Spatial patterns of structural brain changes in type 2 diabetic patients and their longitudinal progression with intensive control of blood glucose

Abstract

Objective: Understanding the effect of diabetes as well as of alternative treatment strategies on cerebral structure is critical for the development of targeted interventions against accelerated neurodegeneration in type 2 diabetes. We investigated whether diabetes characteristics were associated with spatially specific patterns of brain changes and whether those patterns were affected by intensive versus standard glycemic treatment.

Research design and methods: Using baseline MRIs of 488 participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study, we applied a new voxel-based analysis methodology to identify spatially specific patterns of gray matter and white matter volume loss related to diabetes duration and HbA1c. The longitudinal analysis used 40-month follow-up data to evaluate differences in progression of volume loss between intensive and standard glycemic treatment arms.

Results: Participants with longer diabetes duration had significantly lower gray matter volumes, primarily in certain regions in the frontal and temporal lobes. The longitudinal analysis of treatment effects revealed a heterogeneous pattern of decelerated loss of gray matter volume associated with intensive glycemic treatment. Intensive treatment decelerated volume loss, particularly in regions adjacent to those cross-sectionally associated with diabetes duration. No significant relationship between low versus high baseline HbA1c levels and brain changes was found. Finally, regions in which cognitive change was associated with longitudinal volume loss had only small overlap with regions related to diabetes duration and to treatment effects.

Conclusions: Applying advanced quantitative image pattern analysis methods on longitudinal MRI data of a large sample of patients with type 2 diabetes, we demonstrate that there are spatially specific patterns of brain changes that vary by diabetes characteristics and that the progression of gray matter volume loss is slowed by intensive glycemic treatment, particularly in regions adjacent to areas affected by diabetes.

Figure 1

Three-dimensional surface renderings of ODVBA results. A: GM RAVENS maps in relationship with short vs. long diabetes duration at baseline. Subjects with long diabetes duration (n = 100) had lower RAVENS values (i.e., lower regional GM volume, in the highlighted areas) compared with subjects with short diabetes duration (n = 100). B: GM dRAVENS maps in relationship with standard vs. intensive glycemic treatment arm. Subjects in the intensive treatment arm (n = 221) had lower longitudinal decrease in GM tissue volume in the highlighted areas compared with subjects in the standard treatment arm (n = 267). The green color indicates the detected significant regions with FDR-corrected q < 0.05. The hot color indicates the trends toward significance characterized by the −log (P) values shown in the color bar.

Figure 2

Three-dimensional surface renderings of ODVBA results for longitudinal change in cognitive test scores. Group differences on GM dRAVENS maps between the group with declining cognition (n = 100) vs. nondeclining cognition (n = 100) are shown for DSST (A), RAVLT (B), and STROOP (C) tests. For each three tests, subjects in the group with declining cognition had a higher longitudinal decrease in GM volume in the highlighted areas compared with subjects in the group with nondeclining cognition. The green color indicates the detected significant regions with FDR-corrected q < 0.05. The hot color indicates the trends toward significance characterized by the −log (P) values shown in the color bar.