Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy

Abstract

Aims/hypothesis: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.

Methods: This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.

Results: DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA_1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.

Conclusions/interpretation: Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.

Keywords: Axonal damage; Biomarker; Demyelination; Diabetes; Diabetic neuropathy; Diabetic sensorimotor polyneuropathy; Distal sensorimotor polyneuropathy; Electrophysiological tests; Large fibre; Nerve conduction study; Nerve dysfunction; Nerve injury; Neurofilament light chain; Neurofilaments; Neurological biomarkers; Peripheral nervous system; Peripheral neuropathy; Quantitative sensory tests; Small fibre.

Fig. 1

Serum NFL according to DSPN status. The boxplots with jittered data points show the distribution of serum NFL according to DSPN status. The line that divides the box into two parts represents the median of the data. The top and bottom of the box show the upper (Q3) and lower (Q1) quartiles. The extreme line shows Q3+1.5×IQR to Q1−1.5×IQR. Serum NFL is expressed as NPX values