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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. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between serum exosomal miR-9-3p levels and mild cognitive impairment (MCI) in patients with type 2 diabetes. Methods This cross-sectional study collected type 2 diabetic patients who visited the Endocrinology Department of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from February 2016 to March 2021. Cognitively normal healthy controls matched for age, sex, and education level were recruited. Levels of serum exosomal miR-9-3p, fasting C-peptide (FCP), fasting insulin and fasting plasma glucose (FPG) were measured. The homeostasis model assessment for insulin resistance index (HOMA-IR) was calculated. Mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and 3.0 T high-resolution magnetic resonance imaging scan were performed. According to the diagnostic criteria of MCI, patients with type 2 diabetes were divided into cognitively normal group and MCI group. One-way ANOVA was used to compare serum exosomal miR-9-3p levels between groups. Relationships between serum exosomal miR-9-3p and cognitive function or grey matter volume were assessed using partial correlation analysis. Associations between serum exosomal miR-9-3p and risk of MCI were analyzed using logistic regression analysis. Receiver operating characteristic curves were used to assess the predictive value of serum exosomal miR-9-3p. Results Seventy subjects were included in the study. There were 23 healthy controls, 35 cognitively normal type 2 diabetics, and 12 type 2 diabetics with MCI. Serum exosomal miR-9-3p levels were significantly higher in type 2 diabetics with MCI [(2 111.9±722.7) fM] than in cognitively normal type 2 diabetics [(1 264.6±699.3) fM] or healthy controls [(586.3± 275.3) fM] (P<0.001). After adjusting for age, sex and years of education, serum exosomal miR-9-3p was negatively associated with MMSE score, MoCA score, and grey matter volume (r=-0.390, -0.322, and -0.549, respectively, all P<0.05) in patients with type 2 diabetes. Serum exosomal miR-9-3p was an independent influencing factor for MCI (OR=1.241, 95%CI 1.033-1.490, P=0.021) after adjusting for age, sex, years of education, FCP and HOMA-IR. The area under the receiver operating characteristic curve was 0.824. Sensitivity and specificity were 91.7% and 68.6%, respectively. Conclusion Increased levels of serum exosomal miR-9-3p are associated with an increased risk of mild cognitive impairment in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]