Reduced Serum Levels of Klotho are Associated with Mild Cognitive Impairment in Patients with Type 2 Diabetes Mellitus

Abstract

Objective The study objective was to investigate the serum levels of Klotho in patients with type 2 diabetes mellitus (T2DM) who had moderate cognitive impairment (MCI) and those without MCI and to determine its prediction of MCI in older patients with T2DM. Methods Patients with diabetes were examined for MCI in 292 cases (using the Montreal Cognitive Assessment: MoCA score). Biomarkers and biochemical parameter data were accumulated. Results Comparing T2DM patients with MCI (91 patients) and without MCI (101 patients), patients with MCI considerably reduced serum Klotho levels were observed. In all 292 hospitalized patients, serum Klotho levels were negatively correlated with age (r=−0.184, P=0.002), body mass index (BMI) (r=−0.151, P=0.010), glycosylated hemoglobin (HbA1c) (r=−0.197, P=0.001), creatinine (r=−0.178, P=0.002), and C-reactive protein (CRP) (r=−0.319, P<0.001). On the other hand, it is positively correlated with education (r=0.319, P<0.001) and high-density lipoprotein cholesterol (HDL-C) (r=0.272, P<0.001). Considering the findings of the multivariate logistic regression models, patients with type 2 diabetes who had reduced levels of serum Klotho (OR=0.987, 95% CI=0.980–0.994; P<0.001), lower HDL-C, increased levels of HbA1c, creatinine, and CRP, and limited years of formal education and a longer duration of T2DM, increase the risk of developing MCI. Conclusion The results showed that diabetic patients with MCI have lower serum Klotho levels than diabetic patients without MCI. It might be possible to do a more extensive population-based prospective investigation to confirm the correlation between serum Klotho levels and cognitive impairment or dementia.

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho

“…To our knowledge, this is the first population-based study discussing the involvement of klotho in glucose-associated cognitive impairment. The findings align with emerging preclinical evidence indicating neuroprotective properties of klotho against neuronal insulin resistance and oxidative stress (13)(14)(15). Our study extends the current literature by identifying klotho as a key intermediary linking circulatory glucose disturbance to cognitive aging in a general elderly population.…”

“…Klotho increases insulin receptor affinity and enhances insulin sensitivity ( 11 ). Moreover, klotho exerts neuroprotective effects ( 12 , 13 ). Hence, klotho may mediate the detrimental effects of glucose on cognition, but relevant evidence is scarce.…”