Reduced White Matter Microstructural Integrity in Prediabetes and Diabetes: A Population-based Study

Background: White matter (WM) microstructural abnormalities have been observed in diabetes. However, evidence of prediabetes is currently lacking. This study aims to investigate the WM integrity in prediabetes and diabetes. We also assess the association of WM abnormalities with glucose metabolism status and continuous glucose measures.

Methods: The WM integrity was analyzed using cross-sectional baseline data from a population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study. The cohort, including a total of 2218 cases with the mean age of 61.3 ± 6.6 years and 54.1% female, consisted of 1205 prediabetes which are categorized into two subgroups (a group of 254 prediabetes with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and the other group of 951 prediabetes without combined IFG/IGT), 504 diabetes, and 509 normal control subjects. Alterations of WM integrity were determined by diffusion tensor imaging along with tract-based spatial statistics analysis to compare diffusion metrics on WM skeletons between groups. The mixed-effects multivariate linear regression models were used to assess the association between WM microstructural alterations and glucose status.

Findings: Microstructural abnormalities distributed in local WM tracts in prediabetes with combined IFG/IGT and spread widely in diabetes. These WM abnormalities are associated with higher glucose measures.

Interpretation: Our findings suggest that WM microstructural abnormalities are already present at the prediabetes with combined IFG/IGT stage. Preventative strategies should begin early to maintain normal glucose metabolism and avert further destruction of WM integrity.

Funding: Partially supported by National Key R&D Program of China (2016YFC0901002).