Prevalence of mild cognitive impairment in type 2 diabetes mellitus is associated with serum galectin‐3 level

Abstract

Aims/Introduction Galectin‐3 (Gal3) contributes to insulin resistance, inflammation and obesity, the three risk factors for mild cognitive impairment (MCI) in type 2 diabetes mellitus patients. Materials and methods A total of 134 hospitalized type 2 diabetes mellitus patients were assessed by the Montreal Cognitive Assessment method, and divided into 65 MCI and 69 controls. Levels of variables, Gal3 and Aβ42, were investigated in relation with cognitive function in both type 2 diabetes mellitus patients with MCI and high‐fat diet/streptozotocin induced type 2 diabetes mellitus rats. Results Significantly higher levels of serum Gal3 and lower levels of plasma Aβ42 (all P < 0.05) were found in the MCI type 2 diabetes mellitus group as compared with the non‐MCI type 2 diabetes mellitus control. Partial correlation analysis showed that Gal3 is negatively correlated with both MMSE score (r = −0.51, P < 0.01) and Montreal Cognitive Assessment score (r = −0.47, P < 0.001) after adjustment for glycated hemoglobin, homoeostasis model assessment of insulin resistance and Aβ42 in all type 2 diabetes mellitus patients, with a stronger effect seen in the MCI type 2 diabetes mellitus group after further analysis with MCI strata. A simple logistic regression model showed that Gal3 and Aβ42 are significantly associated with MCI type 2 diabetes mellitus patients after adjustment with the covariates sex, age, body mass index, glycated hemoglobin, homoeostasis model assessment of insulin resistance and antidiabetic drugs. Serum and brain Gal3 levels were significantly increased in high‐fat diet/streptozotocin diabetic rats, which correlate to the impairment of learning and memory ability. Gal3 inhibitor modified citrus pectin decreased serum and brain Gal3 levels in diabetic rats, accompanied by the amelioration of learning and memory impairment. Conclusions Gal3 might be associated with cognitive impairment in type 2 diabetes mellitus, and serum Gal3 level might be a new risk factor of MCI in type 2 diabetes mellitus patients.

Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus

“…Hyperglycemia is a well-recognized risk factor of cognition decline. Uncontrolled HbA1c levels were detected in our previous studies [ 34 – 36 ] and other works [ 37 ]. Although HbA1c levels were not significantly different, higher HbA1c levels were measured in patients with MCI than in patients without MCI in the present study.…”

Galectin-3: a key player in microglia-mediated neuroinflammation and Alzheimer's disease

“…Recently, research has focused on cerebrovascular and neurodegenerative chronic complications of diabetes, such as diabetes-associated cognitive impairment [ 109 ]. In our previous study, we found that serum Gal-3 was significantly higher in T2DM patients with mild cognitive impairment (MCI) than in T2DM controls, even after adjustment for multiple potential confounders [ 110 ]. Similarly, Gal-3 levels in the serum and brain were increased in diabetic rats and were associated with neuroinflammation, oxidative stress, learning and memory impairment, while administration of MCP could reverse these outcomes [ 105 ].…”

Galectins in Cancer and the Microenvironment: Functional Roles, Therapeutic Developments, and Perspectives

“…In agreement with other reports, the authors also showed that GCS-100, an antagonist of Gal-3, induced cancer cell death [ 190 , 191 , 192 ], boosted tumor-infiltrating T lymphocyte secretion of IFN-gamma [ 143 ], and increased prostate cancer sensitivity to cisplatin [ 193 ]. Similarly, an effect was observed in response to modified citrus pectin (MCP) on cancer [ 67 , 95 , 194 , 195 ]; however, MCP can also be used for other Gal-related disease treatments, such as decreasing Gal-3 levels in type 2 diabetes [ 196 ], decreasing doxorubicin-induced cardiovascular diseases [ 197 ], ameliorating cardiac dysfunction [ 198 ], and improving ischemic heart failure [ 199 ]. In addition, the calixarene derivative compound “OTX-008” was designed as a Gal-1 inhibitor [ 200 ].…”