Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain. This Seminar offers a clinically focused review of the recent developments in type 2 diabetes care including controversies and future directions.Copyright © 2022 Elsevier Ltd. All rights reserved.

Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.

Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM. PubMed, PsycInfo, and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression. A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male, 26,942 control, 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration. T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs).Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and HCs were selected, and their significant peak coordinates (x, y, z) and effect sizes (z-score or t-value) were extracted to perform a voxel-based meta-analysis by anisotropic effect size-signed differential mapping (AES-SDM) 5.15 software.Total 15 studies and 16 datasets (1550 participants) from 7531 results were involved in this study. Compared to HCs, patients with T2DM-CD showed significant and consistent decreased GM in right superior frontal gyrus, medial orbital (PFCventmed. R, BA 11), left superior temporal gyrus (STG. L, BA 48), and right calcarine fissure / surrounding cortex (CAL. R, BA 17), as well as decreased fractional anisotropy (FA) in right inferior network, inferior fronto-occipital fasciculus (IFOF. R), right inferior network, longitudinal fasciculus (ILF. R), and undefined area (32, -60, -42) of cerebellum. Meta-regression showed the positive relationship between decreased GM in PFCventmed.R and MoCA score, the positive relationship between decreased GM in STG.L and BMI, as well as the positive relationship between the decreased FA in IFOF.R and age or BMI.T2DM impairs the cognitive function by affecting the specific brain structures. GM atrophy in PFCventmed. R (BA 11), STG. L (BA 48), and CAL. R (BA 17), as well as WM injury in IFOF. R, ILF. R, and undefined area (32, -60, -42) of cerebellum. And those brain regions may be valuable targets for future researches. Age, BMI, and MoCA score have a potential influence on the altered GM or WM in T2DM-CD.© 2022. The Author(s).

To discuss the relevant studies about the structural and functional changes of the brain in patients with type-2 DM (T2DM) and white matter lesion (WML) in recent years, and to summarize them.T2DM is a common metabolic disease with increasing prevalence worldwide. This disease is closely related to central nervous system and vascular disease, and is considered a risk factor for white matter lesions in the brain. Compared to healthy individuals, WML patients with T2DM exhibit changes in brain perfusion, functional networks, nerve fiber structure, and brain tissue metabolism.We analyzed recent studies related to structural and functional changes in the brain of patients suffering from T2DM and WML and summarized them.Multimodal magnetic resonance imaging (MRI) utilizes noninvasive and sensitive imaging techniques to provide multiparametric information in patients with T2DM to help in clinical practice. It features non-invasively and with high sensitivity assess the histomorphological and functional abnormalities of white matter in patients with T2DM using various parameters. We can use multimodal MRI methods to reflect the microscopic damage of neuromyelin structures and pathological changes of neuronal metabolic functions in WML in T2DM patients, and thus speculate the disease progression. This approach can be helpful for the early diagnosis and treatment of patients with such a disease who do not exhibit neurological deficit, to effectively improve their prognosis.

Type 1 and type 2 diabetes mellitus have an impact on the microstructural environment and cognitive functions of the brain due to its microvascular/macrovascular complications. Conventional Magnetic Resonance Imaging (MRI) techniques can allow detection of brain volume reduction in people with diabetes. However, conventional MRI is insufficiently sensitive to quantify microstructural changes. Diffusion Tensor Imaging (DTI) has been used as a sensitive MRI-based technique for quantifying and assessing brain microstructural abnormalities in patients with diabetes. This systematic review aims to summarise the original research literature using DTI to quantify microstructural alterations in diabetes and the relation of such changes to cognitive status and metabolic profile. A total of thirty-eight published studies that demonstrate the impact of diabetes mellitus on brain microstructure using DTI are included, and these demonstrate that both type 1 diabetes mellitus and type 2 diabetes mellitus may affect cognitive abilities due to the alterations in brain microstructures.

To investigate brain microstructural changes in white matter and gray matter of type 2 diabetes mellitus (T2DM) patients using diffusion kurtosis imaging.Diffusion kurtosis imaging (b values = 0, 1250, and 2500 s/mm) was performed for 30 T2DM patients and 28 controls. FMRIB Software Library with tract-based spatial statistics was used to analyze intergroup differences in fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axial kurtosis (K), and radial kurtosis (K) of multiple white matter regions. Atlas-based ROI analysis was conducted in gray matter structures and some fiber tracts. Correlations between MK changes and clinical measurements were determined.In whole-brain tract-based spatial statistics analysis, T2DM patients exhibited abnormalities in 29.6%, 30.4%, 35.4%, 10.5%, and 26.0% of white matter regions as measured by FA, MD, MK, K, and K, respectively, when compared to the controls. MK reduction was contributed more by the decreased K. In atlas-based analysis, MK detected more ROIs (27/48) with white matter microstructural changes than FA (13/48) and MD (17/48). MK decreased in bilateral thalamus and caudate, while FA showed statistically significant difference only in the left caudate. MK values negatively correlated with disease duration in the genu of corpus callosum and anterior corona radiata (R = -0.512 and -0.459) and positively correlated with neuropsychological scores in the cingulum (hippocampus) (R = 0.466 and 0.440).Diffusion kurtosis imaging detects more brain regions with white matter and gray matter microstructural alterations of T2DM patients than DTI metrics. It provides valuable information for studying the pathology of diabetic encephalopathy and may lead to better imaging biomarkers for monitoring disease progression.• Diffusion kurtosis imaging detects more brain regions with microstructural alterations in white matter and gray matter of T2DM patients than DTI. • Mean kurtosis changes are associated with disease severity and impaired neuropsychological function in T2DM. • Diffusion kurtosis imaging demonstrates potential to assess cognitive impairment in T2DM patients and predict disease progression.

Aims: The study aimed to conduct a meta-analysis to determine the abnormalities of white matter in patients with type 2 diabetes mellitus (T2DM) by identifying the consistency of diffusion tensor imaging (DTI).

Patients with type 2 diabetes mellitus (T2DM) have usually been found cognitive impairment associated with brain white matter (WM) abnormalities. However, findings have varied across studies, and any potential relationship with Alzheimer's disease (AD) remains unclear. The aim of this study was to assess the whole-brain WM integrity of T2DM patients and to compare our findings with those of published AD cases.In this study, we used diffusion tensor imaging (DTI) combined with tract-based spatial statistics (TBSS) to investigate whole-brain WM abnormalities in 48 T2DM patients and 48 healthy controls. The effects of age and gender were also evaluated.In our study, significantly decreasing FA and increasing MD and DA values (P<0.05) were found in some WM regions closely related to the default mode network (DMN), including cingulum, the right frontal lobe involving the right uncinate fasciculus (UF), bilateral parietal lobes involving the superior longitudinal fasciculus (SLF) and the inferior longitudinal fasciculus (ILF), and the right middle temporal gyrus (MTG) involving the UF and the ILF. We also found abnormalities in the thalamus involving the fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR). The damaged regions above are similar to those found in patients with AD, as reported in previous studies.The present study not only provides useful information about the WM regions and tracts affected by T2DM but also offers insight into the underlying neuropathological process in T2DM patients and the relationship between T2DM and AD.

本文旨在利用磁共振成像手段探究尼古丁易感个体的脑结构特征，即脑结构特性对尼古丁依赖程度的预测.选用成年雄性SD大鼠进行纵向研究，利用基于微型渗透压泵的间歇性给药方式对大鼠进行腹腔注射尼古丁14天，随后强制戒断14天.于第0、15、29天进行躯体戒断行为测试以量化其尼古丁依赖严重程度.对第1天的脑结构图像与戒断行为评分进行回归分析，结果发现尼古丁依赖严重程度与双侧前边缘皮层、左侧颗粒状岛叶皮层灰质体积和双侧丘脑白质体积呈负相关，与右侧海马CA1脑区和左侧丘脑灰质体积呈正相关.以上脑区的结构特征，能够作为尼古丁易感的生物标志物，在个体接触尼古丁之前预测其尼古丁依赖风险，对易感人群进行有针对性的早期干预.

1型糖尿病(T1DM)是一种慢性代谢疾病，主要表现为胰岛素分泌量较正常情况下降，会对人体的多个器官和系统造成持续性的损伤．关于糖尿病的横向研究发现糖尿病患者相比于正常人存在着显著的脑萎缩，但关于糖尿病引起的脑萎缩随时间发生进行性改变的研究比较少见．实验采用腹腔注射链脲佐菌素(STZ)来诱导建立大鼠的1型糖尿病模型，运用磁共振成像(MRI)的方法对萎缩的脑区进行定位并在造模后12周和20周两个时间点对脑萎缩的程度进行对比分析，然后运用组织化学染色的方法观察在MRI上出现进行性萎缩的脑区中的神经元所发生的病理改变．MRI的结果表明：STZ诱导的T1DM大鼠相比于正常对照组大鼠出现了显著性的全脑体积、灰质体积和白质体积的萎缩，并且在多个白质脑区和灰质脑区均出现了萎缩程度随着病程的延长而逐渐加重．组织化学染色的结果发现，STZ诱导的T1DM大鼠相对于正常对照组大鼠在体感皮层、运动皮层和海马CA3区，均出现明显的神经元萎缩现象．

Visual deprivation leads to structural neuroplasticity in the blind subjects, including gray matter (GM) and white matter (WM) atrophy and alterations in structural connectivity. The rat model of binocular enucleation (BE) is a frequently used animal model for studying brain plasticity induced by early blindness. Yet few neuroimaging studies have been performed on this model to investigate whether or not the BE rats have image phenotypes similar to or comparable to, those observed in the early blind subjects. The current study aimed to assess brain structural plasticity in BE rats using anatomical magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). The results demonstrated that early BE at postnatal day 4 (P4) caused almost complete degeneration of optic nerve (ON) and optic chiasma (OCH), atrophy in a number of visual and non-visual structures, including optic tract (OT), dorsal lateral geniculate nucleus (DLG) and corpus callosum (CC). The BE rats also exhibited impairments of WM microstructural integrity in the OT, and reduction of structural connectivity between the normal-appearing visual cortex (VC) and somatosensory/motor cortices at 4 months of age, likely as manifestations of deafferentation-induced maldevelopment. The structural neuroplasticity in BE rats observable to structural MRI parallels largely with what has been reported in blind subjects, suggesting that longitudinal neuroimaging studies on animal models of sensory deprivation can provide insights into how the brain changes its wiring and function during development/adaption in response to the lack of sensory stimuli.© 2022 The Authors.

The objective of the present study was to develop a rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g) were divided into two groups and fed with commercially available normal pellet diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58% calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats exhibited significant increase in body weight, basal plasma glucose (PGL), insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared to NPD-fed control rats. Besides, the HFD rats showed significant reduction in glucose disappearance rate (K-value) on intravenous insulin glucose tolerance test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate (K-value) suggested that the feeding of HFD-induced insulin resistance in rats. After 2 weeks of dietary manipulation, a subset of the rats from both groups was injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)). Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection that, however, caused only mild elevation in PGL in NPD-fed rats. Though there was significant reduction in PI level after STZ injection in HFD rats, the reduction observed was only to a level that was comparable with NPD-fed control rats. In addition, the levels of PTG and PTC were further accentuated after STZ treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat-fed/STZ-treated rats simulate natural disease progression and metabolic characteristics typical of individuals at increased risk of developing type 2 diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ-treated rats were found to be sensitive for glucose lowering effects of insulin sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides, the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and PTC) was shown in these diabetic rats. The present study represents that the combination of HFD-fed and low-dose STZ-treated rat serves as an alternative animal model for type 2 diabetes simulating the human syndrome that is also suitable for testing anti-diabetic agents for the treatment of type 2 diabetes.

Type 2 diabetes accounts for 90% of the population with diabetes, and these patients are generally obese and hyperlipidemic. In addition to hyperglycemia, hyperlipidemia is also closely related with diabetic retinopathy. The aim was to investigate retinopathy in a model closely mimicking the normal progression and metabolic features of the population with type 2 diabetes and elucidate the molecular mechanism. Retinopathy was evaluated in rats fed a 45% kcal as fat diet for 8 weeks before administering streptozotocin, 30 mg/kg body weight (T2D), and compared with age- and duration-matched type 1 diabetic rats (T1D) (60 mg/kg streptozotocin). The role of epigenetic modifications in mitochondrial damage was evaluated in retinal microvasculature. T2D rats were obese and severely hyperlipidemic, with impaired glucose and insulin tolerance compared with age-matched T1D rats. While at 4 months of diabetes, T1D rats had no detectable retinopathy, T2D rats had significant retinopathy, their mitochondrial copy numbers were lower, and mtDNA and promoter DNA methylation was exacerbated. At 6 months, retinopathy was comparable in T2D and T1D rats, suggesting that obesity exaggerates hyperglycemia-induced epigenetic modifications, accelerating mitochondrial damage and diabetic retinopathy. Thus, maintenance of good lifestyle and BMI could be beneficial in regulating epigenetic modifications and preventing/retarding retinopathy in patients with diabetes.© 2020 by the American Diabetes Association.

Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function.This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures.T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume.Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.

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.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.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.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.

Type 2 diabetes mellitus (T2DM) patients are highly susceptible to developing dementia, especially for those with mild cognitive impairment (MCI), but its underlying cause is still unclear. In this study, we performed a battery of neuropsychological tests and high-resolution sagittal T1-weighted structural imaging to explore how T2DM affects white matter volume (WMV) and cognition in 30 T2DM-MCI patients, 30 T2DM with normal cognition (T2DM-NC) patients, and 30 age-, sex-, and education-matched healthy control (HC) individuals. The WMV of the whole brain was obtained with automated segmentation methods. Correlations between the WMV of each brain region and neuropsychological tests were analyzed in the T2DM patients. The T2DM-NC patients and HC individuals did not reveal any significant differences in WMV. Compared with the T2DM-NC group, the T2DM-MCI group showed statistically significant reduction in the WMV of seven brain regions, mainly located in the frontotemporal lobe and limbic system, five of which significantly correlated with Montreal Cognitive Assessment (MoCA) scores. Subsequently, we evaluated the discriminative ability of these five regions for MCI in T2DM patients. The WMV of four regions, including left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus had high diagnostic value for MCI detection in T2DM patients (AUC &amp;gt; 0.7). Among these four regions, left precuneus WMV presented the best diagnostic value (AUC: 0.736; sensitivity: 70.00%; specificity: 73.33%; Youden index: 0.4333), but with no significant difference relative to the minimum AUC. In conclusion, T2DM could give rise to the white matter atrophy of several brain regions. Each WMV of left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus could be an independent imaging biomarker to detect cognitive impairment at the early stage in T2DM patients and play an important role in its pathophysiological mechanism.

Incidence of diabetes has increased dramatically. Consequently, diabetes-induced cognitive impairment has attracted increasing attention. This study aimed to explore the changes in brain structure in the diabetic rats with and without cognitive impairment. Morris water maze method was used for screening the diabetic rats with/without cognitive impairment. These diabetic rats and controls were imaged using magnetic resonance imaging that segmented into gray and white matter, which was further analyzed using voxel-based morphology (VBM) and regions of interest (ROI) based image retrieval. The ROI results showed that the whole brain volume decreased in diabetic rats with/without cognitive impairment as compared to the control (P < 0.05). The VBM results showed differences in the caudate putamen and prefrontal cortex in the diabetic rats with/without cognitive impairment. The change in the brain of rats with cognitive impairment occurred primarily in the area associated with cognition, such as caudate putamen and hippocampus, and the bi-directional change occurred in the different area of hippocampus. The current results provided important imaging information for early diagnosis and timely treatment of diabetic cognitive impairment.Copyright © 2018 Elsevier B.V. All rights reserved.

Type 2 diabetes mellitus (T2DM) increases the risk of brain atrophy and dementia. We aimed to elucidate deep grey matter (GM) structural abnormalities and their relationships with T2DM cognitive deficits by combining region of interest (ROI)-based volumetry, voxel-based morphometry (VBM) and shape analysis.We recruited 23 T2DM patients and 24 age-matched healthy controls to undergo T1-weighted structural MRI scanning. Images were analysed using the three aforementioned methods to obtain deep GM structural shapes and volumes. Biochemical and cognitive assessments were made and were correlated with the resulting metrics.Shape analysis revealed that T2DM is associated with focal atrophy in the bilateral caudate head and dorso-medial part of the thalamus. ROI-based volumetry only detected thalamic volume reduction in T2DM when compared to the controls. No significant between-group differences were found by VBM. Furthermore, a worse performance of cognitive processing speed correlated with more severe GM atrophy in the bilateral dorso-medial part of the thalamus. Also, the GM volume in the bilateral dorso-medial part of the thalamus changed negatively with HbA.Shape analysis is sensitive in identifying T2DM deep GM structural abnormalities and their relationships with cognitive impairments, which may greatly assist in clarifying the neural substrate of T2DM cognitive dysfunction.• Type 2 diabetes mellitus is accompanied with brain atrophy and cognitive dysfunction • Deep grey matter structures are essential for multiple cognitive processes • Shape analysis revealed local atrophy in the dorso-medial thalamus and caudatum in patients • Dorso-medial thalamic atrophy correlated to cognitive processing speed slowing and high HbA1c. • Shape analysis has advantages in unraveling neural substrates of diabetic cognitive deficits.

Quantitative T2 magnetic resonance (MR) imaging was used to examine gerbil brains 1, 3, 10, and 30 days after 5 min forebrain ischemia. T2 was increased in the dorsal-lateral striatum 1 and 3 days post-ischemia, and in the hippocampus 3 days post-ischemia. T2 was normal 10 days post-ischemia, and decreased in the hippocampus and dorsal-lateral striatum 30 days post-ischemia. Neuronal counts in the dorsal-lateral striatum and CA1 hippocampal region were uniformly decreased 30 days post-ischemia. The increase in T2 shortly after ischemia is attributed to brain edema localized to regions where neuronal injury developed. The late decrease in T2 may be due to decreased water in gliotic tissue, or to ferritin-positive microglia, following forebrain ischemia. Tissue atrophy at later times gave enlarged ventricles on MR images.

Cerebral small vessel disease is a heterogeneous disease in which various underlying etiologies can lead to different types of white matter hyperintensities (WMH). WMH shape features might aid in distinguishing these different types. In this proof of principle study in patients with type 2 diabetes mellitus (T2DM), we present a novel approach to assess WMH using shape features. Our algorithm determines WMH volume and different WMH shape and location features on 3T MRI scans. These features were compared between patients with T2DM (n = 60) and a matched control group (n = 54). Although a more traditional marker (WMH volume) was not significantly different between groups (natural log transformed Beta (95% CI): 0.07 (-0.11 <-> 0.24)), patients with T2DM showed a larger number of non-punctuate WMH (median (10th-90th percentile), patients: 40 lesions per person (16-86); controls: 26 (5-58)) and a different shape (eccentricity) of punctuate deep WMH (Beta (95% CI): 0.40 (0.23 <-> 0.58)) compared to controls. In conclusion, our algorithm identified WMH features that are not part of traditional WMH assessment, but showed to be distinguishing features between patients with T2DM and controls. Future studies could address these features to further unravel the etiology and functional impact of WMH.

Objective: To study the relationship of Nε-(carboxymethyl)-lysine level (CML) with microstructure changes of white matter (WM), and cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and to discuss the potential mechanism underlying T2DM-associated cognitive impairment. Methods: The study was performed in T2DM patients (n=22) with disease course ≥5 years and age ranging from 65 to 75 years old. A control group consisted of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML levels were measured by enzyme-linked immunosorbent assay, and cognitive function was assessed by Mini-Mental State Examination and Montreal cognitive assessment (MoCA). Results: The total Mini-Mental State Examination score in the patient group (25.72±3.13) was significantly lower than the control group (28.16±2.45) (p&lt;0.05). In addition, the total MoCA score in the patient group (22.15±3.56) was significantly lower than the control group 25.63±4.12) (p&lt;0.01). In the patient group, FA values were significantly decreased in the corpus callosum, cingulate fasciculus, inferior fronto-occipital fasciculus, parietal WM, hippocampus, and temporal lobes relative to corresponding regions of healthy controls (p&lt;0.05). Plasma CML level was negatively correlated with average FA values in the global brain (r=−0.58, p&lt;0.01) and MoCA scores (r=−0.47, p&lt;0.05). Conclusions: In T2DM, WM microstructure changes occur in older patients, and elevations in CML may play a role in the development of cognitive impairment.

Overweight and obesity may significantly worsen glycaemic and metabolic control in type 2 diabetes. However, little is known about the effects of overweight and obesity on the brains of people with type 2 diabetes. Here, we investigate whether the presence of overweight or obesity influences the brain and cognitive functions during early stage type 2 diabetes.This study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in their brain structures and cognition during early stage type 2 diabetes compared with participants with normal weight. Relationships between each of these measures and disease duration were also examined.Global mean cortical thickness was lower in the overweight/obese type 2 diabetes group than in the normal-weight type 2 diabetes group (z = -2.96, p for group effect = 0.003). A negative correlation was observed between disease duration and global mean white matter integrity (z = 2.42, p for interaction = 0.02) in the overweight/obese type 2 diabetes group, but not in the normal-weight type 2 diabetes group. Overweight/obese individuals with type 2 diabetes showed a decrease in psychomotor speed performance related to disease duration (z = -2.12, p for interaction = 0.03), while normal-weight participants did not.The current study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in brain structures and cognition during early stage type 2 diabetes compared with normal-weight participants.

Type 2 diabetes mellitus (T2DM) is often accompanied by cognitive decline and depressive symptoms. Numerous diffusion tensor imaging (DTI) studies revealed microstructural white matter (WM) abnormalities in T2DM but the findings were inconsistent. The present study aimed to conduct a coordinate‐based meta‐analysis (CBMA) to identify statistical consensus of DTI studies in T2DM.

Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior.

\n Xiaoshuan enteric-coated capsule (XSECC) is a drug approved by the Chinese State Food and Drug Administration for the treatment of stroke. This study was to investigate the effects of XSECC on white and gray matter injury in a rat model of ischemic stroke by diffusion tensor imaging (DTI) and histopathological analyses. The ischemia was induced by middle cerebral artery occlusion (MCAO). The cerebral blood flow measured by arterial spin labeling was improved by treatment with XSECC on the 3rd, 7th, 14th and 30th days after MCAO. Spatiotemporal white and gray matter changes in MCAO rats were examined with DTI-derived parameters (fractional anisotropy, FA; apparent diffusion coefficient, ADC; axial diffusivity, λ\n //\n ; radial diffusivity, λ\n ⊥\n ). The increased FA was found in the XSECC treatment group in the corpus callosum, external capsule and internal capsule, linked with the decreased λ\n //\n, λ\n ⊥\n and ADC on the 3rd day and reduced ADC on the 30th day in the external capsule, suggesting XSECC reduced the axon and myelin damage in white matter after stroke. The relative FA in the striatum, cortex and thalamus in XSECC treatment group was significantly increased on the 3rd, 7th, 14th and 30th days accompanied by the increased λ\n //\n on the 3rd day and reduced relative ADC and λ\n ⊥\n on the 30th day, indicating that XSECC attenuated cell swelling and membrane damage in the early stage and tissue liquefaction necrosis in the late stage in gray matter after stroke. Additionally, XSECC-treated rats exhibited increased mean fiber length assessed by diffusion tensor tractography. Moreover, histopathological analyses provided evidence that XSECC relieved nerve cell and myelin damage in white and gray matter after stroke. Our research reveals that XSECC could alleviate white and gray matter injury, especially reducing nerve cell damage and promoting the repair of axon and myelin after ischemic stroke.\n

This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements.

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.