The associations of glycosylated hemoglobin with grey matter volume and depression: Investigating mediating role of grey matter volume

Background

Depression has caused enormous health burden to human worldwide. Glycemia has been found as one important risk factor of depression. However, the biological mechanism underlying this relationship remained largely unknown.

Methods

This analysis was derived from a cohort of 33,151 participants in the UK Biobank who provided brain magnetic resonance imaging data from 2014 to 2020. Participants were classified into diabetic, prediabetic and non-diabetic groups, as well as groups aged ≥60 years and <60 years. We assessed the associations between glycosylated hemoglobin (HbA1c), grey matter volume (GMV) in 117 brain regions, and depression based on the multivariable linear and logistic regression. We further investigated the mediation effect of GMV on the relationship between HbA1c and depression.

Results

Higher HbA1c was found to be associated with reduced GMV and depression. Lower GMV was observed associated with depression. Moreover, the association was strongest in prediabetes compared to prediabetic and non-diabetic, and the association was greater in those aged ≥60 years. We further observed a significant mediation effect of GMV on the association between HbA1c and depression, and the proportions of the effect mediated by HbA1c-depression signatured regions was 7.29% (95% CI: 1.43%, 34.38%).

Conclusions

This study suggests that HbA1c is associated with cerebral grey matter abnormality especially in participants aged ≥60 years. In the context of global aging, the unhealthy blood sugar can contribute to more severe brain damage for the population and effective control of blood sugar levels among the elderly can have a positive impact on brain health and potentially reduce the risk of developing depression.