Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus

Abstract

Aims/hypothesis: Central nervous system abnormalities, including cognitive and brain impairments, have been documented in adults with type 2 diabetes who also have multiple co-morbid disorders that could contribute to these observations. Assessing adolescents with type 2 diabetes will allow the evaluation of whether diabetes per se may adversely affect brain function and structure years before clinically significant vascular disease develops.

Methods: Eighteen obese adolescents with type 2 diabetes and 18 obese controls without evidence of marked insulin resistance, matched on age, sex, school grade, ethnicity, socioeconomic status, body mass index and waist circumference, completed MRI and neuropsychological evaluations.

Results: Adolescents with type 2 diabetes performed consistently worse in all cognitive domains assessed, with the difference reaching statistical significance for estimated intellectual functioning, verbal memory and psychomotor efficiency. There were statistical trends for executive function, reading and spelling. MRI-based automated brain structural analyses revealed both reduced white matter volume and enlarged cerebrospinal fluid space in the whole brain and the frontal lobe in particular, but there was no obvious grey matter volume reduction. In addition, assessments using diffusion tensor imaging revealed reduced white and grey matter microstructural integrity.

Conclusions/interpretation: This is the first report documenting possible brain abnormalities among obese adolescents with type 2 diabetes relative to obese adolescent controls. These abnormalities are not likely to result from education or socioeconomic bias and may result from a combination of subtle vascular changes, glucose and lipid metabolism abnormalities and subtle differences in adiposity in the absence of clinically significant vascular disease. Future efforts are needed to elucidate the underlying pathophysiological mechanisms.

Fig. 1

MPRAGE image segmentation. Individual MPRAGE images are registered to standard space before segmentation is accomplished. a Normalised MPRAGE image. b Segmented image: grey matter (red), white matter (green) and CSF (white) partitions are overlaid on top of the normalised MPRAGE image

Fig. 2

Sampling of significant FA and ADC clusters. The three rows of images, each showing an orthogonal orientation (axial, coronal, and sagittal), display the clusters with the axes going through the centroid (coordinates in Table 4). (a) WM FA reductions (blue) and (b) GM ADC elevations (yellow/orange) in the type 2 diabetes group