European journal of medical research · 2026
Development and validation of a risk prediction model integrating WWI and lipocalin-2 for cognitive impairment in patients with type 2 diabetes.
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Liu Kunyu, Niu Tong, Zhou Junru, Sun Ruoyu, Wang Shaohua, Yuan Yang
Аннотация
OBJECTIVE: To evaluate the associations of the weight-adjusted waist index (WWI) and plasma lipocalin-2 (LCN2) with Montreal Cognitive Assessment (MoCA) -defined mild cognitive impairment (MCI) and to develop a risk prediction model in patients with type 2 diabetes mellitus (T2DM).
METHODS: In this cross-sectional study, 410 patients were included. Anthropometric parameters, metabolic indices, plasma LCN2 levels, and neuropsychological test data were collected. Participants were randomly divided into a training cohort (70%) and a validation cohort (30%). Cognitive function was assessed using neuropsychological tests. MCI was defined based on MoCA scores (< 26). Predictors selected using LASSO regression were subsequently entered into multivariable logistic models. Model performance-including discrimination, calibration, and clinical utility-was evaluated in both cohorts.
RESULTS: WWI and plasma LCN2 levels were significantly higher in participants with MCI than in those with normal cognition (both P < 0.01). After adjustment for demographic and metabolic factors, WWI (OR = 1.753, 95% CI 1.337-2.299) and plasma LCN2 (per SD increase; OR = 1.680, 95% CI 1.255-2.248) remained independently associated with MCI. A multivariable model incorporating age, gender, education, WWI, and LCN2 demonstrated satisfactory discrimination [area under the curve (AUC) = 0.745 (95% CI 0.688-0.802) in the training cohort and 0.774 (95% CI 0.693-0.854) in the validation cohort], with acceptable calibration in both cohorts. The model showed higher discrimination than models based on individual predictors alone.
CONCLUSION: WWI and LCN2 are independently and jointly associated with MCI in T2DM, and their integration may improve risk stratification for cognitive impairment. These obesity- and inflammation-related markers may serve as complementary indicators to support cognitive risk assessment in diabetes care.
METHODS: In this cross-sectional study, 410 patients were included. Anthropometric parameters, metabolic indices, plasma LCN2 levels, and neuropsychological test data were collected. Participants were randomly divided into a training cohort (70%) and a validation cohort (30%). Cognitive function was assessed using neuropsychological tests. MCI was defined based on MoCA scores (< 26). Predictors selected using LASSO regression were subsequently entered into multivariable logistic models. Model performance-including discrimination, calibration, and clinical utility-was evaluated in both cohorts.
RESULTS: WWI and plasma LCN2 levels were significantly higher in participants with MCI than in those with normal cognition (both P < 0.01). After adjustment for demographic and metabolic factors, WWI (OR = 1.753, 95% CI 1.337-2.299) and plasma LCN2 (per SD increase; OR = 1.680, 95% CI 1.255-2.248) remained independently associated with MCI. A multivariable model incorporating age, gender, education, WWI, and LCN2 demonstrated satisfactory discrimination [area under the curve (AUC) = 0.745 (95% CI 0.688-0.802) in the training cohort and 0.774 (95% CI 0.693-0.854) in the validation cohort], with acceptable calibration in both cohorts. The model showed higher discrimination than models based on individual predictors alone.
CONCLUSION: WWI and LCN2 are independently and jointly associated with MCI in T2DM, and their integration may improve risk stratification for cognitive impairment. These obesity- and inflammation-related markers may serve as complementary indicators to support cognitive risk assessment in diabetes care.