Alterations in white matter volume and integrity in obesity and type 2 diabetes.

Michaela Diamant,Richard G. Ijzerman,Liselotte van Bloemendaal,Jennifer S. ten Kulve,Frederik Barkhof,Dick J. Veltman,Eelco van Duinkerken

doi:10.1007/s11011-016-9792-3

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se.

Highlights

Obesity and type 2 diabetes mellitus (T2DM) are major public health problems, due to their pandemic occurrence, and due to their association with adverse consequences, such as cardiovascular disease, cancer and cerebral complications (Kullmann et al 2015; Geijselaers et al 2015)
5 Department of Psychology, Pontifícia Universidade Católica (PUC-Rio), Rio de Janeiro, RJ, Brazil subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients
In the current study we showed that both white matter integrity, as measured by axial diffusivity, and white matter volume are decreased in obese T2DM patients compared with lean subjects

Summary

Introduction

Obesity and type 2 diabetes mellitus (T2DM) are major public health problems, due to their pandemic occurrence, and due to their association with adverse consequences, such as cardiovascular disease, cancer and cerebral complications (Kullmann et al 2015; Geijselaers et al 2015). T2DM is characterized by hyperglycemia and obesity-related insulin resistance (Kahn 2003; Kahn et al 2006). Patients with T2DM are at an increased risk of (vascular) dementia (Crane et al 2013), stroke (Aoki and Uchino 2011), white matter lesions (Roriz-Filho et al 2009) and cognitive impairment (Benedict et al 2012; Reijmer et al 2010). Obesity is associated with brain disease, including an increased risk of dementia and accelerated cognitive decline at older. Metab Brain Dis (2016) 31:621–629 age, with complementary structural brain changes (Gustafson et al 2003; Gunstad et al 2007; Kullmann et al 2015). Both obesity-related insulin resistance and hyperglycemia seem strong risk factors for cerebral pathology (Rusinek and Convit 2014)

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