Patients with type 2 diabetes mellitus (T2DM) show brain tissue changes in mood and cognitive control sites. However, it is unclear whether brain microstructural tissue changes differ between patients with controlled (hemoglobin A1c [A1C] <7%) and uncontrolled (A1C ≥ 7%) T2DM. Diffusion tensor imaging (DTI) based mean diffusivity (MD) measures water molecular motion within tissue and shows microstructural changes by values reduced in acute and increased in chronic pathological conditions. Methods: We collected DTI and A1C data from 37 T2DM patients (15 controlled; age 56.4±6.8 years, BMI 29.2±6.2 kg/m2, diabetes duration 6.0±4.8 years, A1C 6.2±0.4%, 7 female; 22 uncontrolled; age 57.2±7.4 years, BMI 30.5±5.1 kg/m2, diabetes duration 15.0±9.0 years, A1C 8.2±1.3%, 14 female) and 12 healthy controls (age 54.3±8.2 years, BMI 25.9±4.6 kg/m2, A1C 5.2±0.4%, 5 male) using a 3.0-Tesla magnetic resonance imaging scanner and point-of-care A1C testing. Whole-brain MD maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. healthy controls; uncontrolled T2DM patients vs. healthy controls) using ANCOVA (SPM12; covariates, age and sex; uncorrected threshold, p<0.005).

Results: No significant differences appeared between groups in age or sex. Mean duration of diabetes was significantly different between controlled and uncontrolled T2DM patients (p <0.001). Uncontrolled T2DM patients showed increased MD values in multiple brain areas, including the cingulate, insula, para-hippocampal, hippocampus, cerebellum, basal-forebrain, prefrontal, frontal, and temporal cortices over controlled T2DM patients and healthy controls.

Conclusion: Uncontrolled T2DM patients show widespread chronic brain microstructural changes in areas that are involved in mood and cognition regulation. The findings support tight glycemic control to prevent further brain tissue damages in patients with T2DM.


S.E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott, Novo Nordisk Inc. M.A. Woo: None. R. Kumar: None.


National Institutes of Health (R01NR017190)

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