Cognitive impairment and the development of Alzheimer’s disease are recognized risk factors in type 2 diabetes mellitus. Research continues to link metabolic dysregulation and specifically, insulin resistance, with Alzheimer’s disease and other forms of cognitive loss.
Galectin-3 Fuels Diabetes and Cognitive Decline
Emerging research into the beta-galactoside binding protein Galectin-3 (Gal-3) offers an important look into the relationships between elevated Gal-3, glucose dysregulation, diabetes and cognitive impairment. Importantly, findings point to Gal-3 as an upstream driver of metabolic dysfunction and cognitive decline including Alzheimer’s, highlighting Gal-3 as a promising therapeutic target in these and other conditions.
Accumulating data shows that Gal-3 inhibition is a novel strategy to address cognitive decline and is achievable with Modified Citrus Pectin (MCP), the most-researched Gal-3 blocker available today.
One study, published in Journal of Diabetes Investigation, includes in vivo and human clinical data demonstrating the role of Gal-3 in neuroinflammation resulting in cognitive decline among diabetic patients and subjects. Inhibition of Gal-3 by MCP helped prevent cognitive loss and supported against the development of Alzheimer’s disease in a diabetic animal model.
Study Design
- 134 hospitalized T2DM patients were assessed by the Montreal Cognitive Assessment (MoCA) method and. divided into 65 MCI and 69 controls.
- Levels of Gal-3 were investigated in relationship with cognitive function in both T2DM patients with MCI and high-fat diet (HFD)/streptozotocin (STZ) induced T2DM rats; some of the rats also received MCP (100 mg/kg/day).
Study Results
- A higher level of serum Gal-3 was found in MCI T2DM group compared to non-MCI T2DM control.
- Partial correlation analysis showed that Gal-3 was negatively correlated with both Mini-Mental State Examination (MMSE) score (r = -0.51) and MoCA score (r = -0.47), with stronger effect seen in MCI T2DM group after further analysis with MCI strata.
- Simple logistic regression model demonstrated that Gal-3 was associated with MCI T2DM patients.
- Serum and brain Gal-3 levels were significantly increased in HFD/ STZ diabetic rats, which correlated to the impairment of learning and memory ability.
- MCP decreased serum and brain Gal-3 levels in diabetic rats, accompanied by the amelioration of learning and memory impairment.
Discussion
Both plasma Aβ42 (the principle constituent of amyloid plaques found in Alzheimer’s disease) and serum galectin-3 levels were significantly associated with incident mild cognitive impairment in type 2 diabetes patients.
In the preclinical arm of the study, diabetic rats were fed with a high-fat diet together with P-MCP for 4 weeks, along with two control groups: A) just a high-fat diet and B) just P-MCP. Brain galectin-3 levels were measured following the 4 weeks. Galectin-3 levels in both brain and blood were elevated, and cognitive impairment was seen in the diabetic subjects. However, the MCP treated group had significantly lower Gal-3 levels, as well as improved learning and memory, compared to controls.
These findings are significant. Not only do they highlight Gal-3 as a promising therapeutic target in addressing diabetes, metabolic syndrome, and resulting cognitive impairment—they also add to the fast-growing roster of benefits offered by MCP as a multi-targeted adjunct for a wide range of degenerative conditions related to what researchers have called the “culprit biomarker”: Elevated levels of serum Galectin-3.
