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Background: In addition to glucose metabolism, adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) has been proposed as a multifunctional protein involved in insulin resistance. Insulin resistance always occurs before the onset of type 2 diabetes mellitus (T2DM) and damages the cognition of T2DM patients very early.Objective: We aimed to investigate the role and potential clinical value of Nampt in early cognitive decline of T2DM.Methods: A total of 195 Chinese T2DM patients were enrolled and divided into a mild cognition impairment (MCI) group and a healthy cognition group according to Montreal Cognitive Assessment (MoCA) score. Their cognitive function was extensively assessed. The plasma level of Nampt was measured via enzyme-linked immunosorbent assay.Results: In the MCI group (n = 78, MoCA < 26), the plasma level of Nampt was significantly higher than the controls (p < 0.01). After adjusting for age, sex, and level of education, Nampt levels were negatively associated with most of the cognitive domains forecasting hypomnesia (all p < 0.007). Nevertheless, hierarchical regression analysis further revealed that Nampt was an independent risk factor of MCI in Chinese T2DM patients (all p < 0.05), including Logic Memory Test (β= -0.31, p < 0.01), Auditory Verbal Learning Test delayed recall (β= -0.26, p < 0.01), and so on, which represent memory function. Correlation analysis showed that Nampt related to insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), and lipid levels (all p < 0.05).Conclusions: We found that higher plasma level of Nampt presages memory dysfunction in MCI in Chinese T2DM patients. Further studies are necessary to confirm its scanning and prognosis prediction value of the disease clinically. [ABSTRACT FROM AUTHOR]