Cognitive impairments are common in patients with type 2 diabetes (T2DM) and adversely impact self-care and glycemic control. However, brain injury in a site that controls cognition (prefrontal cortices; PFC) and its relationship to glycemic outcomes in T2DM remains unclear.

Methods: We examined 9 T2DM patients (age 58.2 ± 4.6 years; BMI 30.3 ± 5.0 kg/m2;3 males) and 47 healthy controls (age 55.7 ± 4.2 years; BMI 26.4 ± 3.0 kg/m2; 29 males) for cognition (Montreal Cognitive Assessment [MoCA]), glycemic control (hemoglobin A1c [A1C]), and PFC status via brain magnetic resonance imaging (MRI). Two high-resolution T1-weighted images were collected using a 3.0-Tesla MRI scanner to evaluate PFC status with voxel-based morphometry (VBM) procedures.

Results: No significant differences in age and gender emerged between T2DM and control subjects. However, BMI values were significantly higher in T2DM subjects over controls. MoCA scores were significantly lower in T2DM patients compared to controls (24.3 ± 2.4 vs. 26.9 ± 2.3; p = 0.004). Mean A1C was 7.6±0.8% (51-68 mmol/mol) in T2DM patients. Reduced PFC volume was observed in T2DM patients compared to controls (left 0.35±0.02 vs. 0.41±0.03, p<0.001; right 0.31±0.02 vs. 0.38±0.02, p<0.001). PFC volume was positively correlated with cognition; left PFC regions (r= 0.94, p=0.002) and right PFC regions (r= 0.89, p=0.007) with age and gender as covariates. Significant negative correlations were found between PFC volume and A1C; left PFC (r= -0.92, p=0.003) and right PFC regions (r=-0.92, p=0.004) with age and gender as covariates.

Conclusions: T2DM patients have PFC brain damage which is associated with cognitive deficits and poor glycemic control. Further research is needed to identify causal relationships between A1C and brain changes in T2DM and to examine interventions to enhance brain/neurogenesis and its impact on A1C.


S.E. Choi: None. B. Roy: None. R. Kumar: None. M. Freeby: None. R.S. Mullur: None. M.A. Woo: None.


National Institutes of Health (R01NR017190)

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