stored at -80°C until analysis. NfL measurements will be performed using a validated ELISA-based immunoassay kit according to the manufacturer's instructions.

Clinical evaluation will include neuropathy severity assessment using the Michigan Neuropathy Screening Instrument (MNSI), balance performance assessment using the Berg Balance Scale, and fall risk assessment using the Falls Efficacy Scale-International (FES-I). These measurements will allow evaluation of the relationship between serum NfL levels and both clinical and functional parameters.

The primary objective of the study is to investigate whether serum NfL levels are associated with the presence of diabetic polyneuropathy. Secondary objectives include evaluating the relationship between serum NfL levels and neuropathy severity, balance performance, and fall risk.

Receiver Operating Characteristic (ROC) analysis will be used to determine the diagnostic performance of serum NfL levels in distinguishing patients with diabetic polyneuropathy. This study focuses on patients with electrophysiologically confirmed large-fiber diabetic polyneuropathy, and patients with suspected small-fiber neuropathy without electrophysiological abnormalities will not be included in the study.

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults with type 2 diabetes mellitus aged 30-75 years attending a Physical Medicine and Rehabilitation outpatient clinic, including patients with diabetic polyneuropathy and diabetic individuals without neuropathy serving as controls.

Description

Inclusion Criteria:

Inclusion Criteria Age between 30 and 75 years Diagnosis of Type 2 Diabetes Mellitus for at least 1 year Ability to understand and complete clinical assessments and questionnaires Willingness to participate and provide written informed consent

For the DPN+ group:

Presence of diabetic polyneuropathy confirmed by clinical examination, Michigan Neuropathy Screening Instrument (MNSI), and nerve conduction studies

For the DPN- group:

Type 2 diabetes mellitus without clinical or electrophysiological evidence of diabetic polyneuropathy

Exclusion Criteria:

  • Neuropathy due to causes other than diabetes (e.g., vitamin B12 deficiency, hypothyroidism, alcohol abuse, chemotherapy) Renal dysfunction (eGFR < 60 mL/min/1.73 m²) Active infection or malignancy Inflammatory or autoimmune neurological diseases Central nervous system disorders (e.g., stroke, multiple sclerosis) Lumbar radiculopathy or peripheral entrapment neuropathy Severe visual impairment or balance disorders affecting testing Pregnancy Cognitive impairment preventing completion of questionnaires Patients with isolated small fiber neuropathy without electrophysiological evidence of large fiber involvement

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Diabetic Polyneuropathy (DPN+)
Participants with Type 2 diabetes mellitus diagnosed with diabetic polyneuropathy based on clinical examination, the Michigan Neuropathy Screening Instrument (MNSI), and electrophysiological evaluation using nerve conduction studies.
Other: Blood Sample Collection and Clinical Assessment
Participants will undergo venous blood sample collection for measurement of serum Neurofilament Light Chain (NfL) levels. Blood samples will be obtained after overnight fasting, centrifuged, and serum samples will be stored at -80°C until analysis. Serum NfL levels will be measured using a validated ELISA-based immunoassay. In addition, clinical assessments including the Michigan Neuropathy Screening Instrument (MNSI), Berg Balance Scale, and Falls Efficacy Scale-International (FES-I) will be performed to evaluate neuropathy severity, balance performance, and fall risk.
Diabetic Control (DPN-)
Participants with Type 2 diabetes mellitus without clinical or electrophysiological evidence of diabetic polyneuropathy who will serve as the control group.
Other: Blood Sample Collection and Clinical Assessment
Participants will undergo venous blood sample collection for measurement of serum Neurofilament Light Chain (NfL) levels. Blood samples will be obtained after overnight fasting, centrifuged, and serum samples will be stored at -80°C until analysis. Serum NfL levels will be measured using a validated ELISA-based immunoassay. In addition, clinical assessments including the Michigan Neuropathy Screening Instrument (MNSI), Berg Balance Scale, and Falls Efficacy Scale-International (FES-I) will be performed to evaluate neuropathy severity, balance performance, and fall risk.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Neurofilament Light Chain Levels
Time Frame: At baseline
To evaluate the association between serum Neurofilament Light Chain (NfL) levels and the presence and severity of diabetic polyneuropathy assessed by the Michigan Neuropathy Screening Instrument (MNSI) and electrophysiological findings.
At baseline
Balance Performance
Time Frame: Baseline
To evaluate the relationship between serum Neurofilament Light Chain (NfL) levels and balance performance measured using the Berg Balance Scale in patients with diabetic polyneuropathy.
Baseline
Fear of Falling
Time Frame: Baseline
To assess the association between serum Neurofilament Light Chain (NfL) levels and fear of falling using the Falls Efficacy Scale-International (FES-I).
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kanuni Sultan Suleyman Training and Research Hospital

Investigators

  • Principal Investigator: Zeynep Karakuzu Güngör, M.D, Kanuni Sultan Suleyman Training and Research Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 25, 2026

Primary Completion (Estimated)

April 30, 2026

Study Completion (Estimated)

May 15, 2026

Study Registration Dates

First Submitted

March 14, 2026

First Submitted That Met QC Criteria

March 14, 2026

First Posted (Actual)

March 18, 2026

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 14, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DPN-NFL-2026

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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