Associations of complement proteins and immunoglobulins with cognitive impairment in type 2 diabetes mellitus: a cross-sectional study

Type 2 diabetes mellitus (T2DM) is a global health concern associated with an increased risk of cognitive impairment. While the complement system and immunoglobulins, crucial components of the immune system, have been implicated in the pathogenesis of both T2DM and cognitive decline, their specific clinical associations remain unclear. This study aims to investigate the association between inflammatory markers, specific complement proteins, immunoglobulins, and cognitive impairment in T2DM patients. A cross-sectional study was conducted involving 242 participants aged over 40 years from the First Hospital of Hebei Medical University between March 2022 and April 2023. Participants were divided into the control ( n = 120), T2DM ( n = 45), and T2DM with cognitive impairment (T2DM&CI) ( n = 77) groups. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Blood samples were analyzed for fasting blood glucose, lipid profiles, complement proteins, and immunoglobulins. Statistical analyses included non-parametric tests, receiver operating characteristic (ROC) curve analysis, and linear and logistic regressions adjusted for covariates (age and gender). Significant differences were observed among the groups in cognitive function scores, blood glucose, lipid levels, and inflammatory markers, complement proteins, and immunoglobulins. The T2DM & CI group exhibited lower MoCA scores and higher total cholesterol (TC), complement factor B (CFB), and immunoglobulin E (IgE) levels compared to the T2DM group. Correlation analyses revealed that elevated CFB and IgA were negatively correlated with cognitive function, whereas IgM showed a positive correlation. Following covariate adjustment, CFB remained independently associated with the presence of cognitive impairment in T2DM patients. Cognitive impairment in T2DM is significantly associated with altered immune-inflammatory profiles, specifically alternative complement pathway activation (elevated CFB) and specific immunoglobulin shifts (increased IgA, decreased IgM). CFB represents a promising potential biomarker for the early identification of cognitive risk in T2DM patients.