Effects of Alpha-2-HS-glycoprotein on cognitive and emotional assessment in prediabetic and diabetic subjects

Background: High concentrations of Alpha-2-HS-glycoprotein, also called Fetuin-A (Fet-A), are associated with insulin resistance, obesity, non-alcoholic fatty liver disease, type 2 diabetes and polycystic ovary syndrome. Moreover, Fet-A is able to cross the bloodbrain barrier into ischemic brain tissue in adult humans. Although the brain is an important target of insulin action, there is little evidence associating serum levels of Fet-A with psychiatric conditions such as depression and cognitive decline, and no reports about the presence and degree of anxiety disorders. Methods: We have examined cognitive and emotional alterations in a Caucasian population of 94 subjects. Results: Our data confirmed that, irrespective of insulin sensitivity status, circulating Fet-A levels are positively associated with an increased risk of showing signs of depression according to the BDI-II test, and have reported new evidences of a positive association between Fet-A and state- and trait- anxiety, as measured by the STAI questionnaires. In contrast, no association was observed between Fet-A levels and cognitive performance on the MMSE. Limitations: Although the study includes a well-characterized population, the small sample size and cross sectional nature are important limitations, and this results should not be considered definitive. The data are based only on Caucasian subjects and their generalizability to other ethnic groups should be done with caution. Conclusion: Overall, these data suggest for the first time a role of Fet-A as an independent risk factor in the development of symptoms of anxiety and depression in prediabetic and diabetic subjects.