Associations between complexity of glucose time series and cognitive function in adults with type 2 diabetes

Aims: To characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction, and further investigate the associations between the most significant indicator and cognitive function, along with related cerebral alterations.Materials and Methods: We performed a cross-sectional study in 449 subjects with type 2 diabetes who completed continuous glucose monitoring and cognitive assessments. Of these, 139 underwent functional magnetic resonance imaging to evaluate cerebral structure and olfactory neural circuit alterations. Relative weight and Sobol's sensitivity analyses were employed to characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction.Results: Complexity of glucose time series index (CGI) was found to have a more pronounced association with mild cognitive impairment (MCI) compared to glycated haemoglobin, time in range, and standard deviation. The proportion and multivariable-adjusted odds ratios (ORs) for MCI increased with descending CGI tertile (Tertile 1: reference group [>= 4.0]; Tertile 2 [3.6-4.0] OR 1.23, 95% confidence interval [CI] 0.68-2.24; Tertile 3 [<3.6] OR 2.27, 95% CI 1.29-4.00). Decreased CGI was associated with cognitive decline in executive function and attention. Furthermore, individuals with decreased CGI displayed reduced olfactory activation in the left orbitofrontal cortex (OFC) and disrupted functional connectivity between the left OFC and right posterior cingulate gyrus. Mediation analysis demonstrated that the left OFC activation partially mediated the associations between CGI and executive function.Conclusion: Decreased glucose complexity closely relates to cognitive dysfunction and olfactory brain activation abnormalities in diabetes.