Exploring galectin-3's role in predicting mild cognitive impairment in type 2 diabetes and its regulation by miRNAs

This study aimed to investigate the role of galectin-3 (Gal-3; coded by LGALS3 gene), as a biomarker for MCI in T2DM patients and to develop and validate a predictive nomogram integrating galectin-3 with clinical risk factors for MCI prediction. Additionally, microRNA regulation of LGALS3 was explored.

The study employed a cross-sectional design. A total of 329 hospitalized T2DM patients were recruited and randomly allocated into a training cohort (n = 231) and a validation cohort (n = 98) using 7:3 ratio. Demographic data and neuropsychological assessments were recorded for all participants. Plasma levels of galectin-3 were measured using ELISA assay. We employed Spearman's correlation and multivariable linear regression to analyze the relationship between galectin-3 levels and cognitive performance. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for MCI in T2DM patients. Based on these analyses, a predictive nomogram incorporating galectin-3 and clinical predictors was developed. The model's performance was evaluated in terms of discrimination, calibration, and clinical utility. Regulatory miRNAs were identified using bioinformatics and their interactions with LGALS3 were confirmed through qRT-PCR and luciferase reporter assays.

Galectin-3 was identified as an independent risk factor for MCI, with significant correlations to cognitive decline in T2DM patients. The developed nomogram, incorporating Gal-3, age, and education levels, demonstrated excellent predictive performance with an AUC of 0.813 in the training cohort and 0.775 in the validation cohort. The model outperformed the baseline galectin-3 model and showed a higher net benefit in clinical decision-making. Hsa-miR-128-3p was significantly downregulated in MCI patients, correlating with increased Gal-3 levels, while Luciferase assays confirmed miR-128-3p's specific binding and influence on LGALS3.

Our findings emphasize the utility of Gal-3 as a viable biomarker for early detection of MCI in T2DM patients. The validated nomogram offers a practical tool for clinical decision-making, facilitating early interventions to potentially delay the progression of cognitive impairment. Additionally, further research on miRNA128's regulation of Gal-3 levels is essential to substantiate our results.