The Association of Prosaposin with Type 2 Diabetes Mellitus and Lower-Limb Motor Nerve Conduction Abnormalities

Background/Objectives: Prosaposin (PSAP) is a multifunctional protein involved in sphingolipid metabolism and neuroprotection. This study investigated the association between serum PSAP levels and type 2 diabetes mellitus (T2DM) and explored the association between PSAP and lower-limb motor nerve conduction abnormalities in patients with T2DM. Methods: This single-center cross-sectional study included 172 participants (48 normal controls and 124 patients with T2DM). Serum PSAP was measured by ELISA. Among patients with T2DM, 112 underwent nerve conduction studies to assess lower-limb motor nerve conduction abnormalities. Logistic regression, Firth penalized logistic regression, and RCS analyses were performed. Exploratory mediation analysis with 5000 bootstrap resamples evaluated the indirect effect involving glycated hemoglobin A1c (HbA1c) in the association between PSAP and T2DM. Results: Serum PSAP levels were higher in patients with T2DM than in normal controls (p < 0.001). The association between lnPSAP and T2DM remained significant after adjustment for age, sex, systolic blood pressure, BMI, and total cholesterol (p = 0.008), but was attenuated and no longer significant after further adjustment for HbA1c. Exploratory mediation analysis identified a significant indirect-effect estimate involving HbA1c (p < 0.001), warranting cautious interpretation given the cross-sectional design and the role of HbA1c in T2DM diagnosis. For lower-limb motor nerve conduction abnormalities, lnPSAP was significantly associated in univariable analysis (p = 0.044), but not after multivariable adjustment (p = 0.157), consistent with the Firth penalized logistic regression and RCS analyses. Conclusions: Serum PSAP levels were elevated in patients with T2DM, although the association was substantially attenuated after further adjustment for HbA1c. The exploratory mediation findings do not establish a causal pathway. The association between PSAP and lower-limb motor nerve conduction abnormalities remained inconclusive after multivariable adjustment. Further longitudinal studies are needed to clarify these associations.