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 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.