Low Plasma Leptin and High Soluble Leptin Receptor Levels Are Associated With Mild Cognitive Impairment in Type 2 Diabetic Patients

Background: Metabolic disturbances, such as hyperglycemia, hyperlipidemia, and obesity, are thought to be risk factors for Alzheimer's disease. Objective: This study aimed to investigate whether adipokine leptin and soluble leptin receptor (sOBR) levels are correlated with mild cognitive impairment (MCI) and metabolic status of the patients of type 2 diabetes mellitus (T2DM). Methods: Total of 169 T2DM patients were recruited and divided according to the Montreal Cognitive Assessment (MoCA) score. Their cognition and metabolic parameters were extensively assessed. Plasma leptin and sOBR levels were determined by RIA and ELISA, respectively. Free leptin index (FLI) was calculated. Results: Of 124 enrolled T2DM patients, 61 were diagnosed with MCI (MoCA < 26). In MCI group and female subgroup, leptin levels and FLI were significantly lower and sOBR concentrations were higher when compared with their respective health cognition controls (all p < 0.05). Leptin levels and FLI were positively associated with the most cognitive domains and their Waist-to-Hip Ratio (WHR), a traditional index of central obesity. Leptin, sOBR, and WHR were independent variables of MCI in all individuals (all p < 0.05). For the females, MoCA was also positively correlated with leptin (β = 0.893, p < 0.001) and negatively correlated with WHR (β = −0.363, p = 0.014). Leptin was positively correlated only with WHR (β = 0.441, p = 0.025). Conclusions: This study showed that a high level of leptin and low level of sOBR are associated with the improved cognitive function in T2DM patients and more significantly in female individuals, while WHR, as an indicator of the visceral obesity, contributes to cognitive deficits. Trial registration: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536.