Cortical and subcortical gray matter structural alterations in normoglycemic obese and type 2 diabetes patients: relationship with adiposity, glucose, and insulin

Gabriel Bernardes,Eelco Van Duinkerken,Eelco Van Duinkerken,Eelco Van Duinkerken,Richard G Ijzerman,Jesus Landeira-Fernandez,Michaela Diamant,Jennifer S Ten Kulve,Dick J Veltman,Liselotte Van Bloemendaal,Frederik Barkhof,Frederik Barkhof

doi:10.1007/s11011-018-0223-5

Abstract

Type 2 diabetes (T2DM) is associated with structural cortical and subcortical alterations, although it is insufficiently clear if these alterations are driven by obesity or by diabetes and its associated complications. We used FreeSurfer5.3 and FSL-FIRST to determine cortical thickness, volume and surface area, and subcortical gray matter volume in a group of 16 normoglycemic obese subjects and 28 obese T2DM patients without clinically manifest micro- and marcoangiopathy, and compared them to 31 lean normoglycemic controls. Forward regression analysis was used to determine demographic and clinical correlates of altered (sub)cortical structure. Exploratively, vertex-wise correlations between cortical structure and fasting glucose and insulin were calculated. Compared with controls, obese T2DM patients showed lower right insula thickness and lower left lateral occipital surface area (PFWE < 0.05). Normoglycemic obese versus controls had lower thickness (PFWE < 0.05) in the right insula and inferior frontal gyrus, and higher amygdala and thalamus volume. Thalamus volume and left paracentral surface area were also higher in this group compared with obese T2DM patients. Age, sex, BMI, fasting glucose, and cholesterol were related to these (sub)cortical alterations in the whole group (all P < 0.05). Insulin were related to temporal and frontal structural deficits (all PFWE < 0.05). Parietal/occipital structural deficits may constitute early T2DM-related cerebral alterations, whereas in normoglycemic obese subjects, regions involved in emotion, appetite, satiety regulation, and inhibition were affected. Central adiposity and elevated fasting glucose may constitute risk factors.

Highlights

Type 2 diabetes (T2DM) is associated with structural cortical and subcortical alterations, it is insufficiently clear if these alterations are driven by obesity or by diabetes and its associated complications
Thickness was lower in these regions and the pars opercularis in the normoglycemic obese participants compared with the controls (PFWE = 0.019; Fig. 1; Table 3)
There were no differences between the normoglycemic obese and obese Type 2 diabetes mellitus (T2DM) groups (PFWE > 0.05), and the conjunction analysis showed a trend toward statistical significance for a cluster comprising the insula, extending into the transverse and superior temporal and supramarginal regions (PFWE = 0.073)

Summary

Introduction

Type 2 diabetes (T2DM) is associated with structural cortical and subcortical alterations, it is insufficiently clear if these alterations are driven by obesity or by diabetes and its associated complications. Type 2 diabetes mellitus (T2DM) and obesity are both worldwide health concerns, which are related to an increased risk of cardio- and cerebrovascular disease, cancer, cognitive impairment, and dementia (Reijmer et al 2010; McCrimmon et al 2012; Karlin et al 2012) Cerebral damage, such as loss of (sub)cortical gray and white matter volume, and changes in brain functioning are frequently observed in obese and T2DM groups (Widya et al 2011; McCrimmon et al 2012; Moran et al 2013; Moulton et al 2015). Risk factors identified so far include BMI, hypertension, increased glucose levels, insulin resistance and cholesterol (Kullmann et al 2016; Wennberg et al 2016)

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