Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis

People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia. Systemic inflammation has been proposed as a common risk factor. This study aimed to summarize the clinical data pertaining to peripheral blood inflammatory markers. We identified original peer-reviewed articles reporting blood inflammatory marker concentrations in groups of people with a T2DM diagnosis who have cognitive impairment (CI; including mild cognitive impairment, Alzheimer's disease, vascular cognitive impairment) vs. normal cognition (NC). Between-group standardized mean differences (SMD) were summarized in random effects meta-analyses. From 2108 records, data were combined quantitatively from 40 studies. Concentrations of interleukin-6 (IL-6; N-CI/N-NC = 934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z(5) = 2.15, p = 0.03; I-2 = 98.08%), C-reactive protein (CRP; N-CI/N-NC = 1610/4363, SMD 0.80 [0.50, 1.11], Z(14) = 5.25, p < 0.01; I-2 = 94.59%), soluble vascular cell adhesion molecule-1 (sVCAM-1; N-CI/N-NC = 104/1063, SMD 1.64 95% confidence interval [0.21, 3.07], Z(2) = 2.25, p = 0.02; I-2 = 95.19%), and advanced glycation end products (AGEs; N-CI/N-NC = 227/317, SMD 0.84 95% confidence interval [0.41, 1.27], Z(2) = 3.82, p < 0.01; I-2 = 81.07%) were higher among CI groups compared to NC. Brain derived neurotmpic factor (BDNF) concentrations were significantly lower in CI compared to NC (N-CI/N-NC = 848/2063, SMD -0.67 95% confidence interval [-0.99, -0.35], Z(3) = -4.09, p < 0.01; I-2 = 89.20%). Cognitive impairment among people with T2DM was associated with systemic inflammation and lower BDNF concentrations. These inflammatory characteristics support an increased inflammatory-vascular interaction associated with cognitive impairment in T2DM. PROSPERO (CRD42020188625).

Automated summary

People with type 2 diabetes mellitus are at increased risk of mild cognitive impairment and dementia, with systemic inflammation proposed as a common risk factor. This study found that cognitive impairment in T2DM patients was associated with higher levels of inflammatory markers like IL-6, CRP, sVCAM-1, and AGEs, as well as lower levels of BDNF. These findings suggest an inflammatory-vascular interaction contributing to cognitive impairment in T2DM.