Impairment In Type 2 Diabetes Mellitus Patients Research Articles

Altered cortical thickness-based structural covariance networks in type 2 diabetes mellitus

Cognitive impairment is a common complication of type 2 diabetes mellitus (T2DM), and early cognitive dysfunction may be associated with abnormal changes in the cerebral cortex. This retrospective study aimed to investigate the cortical thickness-based structural topological network changes in T2DM patients without mild cognitive impairment (MCI). Fifty-six T2DM patients and 59 healthy controls underwent neuropsychological assessments and sagittal 3-dimensional T1-weighted structural magnetic resonance imaging. Then, we combined cortical thickness-based assessments with graph theoretical analysis to explore the abnormalities in structural covariance networks in T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. T2DM patients exhibited significantly lower clustering coefficient (C) and local efficiency (Elocal) values and showed nodal property disorders in the occipital cortical, inferior temporal, and inferior frontal regions, the precuneus, and the precentral and insular gyri. Moreover, the structural topological network changes in multiple nodes were correlated with the findings of neuropsychological tests in T2DM patients. Thus, while T2DM patients without MCI showed a relatively normal global network, the local topological organization of the structural network was disordered. Moreover, the impaired ventral visual pathway may be involved in the neural mechanism of visual cognitive impairment in T2DM patients. This study enriched the characteristics of gray matter structure changes in early cognitive dysfunction in T2DM patients.

Gut microbiota regulation of inflammatory cytokines and microRNAs in diabetes-associated cognitive dysfunction.

Type 2 diabetes mellitus (T2DM) has a major comorbidity known as diabetes-associated cognitive dysfunction (DACD). Studies have demonstrated that the gut microbiota is crucial in mediating the cognitive abnormalities that occur in diabetic individuals. Additionally, changes in dietary fatty acid intake levels, inflammatory cytokines, and microRNAs (miRs) have an effect on cognitive performance. However, further studies are needed to identify the link between gut microbiota and cognition in T2DM patients and the role that the above indicators play in this process. In order to provide a new rationale for the treatment of cognitive dysfunction in diabetes, this study was conducted in the middle-aged and elderly Beijing population to examine the differences in gut microbiota between DACD and T2DM patients as well as to further explore the role of erythrocyte membrane fatty acids, inflammatory cytokines, and miRs in gut microbiota-mediated cognitive impairment. According to the results, the abundance of norank_f_Eubacterium_coprostanoligenes_group, Acidaminococcus, Enterorhabdus, and norank_f_Clostridium_methylpentosum_group was higher in DACD patients compared to T2DM patients at the genus level. Compared with T2DM patients, plasma interleukin-12 (IL-12) concentrations were significantly higher in DACD patients than in T2DM patients, and IL-12 was significantly positively correlated with norank_f_Eubacterium_coprostanoligenes_group. In addition, plasma miR-142-5p was significantly positively correlated with Enterorhabdus and norank_f_Eubacterium_coprostanoligenes_group. We therefore hypothesize that cognitive impairment in T2DM patients is associated with altered gut microbial composition and that the effect of microbiota on cognition may be mediated through IL-12 and miR-142-5p. KEY POINTS: • Type 2 diabetes with or without cognitive impairment differs in gut microbiota. • Differential genera of gut microbiota were associated with inflammatory cytokines. • Differential genera of gut microbiota were associated with plasma microRNAs.

Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus

Purpose The purpose of this study was to investigate the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and renal function impairment in type 2 diabetes mellitus (T2DM) patients. Methods PCSK9 levels were measured in T2DM patients, streptozotocin plus high-fat diet (STZ + HFD) mice, human proximal tubular epithelial (HK-2) cells treated with high glucose plus palmitic acid (HGPA) and the corresponding control groups. The T2DM patients were further divided into three groups according to serum PCSK9 levels. An analysis of clinical data was conducted, and a binary logistic regression model was used to test the relationship between potential predictors and urine albumin/urine creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Results PCSK9 levels were higher in the DM group than in the control group in humans, mice and HK-2 cells. The systolic blood pressure (SBP), serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), and urine α1-MG/urine creatinine ratio (UαCR) values in PCSK9 tertile 3 were significantly higher than those in PCSK9 tertile 1 (p < 0.05). The DBP and UACR values were significantly higher in PCSK9 tertile 3 than in PCSK9 tertile 1 and PCSK9 tertile 2 (both p < 0.05). In addition, URCR values were significantly higher in PCSK9 tertile 3 and PCSK9 tertile 2 than in PCSK9 tertile 1 (both p < 0.05). Serum PCSK9 levels were positively correlated with SBP, Scr, BUN, TG, URCR, UαCR and UACR but inversely correlated with eGFR. In STZ + HFD mice, serum PCSK9 levels were positively correlated with Scr, BUN and UACR, which was consistent with the findings in the patients. A logistic regression model revealed that serum PCSK9 is an independent risk factor for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m2. The ROC curve showed that 170.53 ng/mL and 337.26 ng/mL PCSK9 were the best cutoff values for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m2, respectively. Conclusion Serum PCSK9 levels are associated with renal function impairment in T2DM patients and in some patients lower PCSK9 may be helpful to decrease chronic kidney disease.

Association between serum cystatin C and early impairment of cardiac function and structure in type 2 diabetes patients with normal renal function.

Type 2 diabetes mellitus (T2DM) patients may have cardiac remodeling and dysfunction from the early stage of disease. This study aimed to determine the association between cystatin C (CysC) and early cardiac functional or structural impairment in T2DM patients without renal dysfunction. A total of 1135 T2DM patients without renal dysfunction and known heart diseases were included in our study. Cardiac function and structure were evaluated by echocardiography. Patients were diagnosed as left ventricular hypertrophy (LVH), impaired left ventricular (LV) diastolic function, and categorized into four different LV geometry patterns including normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. In multivariate linear regression analyses, CysC was positively associated with interventricular septum, LV mass index, left atrial volume index, E/e' ratio, and negatively associated with Tissue Doppler e', E/A ratio (p < .05). As a continuous variable, increasing CysC levels were associated with prevalence of LVH (OR: 1.47, 95%confidence interval [CI]: 1.22-1.77), impaired LV diastolic function (OR: 1.58, 95%CI: 1.33-1.87), concentric hypertrophy (OR: 1.54, 95%CI: 1.23-1.93) and eccentric hypertrophy (OR: 1.34, 95%CI: 1.00-1.80) according to multivariate logistic regression analyses. While as a categorical variable, the highest CysC quartile (CysC > 1.04 mg/L) was associated with LVH (OR: 2.95, 95%CI: 1.74-5.00), impaired LV diastolic function (OR: 4.09, 95%CI: 2.54-6.60), and concentric hypertrophy (OR: 3.26, 95%CI: 2.05-5.18). CysC was significantly associated with early LV remodeling and cardiac functional impairment in T2DM patients with normal renal function. It could be a reliable and convenient biomarker detecting early impairment of cardiac function and structure in T2DM patients.

Topological Alterations of the Brain Functional Network in Type 2 Diabetes Mellitus Patients With and Without Mild Cognitive Impairment.

The aim of this study was to explore the topological alterations of the brain functional network in type 2 diabetes mellitus (T2DM) patients with and without mild cognitive impairment (MCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory approaches. In total, 27 T2DM patients with MCI, 27 T2DM patients without MCI, and 27 healthy controls (HCs) underwent rs-fMRI scanning. The whole-brain functional network was constructed by thresholding the Pearson’s correlation matrices of 90 brain regions. The topological organization of the constructed networks was analyzed by using graph theory approaches. The global and nodal properties of the participants in the three groups were compared by using one-way ANOVA as well as post hoc Tukey’s t-tests. The relationships between the altered topological properties and clinical features or scores of neuropsychological tests were analyzed in T2DM patients with MCI. At the global level, the global and local efficiency of the patients in the T2DM with MCI group were significantly higher than that of participants in the HCs group, and the length of the characteristic path was significantly lower than that of the participants in the HCs group (p < 0.05). No significant difference was found among the other groups. At the nodal level, when compared with T2DM patients without MCI, T2DM patients with MCI showed significantly increased nodal centrality in four brain regions, which were mainly located in the orbitofrontal lobe and anterior cingulate gyrus (ACG) (p < 0.05). No significant difference was found between the T2DM patients without MCI and HCs. Moreover, nodal degree related coefficient (r = −0381, p = 0.050) and nodal efficiency (r = −0.405, P = 0.036) of the ACG showed a significant closed correlation with the scores of the digit span backward test in the T2DM patients with MCI. Our results suggested that the increased nodal properties in brain regions of the orbitofrontal lobe and ACG were biomarkers of cognitive impairment in T2DM patients and could be used for its early diagnosis. The global topological alterations may be related to the combination of MCI and T2DM, rather than any of them.

Diagnostic Accuracy of Serum Cystatin C for Early Recognition of Nephropathy in Type 2 Diabetes Mellitus.

Objectives Diabetic nephropathy is one of the major complications that develop over time in type 2 diabetes mellitus (T2DM). This prospective study was conducted to assess the diagnostic accuracy of serum cystatin C in detecting diabetic nephropathy at earlier stages. Materials and Methods This study was undertaken on 50 cases of T2DM and 50 healthy subjects as controls. Demographic and anthropometric data and blood and urine samples were collected. The concentration of serum cystatin C (index test) and traditional markers of diabetic nephropathy, serum creatinine, and urinary microalbumin (the reference standard) were estimated. Similarly, blood glucose, glycated haemoglobin (HbA1c), triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and urinary creatine were measured. Results The mean ± SD serum cystatin C was significantly higher in T2DM as compared to control (1.07 ± 0.38 and 0.86 ± 0.12 mg/dl, respectively, p < 0.001). The mean ± SD bodyweight, BMI, W : H ratio, pulse, SBP, and DBP were 66.4 ± 12.6 kg, 26.2 ± 5.6 kg/m2, 1.03 ± 0.09, 78 ± 7, 125 ± 16 mm of Hg, and 77 ± 9 mm of Hg, respectively, in cases. A significant difference in HDL cholesterol (p=0.018) and serum cystatin C (p < 0.001) was observed among different grades of nephropathy. Cystatin C had a significant positive correlation with age (r = 0.323, p=0.022), duration of T2DM (r = 0.326, p=0.021), and UACR (r = 0.528, p < 0.001) and a significant negative correlation with eGFR CKD-EPI cystatin C (r = −0.925, p < 0.001). The area under ROC curve for serum cystatin C (0.611, 95% CI: 0.450–0.772) was greater than for serum creatinine (0.429, 95% CI: 0.265–0.593) though nonsignificant. Conclusion Serum cystatin C concentration increases with the progression of nephropathy and duration of diabetes in Nepalese T2DM patients suggesting cystatin C as a potential marker of renal impairment in T2DM patients.

Association of Vitamin D Level and Nerve Conduction Study Parameters with Cognitive Function in Diabetic Neuropathy Patients

BACKGROUND: Type 2 diabetes mellitus (T2DM) and its major long-term complication, diabetic polyneuropathy (DPN), continue to be a major global health problem and are important contributors of significant disability worldwide. Vitamin D plays a significant role in their pathogenesis as well as in the development of dementia in non-diabetic patients. Nevertheless, the role of Vitamin D in the development of cognitive impairment in DPN patients has not yet been extensively studied. AIM: We aimed to investigate the association between Vitamin D level and cognitive function in DPN patients and to evaluate several potential contributor factors to cognition, including demographic factors, glycemic control, and nerve conduction study (NCS) parameters. METHODS: Thirty-one DPN patients were included in this cross-sectional study. Patients were recruited from the outpatient endocrinology and neurology clinic of Haji Adam Malik General Hospital Medan Indonesia. We used the diabetic neuropathy examination (DNE) scale, diabetic neuropathy symptom (DNS) scale, and NCS to determine the presence and severity of the neuropathy. We measured the levels of Vitamin D, random blood sugar, and glycated hemoglobin (HbA1c). Cognitive function was assessed using the Indonesian version of Montreal Cognitive Assessment (MoCA-INA), trail making test A and B (TMT A and TMT B), and verbal fluency test. RESULTS: Most of the patients were female (80.6%), with a mean age of 55.71 ± 8.34 years. The proportion of patients with abnormal cognitive function was higher than cognitively unimpaired patients. The mean of MoCA-INA score and level of Vitamin D was lower than normal, 23.32 ± 3.00 and 24.91 ± 13.59 ng/ml, respectively. Using the Pearson correlation test, we did not find any significant association of Vitamin D level, NCS parameters, and other clinical characteristics with global cognitive function. Age and level of education were significantly associated with MoCA-INA score. Blood sugar level was significantly higher in patients with normal TMT-A and TMT-B tests compared to patients with abnormal results. CONCLUSION: Vitamin D and NCS parameters are not associated with cognitive function. Of the demographic and clinical characteristics, a significant association exists between age, level of education, and blood sugar level and cognition. This might suggest the complexity underlying cognitive impairment in T2DM patients.

Hippocampal subfields atrophy contribute more to cognitive impairment in middle-aged patients with type 2 diabetes rather than microvascular lesions.

Neurodegeneration and microvascular lesions are related to cognitive impairment in type 2 diabetes mellitus (T2DM). We aimed to use the volume of hippocampal subfields and the burden of white matter hyperintensities (WMH) as neurodegeneration and microangiopathy markers, respectively, to investigate their potential associations with cognitive impairment in T2DM patients. A total of 76 T2DM patients and 45 neurologically unimpaired normal controls were enrolled between February 2016 to August 2018. All participants underwent structural magnetic resonance imaging (MRI) and Montreal Cognitive Assessment (MoCA). The T2DM patients were divided into the T2DM without mild cognitive impairment (T2noMCI) group (n = 44) and the T2DM with mild cognitive impairment (T2MCI) group (n = 32) according to MoCA scores. We used automatic brain segmentation and quantitative technique to assess the volume of twelve hippocampal subfields and WMH on MRI. We used age, sex, education, and total intracranial volume as our covariates and the Bonferroni method for multiple comparison correction. Both the T2MCI group and T2noMCI group showed significant hippocampal subfields atrophy compared to the controls, which were mainly in the left hippocampal tail, left CA1, bilateral molecular layer, bilateral dentate gyrus, and bilateral CA4 (all p < 0.0042). No significant differences in the volume of total WMH, deep-WMH, and periventricular-WMH were found among the three groups. The HbA1c levels were significantly negatively correlated with hippocampal atrophy, and the MoCA scores were positively correlated with bilateral hippocampal volume in T2DM patients and all samples. Mediation analyses demonstrated that the association of HbA1c levels with cognitive function was mediated by hippocampal subfields volume. Widespread hippocampal atrophies across the subfields have been found in middle-aged T2DM patients, which was positively correlated with the MoCA scores and negatively correlated with the HbA1c levels. The association of HbA1c levels with cognitive function was mediated by some crucial hippocampal subfields volume. In middle-aged patients with T2DM, the neurodegeneration is more strongly associated with cognitive impairment than microvascular lesions. Trail Registeration This study was registered on Clinical-Trails.gov (NCT02738671).

Risk Factors for Cognitive Impairment in Patients with Type 2 Diabetes.

Objectives To investigate the risk factors for cognitive impairment in Chinese type 2 diabetes mellitus (T2DM) patients of advanced age and to identify effective biomarkers of mild cognitive impairment (MCI) in these patients. Methods Chinese T2DM patients (n = 120) aged 50–70 years were divided into groups with impaired (mild, moderate, and severe) and normal cognitive function based on Montreal Cognitive Assessment and Mini-Mental State Examination scores. Data regarding demographic characteristics, clinical features of diabetes, biochemical markers, and metabolomics were collected. Results Age, educational level, duration of diabetes, fasting blood glucose (FBG), HbA1c, total cholesterol (TC), triglyceride (TG), and 24-hour urine protein were significantly associated with cognitive impairment in T2DM patients of advanced age. The severity of fundus retinopathy and the incidence of macrovascular disease also differed significantly among the groups (P < 0.05). Metabolomics analysis suggested that increased levels of glutamate (Glu), phenylalanine (Phe), tyrosine (Tyr), proline (Pro), and homocysteine (Hcy) and a decreased level of glutamine (Gln) were significantly associated with cognitive impairment in the T2DM patients (P < 0.05). Receiver operating characteristic curve analysis demonstrated that Glu, Gln, Phe, and Pro levels were significant predictors of cognitive impairment in the T2DM patients. Conclusions Age, educational level, duration of diabetes, and the levels of FBG, HbA1c, TC, TG, and 24-hour urine protein were considered as independent risk factors for cognitive impairment in older T2DM patients. Macrovascular and microvascular diseases also were closely associated with cognitive impairment in these patients. Together, Glu and Gln levels may represent a good predictive biomarker for the early diagnosis of cognitive impairment in T2DM patients.

Association between serum homocysteine level and cognitive function in middle-aged type 2 diabetes mellitus patients.

Type-2 diabetes mellitus (T2DM) is strongly associated with various complications, including cognitive impairment. Diabetic complication is related with structural and functional changes of brain. Studies investigated that homocysteine as an independent risk factor of several organ complications. This marker might have a role in pathogenesis of cognitive impairment in T2DM patients. We aimed to know the association between serum homocysteine level and cognitive impairment in middle-aged T2DM populations. The study was a cross-sectional study involving 97 T2DM patients aged <60 years old. Cognitive assessment was based on validated Indonesian version of Montreal Cognitive Assessment (MoCA-INA) test. Besides, serum homocysteine level (Hcy) was measured based on standard laboratory assay. Filling out the questionnaire of MoCA-INA was conducted when patients came to take the blood sample. This study used independent t-test, chi-square and multivariate logistic regression model to analyze the data. There were 47 subjects (48.5%) with mild cognitive impairment (MCI). Delayed recall was the most impaired domain (94.8%). There was no significant mean difference of serum Hcy level in MCI and non-MCI group (11.99±3.27 μmol/L vs 12.36±4.07 μmol/L respectively, p = 0.62). Final model of logistic regression showed no association between serum Hcy and cognitive function after adjusting confounding variables (OR: 1.778; 95%CI: 0.69–4.54). Further investigation involving slight elderly T2DM patients with larger sample size should be conducted to confirm this finding.

In Addition to Poor Glycemic Control, a High Level of Irisin in the Plasma Portends Early Cognitive Deficits Clinically in Chinese Patients With Type 2 Diabetes Mellitus.

Background and Objectives: Irisin plays an important role in the metabolism and homeostasis of energy balance, which is involved in cognitive impairment. This study aimed to investigate the role of irisin in mild cognitive impairment (MCI) among Chinese patients with type 2 diabetes mellitus (T2DM).Methods: We recruited 133 Chinese patients with T2DM, and divided them according to the Montreal Cognitive Assessment score. Demographic data were collected and the level of irisin in the plasma was determined. In addition, the results of neuropsychological testing were examined. The concentration of irisin in the plasma was measured using an enzyme immunoassay.Results: A total of 59 patients were diagnosed with MCI and 74 patients were included as healthy-cognition controls. The level of irisin in the plasma (p = 0.043) and homeostasis model of assessment for insulin resistance (p = 0.032) in diabetic patients with MCI were higher than those observed in the healthy controls. A higher level of irisin in the plasma was associated with impaired overall cognition, specifically executive function. Linear regression analysis suggested that irisin (p = 0.017) and glycosylated hemoglobin (p = 0.036) were independent factors of diabetic MCI.Conclusions: The level of irisin in the plasma correlated with cognitive impairment in T2DM patients, particularly with executive function. These results further suggest that, in addition to poor glycemic control, a high level of irisin in the plasma portends early cognitive deficits clinically in Chinese patients with T2DM.

Attenuated serum 25-hydroxyvitamin D and vitamin D binding protein associated with cognitive impairment in patients with type 2 diabetes.

PurposeClinical studies suggest that 25-hydroxyvitamin D (25[OH]D) deficiency plays a pivotal role in both type 2 diabetes mellitus (T2DM) and cognitive impairment. However, it is unclear if 25(OH)D deficiency could be a possible cause of cognitive impairment in T2DM. Vitamin-D binding protein (VDBP) acts as a major 25(OH)D transporter. Preclinical study has demonstrated improvement in cognitive function by VDBP via inhibiting synaptic degeneration. The aim of the study was to assess the association between serum 25(OH)D, VDBP and cognitive impairment in T2DM patients.Patients and methodsIn this case-control study, cognitive function was assessed using the Mini-Mental State Examination (MMSE) and serum 25(OH)D and VDBP levels were estimated using ELISA kits.ResultsA total of 88 subjects were included in the study. T2DM patients had lower serum 25(OH)D (p=0.02), VDBP levels (p=0.04) and MMSE scores (p<0.0001) than controls. T2DM patients had higher prevalence of 25(OH)D deficiency and insufficiency, aOR 0.322 (0.128–0.809), p=0.016 and cognitive impairment, aOR 4.405 (1.617–12.002); p=0.004. Cognitive impairment was associated with serum 25(OH)D, aOR 0.131 (0.027–0.638); p=0.014 and VDBP, aOR 1.008 (1.001–1.015), p=0.029. A general linear model showed a significant association of MMSE with serum 25(OH)D (p=0.022).ConclusionSerum 25(OH)D deficiency and cognitive impairment was higher in T2DM patients. Routine assessment of cognitive function is suggested to prevent further behavioral complications. The association of VDBP and cognitive impairment in T2DM needs further exploration.

White Matter Microstructural Change Contributes to Worse Cognitive Function in Patients With Type 2 Diabetes.

Patients with type 2 diabetes mellitus (T2DM) have a considerably high risk of developing dementia, especially for those with mild cognitive impairment (MCI). The investigation of the microstructural change of white matter (WM) between T2DM with amnesic MCI (T2DM-aMCI) and T2DM with normal cognition (T2DM-NC) and their relationships to cognitive performances can help to understand the brain variations in T2DM-related amnesic cognitive impairment. In the current study, 36 T2DM-aMCI patients, 40 T2DM-NC patients, and 40 healthy control (HC) individuals underwent diffusion tensor image and T1-weighted MRI scans and comprehensive cognition assessments. All of these cognitive functions exhibited intergroup ranking differences in patients. The T2DM-NC patients and HC individuals did not reveal any significant differences in WM integrity. The T2DM-aMCI patients showed disrupted integrity in multiple WM tracts compared with HC and T2DM-NC. Specifically, the damaged WM integrity of the right inferior fronto-occipital fasciculus and the right inferior longitudinal fasciculus exhibited significant correlations with episodic memory and attention function impairment in T2DM patients. Furthermore, cognitive impairment-related WM microstructural damage was associated with the degeneration of cortex connected to the affected WM tract. These findings indicate that degeneration exists extensively in WM tracts in T2DM-aMCI, whereas no brain WM damage is evident in T2DM-NC.

Brain microstructural alterations in type 2 diabetes: diffusion kurtosis imaging provides added value to diffusion tensor imaging.

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 2500s/mm2) 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.

Altered Brain Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Patients: A Resting-State fMRI Study.

Type 2 diabetes mellitus (T2DM) affects a vast population and is closely associated with cognitive impairment. However, the mechanisms of cognitive impairment in T2DM patients have not been unraveled. Research on the basic units (nodes or hubs and edges) of the brain functional network on the basis of neuroimaging may advance our understanding of the network change pattern in T2DM patients. This study investigated the change patterns of brain functional hubs using degree centrality (DC) analysis and the connectivity among these hubs using functional connectivity and Granger causality analysis. Compared to healthy controls, the DC values were higher in the left anterior cingulate gyrus (ACG) and lower in the bilateral lateral occipital cortices (LOC) and right precentral gyrus (PreCG) in T2DM patients. The functional connectivity between the left ACG and the right PreCG was stronger in T2DM patients, whereas the functional connectivity among the right PreCG and bilateral LOC was weaker. A negative causal effect from the left ACG to left LOC and a positive effect from the left ACG to right LOC were observed in T2DM patients, while in healthy controls, the opposite occurred. Additionally, the reserve of normal brain function in T2DM patients was negatively associated with the elevated glycemic parameters. This study demonstrates that there are brain functional hubs and connectivity alterations that may reflect the aberrant information communication in the brain of T2DM patients. The findings may advance our understanding of the mechanisms of T2DM-related cognitive impairment.

Effects of Regular Physical Activity on the Cognitive Performance of Type 2 Diabetic Patients: A Systematic Review.

Cognitive decline has been shown to be associated with long-term type 2 diabetes mellitus (T2DM). This review analyzes the present literature to ascertain the role of regular physical activity (PA) for the functioning of the diabetic brain. PubMed was systematically searched for relevant publications up to July 2017. Four cross-sectional, one longitudinal observational, and nine interventional studies with a total of ∼7000 T2DM subjects are included in this review. Some significant positive relationships between the PA level of T2DM patients and their performance in several cognitive tests are reported in the cross-sectional studies. The longitudinal observational study implies a higher risk for developing dementia/mild cognitive impairment in T2DM patients with low PA behavior. Some significantly improved cognitive test results are reported for T2DM patients following physical training (PT) in six interventional studies. The quality of most of the training studies is low due to small sample sizes and/or missing control groups. PT may potentially contribute to improving the cognitive performance in T2DM patients. Additional high-quality studies with standardized cognitive assessments are needed to further determine the dose-effect relationships between PA and cognitive performance in T2DM patients.

Reduced Gray Matter Volume in Patients with Type 2 Diabetes Mellitus.

Background and Purpose: Previous studies of voxel-based morphometry (VBM) have found that patients with type 2 diabetes mellitus (T2DM) exhibit gray matter alterations, but these findings are inconsistent and have not been quantitatively reviewed. Therefore, the aim of this study was to conduct a quantitative meta-analysis of VBM studies of patients with T2DM.Materials and Methods: The seed-based d mapping method was applied to quantitatively estimate the regional gray matter abnormalities in T2DM patients. We also used meta-regression to explore the effects of some demographics and clinical characteristics.Results: Seven studies, with 8 datasets comprising 530 participants with T2DM and 549 non-T2DM controls, were included. The pooled and subgroup meta-analyses found that T2DM patients showed robustly reduced gray matter in the bilateral superior temporal gyrus, middle temporal gyrus, medial superior frontal gyrus, insula, median cingulate cortex, precuneus cortex and the left lentiform nucleus extending into the parahippocampus. The meta-regression also found that the percentage of female patients with T2DM was negatively associated with gray matter in the right superior temporal gyrus and illness duration was negatively associated with gray matter in the right middle temporal gyrus.Conclusion: This meta-analysis indicates that T2DM patients have significantly and robustly reduced gray matter mainly in the cortical-striatal-limbic networks, which are associated with human cognition. Thereby implicating this finding in the pathophysiology of cognitive impairment in T2DM patients.

Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case–Control Study

BackgroundBoth type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3β (GSK-3β) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients. MethodsThe cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3β activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses. FindingsWe recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3β and pS9GSK3β between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ε4 allele, higher olfactory score and higher rGSK-3β (ratio of total GSK-3β to Ser9-phosphorylated GSK-3β) in the training set and the validation set. The OR values of age, ApoE ε4 gene, olfactory score and rGSK-3β were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ε4 gene, olfactory score and rGSK-3β were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively. InterpretationAging, activation of peripheral circulating GSK-3β, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy.

Family Functioning in Chinese Type 2 Diabetic Patients with and without Depressive Symptoms: A Cross-Sectional Study

Background: Patients with depression or type 2 diabetes mellitus (T2DM) often have associated impaired family functioning. The purpose of this study was: (1) to explore the family functioning of T2DM patients with and without depressive symptoms and (2) to explore the relationship between depressive symptoms and family impairment in T2DM patients with depressive symptoms. This study used a cross-sectional design. Sampling and Methods: A sample of 32 patients with T2DM who had depressive symptoms and 229 patients with T2DM who did not have depressive symptoms completed the Chinese versions of the Family Assessment Device (FAD) and the Beck Depression Inventory. Results: This study showed that there were differences in duration of diabetes and some FAD dimensions between T2DM patients with and without depressive symptoms (p < 0.01). There were also differences in the frequencies of FAD dimensions between T2DM patients with and without depressive symptoms (p < 0.01). Age, duration of diabetes and family function were predicting factors of depressive symptoms among T2DM patients (p < 0.01). Conclusions: The T2DM patients with depressive symptoms had more unhealthy FAD dimensions than the T2DM patients without depressive symptoms. The family functioning of T2DM patients with depressive symptoms was worse than that of T2DM patients without depressive symptoms. Age, duration of diabetes and some dimensions of FAD were associated with depressive symptoms in the T2DM patients.