Structural Gray and White Matter Differences in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Abstract

Context Type 1 Diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycaemia (SH) and impaired awareness of hypoglycaemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI). Objective To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycaemia (NAH). Design General practice, population-based, cross-sectional study. (July 2018 to July 2019) Setting Endocrinology Department, Hospital Santa Creu i Sant Pau. Participants A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration and education level. Main Outcome Measures: Using different neuroimaging techniques, we compared whole-brain grey matter (GM) and white matter (WM) differences. We used voxel-based morphometry (VBM) and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences. Results Compared to patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (p<0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity. Conclusions MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are and cause of a consequence of increased SH episode frequency and increased IAH severity.

Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of Type 1 Diabetes in Children

“…Other studies have also found reductions in GM volume in individuals with T1D, and it has been posited that patients with long-standing T1D may have partial neuronal loss or dysfunction related to their disease. 41,42 Our findings may indicate that cerebral WM is more vulnerable to glycemic injury, and we suspect that a reduction in GM NAA/Cr would also be seen if our participants had long-standing T1D. Alternatively, the absence of effects in GM may simply be related to the small sample size in this pilot study.…”

Gray Matter Brain Alterations in Type 1 Diabetes – Findings Based on Detailed Phenotyping of Neuropathy Status

“…Moreover, it is also suggested that other etiologies may contribute to structural alterations noted in diabetes, which is not directly related to neuropathy status. For instance, several studies have suggested that gray matter regions are vulnerable to hyperglycemia and severe hypoglycemia 30 31 32 . Also, hyperglycemia may result in an accumulation of potentially toxic glucose metabolites, oxidative stress, accelerated formation of advanced glycation end-products, and microvascular changes in the brain 33 .…”

Retinal Microperimetry as a Novel Tool for Early Detection of Cognitive Dysfunction and Brain Damage in Type 1 Diabetes: A Pilot Study

“…Clinical data were collected from hospital records. Cognitive performance by neuropsychological tests, neuroimaging acquisition, and plasma NfL levels, were obtained as per previous studies 7,10,18 . The neuropsychological tests battery included memory alteration test (TAM), the word learning subtest of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) which included CERAD word list memory, recall and recognition; trail making test A and B (TMT-A and TMT-B), phonetic verbal uency, semantic verbal uency, and Boston naming test.…”

“…Using brain magnetic resonance imaging (MRI) we also detected that patients with T1D-IAH had reduced grey matter (GM) volumes and cortical surface areas, especially in frontal and parietal regions, and also showed reduced fractional anisotropy (FA) values in major white matter (WM) tracts, that correlated with both episodes of severe hypoglycemia and IAH severity 10 . Finally, we assessed plasma neuro lament light chain (NfL) levels, a recognized biomarker for neurodegeneration 11 associated to neuronal loss and axonal damage, nding higher levels in patients with T1D-IAH, which correlated to reduced cerebral GM volume and IAH severity 9 .…”