The brain’s default mode network (DMN), having a high rate of basal energy metabolism, is vulnerable to altered glucose metabolism in type 2 diabetes mellitus (T2DM) due to insulin resistance and chronic hyperglycemia. Previous studies showed that functional connectivity and structural connectivity between the DMN nodal regions are compromised in T2DM. In this study, we applied magnetization transfer (MT) imaging to examine, for the first time, the impact of T2DM on the biophysical integrity of the DMN. The results showed that the biophysical integrity of macromolecular protein pools in the posterior cingulate cortex (PCC), a central DMN hub region, was selectively compromised in T2DM, while the other nodal regions of the DMN, including medial prefrontal cortex, lateral inferior parietal cortex, precuneus, and medial and lateral temporal cortices, were biophysically intact when compared with non-diabetic control subjects. Further, the degree of biophysical impairment of the PCC correlated with both hyperglycemia and vascular compromise – the two physiological hallmarks of diabetes. These new findings demonstrate that the PCC is vulnerable in the DMN and may shed light on the molecular neurobiology of T2DM and help elucidate the pathophysiology of diabetes-related cognitive comorbidities and increased risk for dementia.
- Received December 17, 2015.
- Accepted July 25, 2016.
- © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.