1545-P: Differences in Brain Anatomy between Diabetes Endotypes—Results from the UK-Biobank

Introduction & Objectives: Research suggests that reduced regional brain volumes in specific areas are important for cognitive functions in persons with type 2 diabetes. How this relates to novel diabetes endotypes is unknown.

Methods: We therefore investigated MRI-derived brain volumes from 464 participants of the UK-Biobank, who had up to 5 years of type 2 diabetes duration and available clinical data. We estimated group membership to the diabetes clusters introduced by Ahlqvist et al. using the approach proposed by Antonio-Villa et al. that relies on BMI, HDL, triglycerides, waist, height, age at fMRI and age at diagnosis, sex, glucose, and HbA1c. Differences in brain volumetry between endotypes were tested by ANCOVA adjusting for age with Bonferroni correction for multiple comparisons and post-hoc Tukey tests.

Results: Grey matter volume (p < 0.0001) as well as bilateral volumes of hippocampus (p < 0.01), and ventral striatum (p < 0.0001) showed differences between endotypes. This remained significant even after adjustment for age and correction for multiple testing. Lowest volumes in these brain areas were present in patients of the insulin deficient SIID cluster, who also had significantly lower volumes than healthy controls. Volumes of white matter, thalamus, caudate, putamen, pallidum, and amygdala did not show significant differences between groups.

Conclusion: There are differences in global and subcortical brain volumes between diabetes endotypes even after a short diabetes duration. Most affected areas are important for cognitive functions, suggesting higher risks for cognitive decline especially in the insulin-deficient SIID endotype.<u> </u>