Clinical Utility of Serum Cystatin C in Predicting Diabetic Distal Sensorimotor Polyneuropathy

Background: Approximately half of patients with diabetes mellitus (DM) develop diabetic distal symmetric sensorimotor polyneuropathy (DM-DSPN), yet no reliable biomarkers for its early detection exist. This study assesses cystatin C (CysC), a naturally occurring protein, in diabetic persons with and without large-fiber DM-DSPN. Methods: This study involved persons with diabetes (HbA1c > 6.5%) visiting specialized diabetic clinics at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia. Clinical features, laboratory data, nerve conduction findings, and serum CysC levels were assessed. DM-DSPN was diagnosed if signs of large nerve fiber impairment were present in the lower extremity in a symmetric and length-dependent pattern. Participants were designated as diabetic with or without large-fiber DSPN (+DM/+DSPN and +DM/-DSPN, respectively) based on validated composite scores of nerve conduction attributes. Results: A total of 52 persons with diabetes were included for analysis (24 with +DM/+DSPN and 28 with +DM/-DSPN). One participant had type 1 DM; all remaining participants had type 2 DM. In multivariate regression, serum CysC ≥ 0.88 mg/L was significantly associated with DM-DSPN. Serum CysC was significantly associated with peroneal and ulnar compound muscle action potential amplitudes (p-value = 0.003 and p-value = 0.03, respectively) and peroneal and tibial motor nerve conduction velocities (p-value = 0.009 and p-value = 0.0003, respectively). Conclusions: Serum CysC levels > 0.9 mg/L are associated with DM-DSPN (86% sensitivity and 81% specificity), independently of HbA1c or GFR. Serum CysC is also associated with peroneal and ulnar compound muscle action potential amplitudes and peroneal and tibial motor nerve conduction velocities. Larger studies are needed to determine the role of CysC as a potential biomarker of DM-DSPN.