Different Complement Activation Pathways Underly Cognitive Impairment and Type 2 Diabetes Mellitus Combined With Cognitive Impairment

BACKGROUND: The immune response and the complement system are associated with cognitive impairment and diabetes mellitus, respectively. Activation of the complement system in these diseases occurs mainly through either the classical pathway or the alternative pathway. However, the specific complement proteins involved in the development of the type 2 diabetes mellitus (T2DM) and cognitive impairment are still unclear. Here, we investigated complement proteins in serum from patients with T2DM, cognitive impairment, or both T2DM and cognitive impairment. OBJECTIVE: To investigate the levels of serum immune complement proteins in patients with T2DM, cognitive impairment, or T2DM combined with cognitive impairment and the associations between these complement proteins and risk factors for T2DM or cognitive impairment. METHODS: Clinical markers were collected from blood samples of 264 participants. Luminex multiplex assays were used to detect serum complement proteins. All statistical analyses were performed using Prism or R studio. RESULTS: There was a difference in serum levels of the complement proteins C1q, C3, C3b, and FH between the three different groups. Hyperglycemia was significantly correlated with elevated C3b or reduced C3, C1q, and FH. In addition, hyperlipidemia was positively correlated with elevated levels of C3, C4, C1q, and FH proteins. There was an association between C1q, C3, C4, and FH and β-pancreas cell function, whereas only FH was associated with insulin resistance. Higher serum C1q was significantly associated with an increased risk of cognitive impairment. CONCLUSION: Serum levels of complement proteins were closely associated with hyperglycemia and hyperlipidemia. We found that classical complement pathway activation mainly occurred in the cognitive impairment only group, whereas the alternative pathway may reflect T2DM and T2DM with cognitive impairment.