Abstract
BackgroundThe 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.ObjectiveTo 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.MethodsClinical 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.ResultsThere 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.ConclusionSerum 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.
Highlights
Diabetes mellitus is ranked as one of the top 10 causes of death worldwide (Chatterjee et al, 2017)
We classified participants into four groups: normal (n = 70), Type 2 diabetes mellitus (T2DM) only (n = 51), cognitive impairment only (n = 84) and T2DM combined with cognitive impairment (n = 59), predominantly according to fasting blood glucose levels and scores on either Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MOCA)
The present study found that the serum levels of C3b were highest in the comorbid T2DM group, indicating that the activation of the alternative pathway may play a key role in T2DM-related cognitive disorder
Summary
Diabetes mellitus is ranked as one of the top 10 causes of death worldwide (Chatterjee et al, 2017). Individuals with T2DM are at a higher risk than non-diabetic individuals of developing dementia and cognitive impairment, such as Alzheimer’s disease (Biessels et al, 2006, 2014; Strachan et al, 2011; McCrimmon et al, 2012; Biessels and Reagan, 2015; Biessels and Despa, 2018), and between 10 and 15% of dementia cases worldwide may be attributed to T2DM (Biessels and Reagan, 2015). A cohort study found that low baseline plasma levels of complement C3 were associated with a high risk of Alzheimer’s disease (Rasmussen et al, 2018a) Another clinical study showed that serum levels of C1q, another complement protein, were significantly higher in major depressive disorder patients than in controls (Yao and Li, 2020). We investigated complement proteins in serum from patients with T2DM, cognitive impairment, or both T2DM and cognitive impairment
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