Prediction of microvascular complications in diabetic patients without obstructive coronary stenosis based on peri-coronary adipose tissue attenuation model.

OBJECTIVES: To investigate the predictive value of peri-coronary adipose tissue (PCAT) attenuation for microvascular complications in diabetic patients without significant stenosis and to develop a prediction model for early risk stratification. METHODS: This study retrospectively included patients clinically identified for coronary computed tomography angiography (CCTA) and type 2 diabetes between January 2017 and December 2020. All patients were followed up for at least 1 year. The clinical data and CCTA-based imaging characteristics (including PCAT of major epicardial vessels, high-risk plaque features) were recorded. In the training cohort comprising of 579 patients, two models were developed: model 1 with the inclusion of clinical factors and model 2 incorporating clinical factors + RCAPCAT using multivariable logistic regression analysis. An internal validation cohort comprising 249 patients and an independent external validation cohort of 269 patients were used to validate the proposed models. RESULTS: Microvascular complications occurred in 69.1% (758/1097) of the current cohort during follow-up. In the training cohort, model 2 exhibited improved predictive power over model 1 based on clinical factors (AUC = 0.820 versus 0.781, p = 0.003) with lower prediction error (Brier score = 0.146 versus 0.164) compared to model 1. Model 2 accurately categorized 78.58% of patients with diabetic microvascular complications. Similar performance of model 2 in the internal validation cohort and the external validation cohort was further confirmed. CONCLUSIONS: The model incorporating clinical factors and RCAPCAT predicts the development of microvascular complications in diabetic patients without significant coronary stenosis. KEY POINTS: • Hypertension, HbA1c, duration of diabetes, and RCAPCAT were independent risk factors for microvascular complications. • The prediction model integrating RCAPCAT exhibited improved predictive power over the model only based on clinical factors (AUC = 0.820 versus 0.781, p = 0.003) and showed lower prediction error (Brier score=0.146 versus 0.164).

18F-Sodium Fluoride Positron Emission Tomography Activity Predicts the Development of New Coronary Artery Calcifications.

OBJECTIVE: The coronary calcium score (CCS) predicts cardiovascular disease risk in individuals with diabetes, and rate of progression of CCS is an additional and incremental marker of risk. 18F-sodium fluoride positron emission tomography (18F-NaF PET) detects early and active calcifications within the vasculature. We aimed to ascertain the relationship between 18F-NaF PET activity and CCS progression in patients with diabetes. Approach and Results: We identified individuals between 50 and 80 years with diabetes and no history of clinical coronary artery disease. Those with a CCS ≥10 were invited to undergo 18F-NaF PET scanning and then repeat CCS >2 years later. 18F-NaF PET and CCS analysis were performed on a per-coronary and a per-patient level. We compared the proportion of CCS progressors in 18F-NaF PET-positive versus 18F-NaF PET-negative coronary arteries. Forty-one participants with 163 coronary arteries underwent follow-up CCS 2.8±0.5 years later. 18F-NaF PET-positive coronary arteries (n=52) were more likely to be CCS progressors, compared with negative coronary arteries (n=111; 86.5% versus 52.3%, P<0.001). Adjusting for baseline CCS, 18F-NaF PET-positive disease was an independent predictor of subsequent CCS progression (odds ratio, 2.92 [95% CI, 1.32-6.45], P=0.008). All subjects (100%, 15/15) with ≥2 18F-NaF-positive coronary arteries progressed in CCS. CONCLUSIONS: In subjects with diabetes, 18F-NaF PET positivity at baseline, independently predicted the progression of calcifications within the coronary arteries 2.8 years later. These findings suggest 18F-NaF PET may be a promising technique for earlier identification of patients at higher risk of cardiovascular events.

Circulating biomarkers, echocardiographic parameters, and incident subclinical atrial fibrillation in patients with diabetes and hypertension.

BACKGROUND: Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at high risk of AF and stroke. Biomarkers and echocardiographic parameters could, however, help identify patients benefitting most from LTRM. The aim of this study was to investigate, whether circulating biomarkers of cardiac and vascular function (brain natriuretic peptide (BNP), cardiac troponin I (cTnI), copeptin, and mid-regional proadrenomedullin (MR-proADM)) and echocardiographic parameters were associated with incident subclinical AF (SCAF) in a population at high risk of stroke in the presence of AF. For this purpose, we investigated individuals ≥65 years of age with hypertension and diabetes mellitus, but no history or symptoms of AF or other cardiovascular disease (CVD). METHODS: We included 82 consecutive patients (median age 71.3 years (IQR 67.4-75.1)). All patients received an insertable cardiac monitor (ICM) and were followed for a median of 588 days (IQR 453-712). On the day of ICM implantation, a comprehensive echocardiogram and blood samples were obtained. RESULTS: During a median follow-up of 588 days (IQR: 453-712 days), incident SCAF occurred in 17 patients (20.7%) with a median time to first-detected episode of 91 days (IQR 41-251 days). MR-proADM (median 0.87 nmol/L (IQR 0.76-1.02) vs 0.78 nmol/L (IQR 0.68-0.98)) and copeptin (median 13 pmol/L (IQR 9-17) vs 8 pmol/L (IQR 4-18)) levels were insignificantly higher in patients with incident SCAF. BNP and cTnI concentrations and echocardiographic parameters were similar in the two groups. CONCLUSIONS: MR-proADM, BNP, cTnI, copeptin, and several echocardiographic parameters were not associated with incident SCAF in this cohort of patients with hypertension and diabetes, but without any underlying CVD.

Classification of type 2 diabetes mellitus with or without cognitive impairment from healthy controls using high-order functional connectivity.

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and may progress to dementia. However, the brain functional mechanism of T2DM-related dementia is still less understood. Recent resting-state functional magnetic resonance imaging functional connectivity (FC) studies have proved its potential value in the study of T2DM with cognitive impairment (T2DM-CI). However, they mainly used a mass-univariate statistical analysis that was not suitable to reveal the altered FC "pattern" in T2DM-CI, due to lower sensitivity. In this study, we proposed to use high-order FC to reveal the abnormal connectomics pattern in T2DM-CI with a multivariate, machine learning-based strategy. We also investigated whether such patterns were different between T2DM-CI and T2DM without cognitive impairment (T2DM-noCI) to better understand T2DM-induced cognitive impairment, on 23 T2DM-CI and 27 T2DM-noCI patients, as well as 50 healthy controls (HCs). We first built the large-scale high-order brain networks based on temporal synchronization of the dynamic FC time series among multiple brain region pairs and then used this information to classify the T2DM-CI (as well as T2DM-noCI) from the matched HC based on support vector machine. Our model achieved an accuracy of 79.17% in T2DM-CI versus HC differentiation, but only 59.62% in T2DM-noCI versus HC classification. We found abnormal high-order FC patterns in T2DM-CI compared to HC, which was different from that in T2DM-noCI. Our study indicates that there could be widespread connectivity alterations underlying the T2DM-induced cognitive impairment. The results help to better understand the changes in the central neural system due to T2DM.

Network Efficiency Mediates the Relationship Between Vascular Burden and Cognitive Impairment: A Diffusion Tensor Imaging Study in UK Biobank.

Background and Purpose- Cerebrovascular disease contributes to age-related cognitive decline, but the mechanisms underlying this phenomenon remain incompletely understood. We hypothesized that vascular risk factors would lead to cognitive impairment through the disruption of brain white matter network efficiency. Methods- Participants were 19 346 neurologically healthy individuals from UK Biobank that underwent diffusion MRI and cognitive testing (mean age=62.6). Global efficiency, a measure of network integration, was calculated from white matter networks constructed using deterministic diffusion tractography. First, we determined whether demographics (age, sex, ethnicity, socioeconomic status, and education), vascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, smoking, body mass index), and white matter hyperintensities were related to global efficiency using multivariate linear regression. Next, we used structural equation modeling to model a multiple regression. The dependent variable was a latent cognition variable using all cognitive data, while independent variables were a latent factor including all vascular risk factors (vascular burden), demographic variables, white matter hyperintensities, and global efficiency. Finally, we used mediation analysis to determine whether global efficiency explained the relationship between vascular burden and cognition. Results- Hypertension and diabetes mellitus were consistently associated with reduced global efficiency even after controlling for white matter hyperintensities. Structural equation models revealed that vascular burden was associated with cognition (P=0.023), but not after adding global efficiency to the model (P=0.09), suggesting a mediation effect. Mediation analysis revealed a significant indirect effect of global efficiency on cognition through vascular burden (P<0.001), suggesting a partial mediation effect. Conclusions- Vascular burden is associated with reduced global efficiency and cognitive impairment in the general population. Network efficiency partially mediates the relationship between vascular burden and cognition. This suggests that treating specific risk factors may prevent reductions in brain network efficiency and preserve cognitive functioning in the aging population.

Neuropathologic and Cognitive Correlates of Enlarged Perivascular Spaces in a Community-Based Cohort of Older Adults.

BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function, and vascular dementia. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, the purpose of this study was to assess the neuropathologic correlates of EPVS in a large community-based cohort of older adults. The cognitive correlates of EPVS over and beyond those of other pathologies were also assessed. METHODS: This study included 654 older deceased and autopsied participants of 3 longitudinal community-based studies of aging that had available data on cognition, ex vivo brain magnetic resonance imaging, and detailed neuropathologic examination. EPVS seen on ex vivo magnetic resonance imaging were histologically validated. Experienced observers rated EPVS burden in ex vivo magnetic resonance imaging using a semiquantitative 4-level scale. Elastic-net regularized ordinal logistic regression was used to investigate associations of EPVS burden with age-related neuropathologies. Mixed-effects models of cognition controlling for neuropathologies, demographics, and clinical factors, were used to determine whether EPVS burden has additional contributions to cognitive decline. RESULTS: EPVS burden in the whole group was associated with gross infarcts (odds ratio=1.67, P=0.0017) and diabetes mellitus (odds ratio=1.73, P=0.004). When considering only nondemented participants (with mild or no cognitive impairment), EPVS burden was associated with gross infarcts (odds ratio=1.74, P=0.016) and microscopic infarcts (odds ratio=1.79, P=0.013). EPVS burden was associated with faster decline in visuospatial abilities (estimate=-0.009, P=0.028), in the whole group, as well as lower levels of semantic memory (estimate=-0.13, P=0.048) and visuospatial abilities (estimate=-0.11, P=0.016) at the time of death. CONCLUSIONS: EPVS and infarcts may share similar neurobiological pathways regardless of dementia status. EPVS burden is linked to diabetes mellitus independently of neuropathologies, extending recent findings in animal studies implicating diabetes mellitus in impairment of the glymphatic system. Finally, EPVS burden may reflect additional brain tissue injury that may contribute to cognitive decline, not captured with traditional neuropathologic measures.

Brain microstructural abnormalities in type 2 diabetes mellitus: A systematic review of diffusion tensor imaging studies.

Type 2 diabetes mellitus (T2DM) is associated with deficits in the structure and function of the brain. Diffusion tensor imaging (DTI) is a highly sensitive method for characterizing cerebral tissue microstructure. Using PRISMA guidelines, we identified 29 studies which have demonstrated widespread brain microstructural impairment and topological network disorganization in patients with T2DM. Most consistently reported structures with microstructural abnormalities were frontal, temporal, and parietal lobes in the lobar cluster; corpus callosum, cingulum, uncinate fasciculus, corona radiata, and internal and external capsules in the white matter cluster; thalamus in the subcortical cluster; and cerebellum. Microstructural abnormalities were correlated with pathological derangements in the endocrine profile as well as deficits in cognitive performance in the domains of memory, information-processing speed, executive function, and attention. Altogether, the findings suggest that the detrimental effects of T2DM on cognitive functions might be due to microstructural disruptions in the central neural structures.

18F-Sodium Fluoride Imaging of Coronary Atherosclerosis in Ambulatory Patients With Diabetes Mellitus.

Objective- Although patients with diabetes mellitus (DM) are considered at high risk of cardiovascular events, there is growing evidence that this notion is incorrect. Atherosclerosis imaging may identify patients at risk. Approach and Results- We performed coronary atherosclerosis with 18F-sodium fluoride (NaF) positron emission tomography/computed tomography and gated chest computed tomography for coronary artery calcium in 88 consecutive ambulatory patients with DM on a stable medical regimen. NaF has been shown to localize avidly in culprit lesions of patients with acute coronary syndromes and may identify unstable plaques. NaF activity was measured as target (coronary arteries)-to-background (left ventricular pool) ratio (TBR). High TBR was defined as ≥1.5. The mean age of the cohort was 54±14 years, 55% had type 2 DM, 65% were men, the median HgbA1c (hemoglobin A1c) and LDL (low-density lipoprotein) cholesterol were 7.5% (interquartile range, 7.1-8.5) and 1.9 mmol/L (interquartile range, 1.5-2.6), respectively. Mean coronary artery calcium score was 374±773, and median TBR was 1.2. Coronary artery TBR ≥1.5 was detected in 13 (15%) patients. In univariable analyses, male sex ( P=0.0002), estimated glomerular filtration rate ( P=0.02), and total coronary artery calcium score ( P=0.04) were associated with TBR. In multivariable analyses, TBR >median was associated with male sex ( P=0.0001) and statin use ( P=0.042). Conclusions- In ambulatory patients with DM asymptomatic for cardiovascular disease, the prevalence of potentially vulnerable plaques detected with NaF was low, but in the absence of follow-up data at this stage, we cannot assess the import of this information. Future research will establish whether NaF imaging helps risk stratify patients with DM. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03530176.

Myocardial perfusion imaging for diabetes: Key points from the evidence and clinical questions to be answered.

Diabetes represents a worldwide increasing problem and cardiovascular disease is the most common cause of death in diabetic patients. Pathophysiology that links diabetes to cardiovascular disease is a complex and multifactorial phenomenon evolving over time and involving both large blood vessels (macrovasculature) and small blood vessels (microvasculature). Myocardial perfusion imaging (MPI) imaging by both single-photon emission computer tomography and positron emission tomography with different specific tracers has become an indispensable tool for discriminating normal from diseased myocardial tissues and left ventricular function and monitoring myocardial blood flows, leading to the evaluation of almost overall physiologic consequences of the macro- and microvascular impairment involved in diabetic patients. This review will provide an overview of the role of MPI in the diagnosis and risk assessment of patients with diabetes and suspected or known CAD.

Warranty period of normal stress myocardial perfusion imaging in hypertensive patients: A parametric survival analysis.

BACKGROUND: We evaluated the warranty period of a normal stress myocardial perfusion single-photon emission computed tomography (MPS) in hypertensive patients. METHODS AND RESULTS: A total of 471 consecutive hypertensive patients with suspected coronary artery disease and normal perfusion at stress MPS were followed for a mean of 76 ± 21 months. Endpoint events were cardiac death or nonfatal myocardial infarction. With Cox analysis, age (hazard ratio 1.1, P < .005) and stress test type (hazard ratio 2.7, P < .005) were independent predictors of events. With parametric Weibull analysis, patients ≤60 years old undergoing exercise stress test remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration were observed in those > 60 years old who underwent pharmacologic stress test. In patients undergoing exercise test, peak systolic blood pressure (BP; hazard ratio 1.1, P < .005) emerged as predictor of events, and only subjects with peak systolic BP < 160 mmHg remained at low risk for the entire length of follow-up. In contrast, for patients with peak systolic BP ≥180 mmHg, the time to achieve a cumulative cardiac risk level of 3% was 18 months. CONCLUSIONS: In hypertensive patients, the warranty period of a normal stress MPS varies according to stress type and peak systolic BP. A normal stress MPS can be considered reassuring in subjects ≤60 years old who performed exercise stress test and a peak systolic BP < 160 mmHg.

Aspergillus flavus malignant external otitis in a diabetic patient: case report and literature review.

PURPOSE: Malignant external otitis is an aggressive and potentially life-threatening infection. This rare disorder is typically caused by Pseudomonas aeruginosa and affects almost exclusively elderly diabetic patients. However, fungal malignant external otitis have been identified, especially in immunocompromised hosts. METHODS: We report a rare case of invasive malignant external otitis caused by Aspergillus flavus in a diabetic patient without other underlying immunosuppression. A review of Aspergillus spp. malignant external otitis since voriconazole became the first line for invasive aspergillosis was performed. RESULTS: A 72-year-old man with diabetes mellitus developed invasive malignant external otitis with a vascular involvement. The patient was treated with empiric courses of antibiotics until a fungal infection was diagnosed. Proven Apsergillus infection was based on histopathological examination and isolation of A. flavus from culture of osteo-meningeal biopsies. Despite optimal antimicrobial therapy with voriconazole, the patient presented with cerebral infarction in the setting of an angioinvasive fungal infection leading to a fatal outcome. From a review of the literature, we found 39 previously published cases of proven Aspergillus spp. malignant external otitis treated with new triazoles. CONCLUSION: Given our experience and the literature review, a fungal etiology should be considered early in the course of malignant external otitis unresponsive to a conventional broad spectrum antibiotic therapy, with the need for a tissue biopsy to confirm the diagnosis.

Comparison of Intravascular Ultrasound Virtual Histology Parameters in Diabetes versus Non-Diabetes with Acute Coronary Syndrome.

INTRODUCTION: The progression and pattern of coronary atherosclerosis in diabetes mellitus (DM) is different from non-DM, leading to a higher rate of vascular complications in DM. OBJECTIVE: This study aims to assess and compare the high-risk plaque characteristics in the culprit artery of DM and non-DM patients with acute coronary syndrome (ACS) using virtual histology intravascular ultrasound (VH-IVUS). METHODS: A total of 158 ACS patients were included, 63 of whom were known to have DM. IVUS analysis was done in the de novo target vessel and culprit lesion for which percutaneous coronary intervention was planned. Culprit lesions with a visual-estimate angiographic stenosis of <70% were excluded. RESULTS: The mean age of patients was 52.4 ± 11.6 years. The study group comprised 82% men, 31% with hypertension, and 39.87% with DM. No significant difference was observed between the DM and non-DM groups in relation to quantitative IVUS parameters like lesion length, minimal lumen area, and plaque area. However, there was a significant difference in VH-IVUS parameters like higher necrotic core and dense calcium in the DM patients than in the non-DM patients (p < 0.01). The occurrence of VH-derived thin-cap fibroatheroma (VH-TCFA) in the culprit vessel was significantly higher in the DM group than in the non-DM group (25.3 vs. 5.2%; p < 0.01). Positive vessel-wall remodeling was noted in both groups without any significant difference (p = 0.74). CONCLUSION: The DM patients had high-risk plaque composition features like a higher necrotic core, which is a marker of plaque vulnerability. Thus, aggressive medical therapy targeting vascular inflammation using high-dose statins would help in the stabilization of unstable plaque morphology and the reduction of major cardiovascular events.

Acute hemichorea in a young type 1 diabetic.

Purpose/Aim: Acute movement disorder is an uncommon presenting symptom in patients with diabetes mellitus. We report a 20-year-old lady with poorly controlled type 1 diabetes, who presented with acute hemichorea and was found to have two rare diabetes-related central nervous complications of diabetic striatopathy and severe moyamoya disease (MMD).Materials and methods: She was treated with aggressive glycemic control; clonazepam and tetrabenazine as well as aspirin stroke prophylaxis for her MMD with resolution of her chorea 3 months later. She subsequently underwent cerebral revascularization surgery for her MMD.Results: This case highlights the possible differentials of acute chorea in diabetic patients and explores the pathophysiological mechanisms that may underlie both conditions in patients with type 1 diabetes.Conclusion: We recommend performing both magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) brain for comprehensive evaluation of diabetic patients with new onset chorea. Prompt and accurate diagnosis is crucial as it guides prognostication and treatment strategies.

Incidental findings on brain MRI in a cohort of diabetic patients.

OBJECTIVE: To study the frequency and management of incidental findings in nonenhanced brain MRI of a middle-aged population of type 2 diabetic patients. METHODS: We retrospectively analyzed the results of 289 brain MRI obtained from subjects between 40-75 years recruited from a previous study. Incidental findings were classified into three categories: (1) Vascular findings; (2) neoplastic findings; and (3) others. On the other side, we made a classification of referral findings. To compare our results, we reviewed the prevalence and evidence about management of both incidental and referral findings in other series. RESULTS: We found an overall prevalence of incidental findings of 10.4% (30/289). Incidental findings raised according to age. The most common incidental findings were: 7 vascular (2.4%), 6 calcifications (2.1%), 6 cystic (2.1%) and 5 neoplastic (1.7%) lesions. A percentage of 1.7% (5/289) were referral findings which required further clinical work-up. CONCLUSION: Incidental findings are relatively common in patients with type 2 diabetes. The most frequent are vascular findings, accordance with previous studies. Referral findings are uncommon. Clinical evidence about how to best manage the majority of incidental findings is lacking.

Coronary risk equivalence of diabetes assessed by SPECT-MPI.

BACKGROUND: Several publications and guidelines designate diabetes mellitus (DM) as a coronary artery disease (CAD) risk equivalent. The aim of this investigation was to examine DM cardiac risk equivalence from the perspective of stress SPECT myocardial perfusion imaging (MPI). METHODS AND RESULTS: We examined cardiovascular outcomes (cardiac death or nonfatal MI) of 17,499 patients referred for stress SPECT-MPI. Patients were stratified into four categories: non-DM without CAD, non-DM with CAD, DM without CAD, and DM with CAD, and normal or abnormal perfusion. Cardiac events occurred in 872 (5%), with event-free survival best among non-DM without CAD, worst in DM with CAD, and intermediate in DM without CAD, and non-DM with CAD. After multivariate adjustment, risk remained comparable between DM without CAD and non-DM with CAD [AHR 1.0 (95% CI 0.84-1.28), P =0.74]. Annualized event rates for normal subjects were 1.4% and 1.6% for non-DM with CAD and DM without CAD, respectively (P = 0.48) and 3.5% (P = 0.95) for both abnormal groups. After multivariate adjustment, outcomes were comparable within normal [AHR 1.4 (95% CI 0.98-1.96) P = 0.06] and abnormal [AHR 1.1 (95% CI 0.83-1.50) P = 0.49] MPI. CONCLUSIONS: Diabetic patients without CAD have comparable risk of cardiovascular events as non-diabetic patients with CAD after stratification by MPI results. These findings support diabetes as a CAD equivalent and suggest that MPI provides additional prognostic information in such patients.

Using magnetic resonance diffusion tensor imaging to evaluate renal function changes in diabetic patients with early-stage chronic kidney disease.

AIM: To investigate the clinical value of diffusion tensor imaging (DTI) in assessing renal function changes in diabetic patients with early-stage chronic kidney disease (CKD), and the relationship of DTI parameters with estimated glomerular filtration rate (eGFR) and urinary biomarkers. MATERIALS AND METHODS: Thirty-six patients with diabetes mellitus (DM; 30 CKD stage 1 and 6 CKD stage 2) and 26 healthy control subjects were enrolled. DTI was performed using a clinical 3 T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were calculated from the renal cortex and medulla. The correlation of the DTI parameters with eGFR and urinary biomarkers was evaluated. RESULTS: FA values were significantly reduced in the renal cortex and medulla of DM group compared with the control group (cortical FA, Z=-2.834, p=0.005; medullary FA, t=2.768, p=0.007). In the DM group, FA values in the renal cortex and medulla were positively correlated with eGFR, while FA values in the medulla were negatively correlated with the urinary albumin/creatinine ratio, urinary alpha-1 microglobulin/creatinine ratio, and urinary transferring/creatinine ratio. ADC values in the renal cortex and medulla showed a trend towards an increase in the DM group compared with the control group. CONCLUSIONS: Renal DTI is a promising method for assessing early renal function changes in DM patients.

Utility of Contrast-Enhanced Ultrasound for the Assessment of Skeletal Muscle Perfusion in Diabetes Mellitus: A Meta-Analysis.

BACKGROUND This study evaluated the effectiveness of contrast-enhanced ultrasonography for the assessment of skeletal muscle perfusion in diabetes mellites. MATERIAL AND METHODS Electronic databases (Embase, Google Scholar, Ovid, and PubMed) were searched for required articles, and studies were selected by following pre-determined eligibility criteria. Meta-analyses of mean differences or standardized mean differences (SMD) were performed to evaluate the significance of difference in contrast-enhanced ultrasonography measured muscle perfusion indices between patients with diabetes and healthy individuals or between basal and final values of perfusion indices after insulin manipulation or physical exercise in patients with diabetes or healthy individuals. RESULTS There were 15 studies included, with 279 patients with diabetes and 230 healthy individuals in total. The age of the study patients with diabetes mellitus was 55.8 years (95% CI: 49.6 years, 61.9 years) and these patients had disease for 11.4 years (95% CI: 7.7 years, 15.1 years). The percentage of males in group of patients with diabetes was 66% (95% CI: 49%, 84%), body mass index was 29.4 kg/m² (95% CI: 26.5 kg/m², 32.3 kg/m²), hemoglobin A1c was 7.3% (95% CI: 6.7%, 7.9%), and fasting plasma glucose was 149 kg/m² (95% CI: 118 kg/m², 179 kg/m²). Time to peak intensity after provocation was significantly higher in patients with diabetes than in healthy individuals (SMD 1.18 [95% CI: 0.60, 1.76]; P<0.00001). In patients with diabetes, insulin administration did not improve contrast-enhanced ultrasonography measured muscle perfusion indices but exercise improved muscle perfusion but at a level that was statistically non-significant (SMD between basal and post-exercise values (1.03 [95% CI: -0.14, 2.20]; P=0.08). In healthy individuals, lipids in addition to insulin administration was associated with significantly reduced blood volume and blood flow. CONCLUSIONS Our review showed that the use of contrast-enhanced ultrasonography showed that diabetes mellitus was associated with altered muscle perfusion in which insulin-mediated metabolic changes played an important role.

Dental imaging of trabecular bone structure for systemic disorder screening: A systematic review.

The purpose of this systematic review was to evaluate the potential use of dental imaging assessment of trabecular bone structure in the maxillomandibular complex as an adjuvant screening tool to identify systemic disorders. Five electronic databases and grey literature were searched. Studies were included if they investigated subjects with altered trabecular bone determined by dental radiographs. The QUADAS-2 assessed the risk of bias (RoB) among the studies, while the GRADE determined the strength of evidence. A total of 14 studies that included 1,466 individuals were considered eligible for the qualitative analysis. All studies presented an overall low RoB and low concern regarding applicability. Systemic disorders such as osteoporosis, osteogenesis imperfecta, diabetes, and primary hyperparathyroidism, with their respective control groups, were analyzed among the included studies. Osteoporosis was the condition presenting the most significant results, and 72% of the studies detected changes in the maxillomandibular trabecular bone structure. Studies exploring diabetic edentulous patients found less dense trabecular bone pattern (p < 0.05). In summary, periapical and panoramic radiographs, computed tomography, and cone beam computed tomography imaging could be considered useful for the assessment of the mandibular trabecular bone structure of patients affected by osteoporosis and patients with diabetes.

Predictive factors of recurrent endovascular intervention for cephalic arch stenosis after percutaneous transluminal angioplasty.

OBJECTIVE: Cephalic arch stenosis (CAS) is an important and recurring problem arising in hemodialysis patients because of the requirement for repeated interventions to maintain patency. The aim of this study was to determine predictive factors for recurrence of CAS after successful angioplasty. METHODS: A retrospective, case-control study was conducted at two ambulatory vascular access (VA) centers. All patients with a dysfunctional VA referred for an angiographic procedure and with a documented CAS as evidenced during the endovascular intervention (EI) between January 1, 2013, and December 31, 2015, were enrolled; 15 patients in whom an efficacious intervention was not possible were excluded. The study thus concerned 375 EIs using percutaneous transluminal angioplasty without stent placement on 241 VAs for CAS (9% of all procedures performed) during a 3-year period. Patients were compared regarding the absence (group 1; n = 181) or presence (group 2; n = 60) of recurrent CAS. We defined recurrence as that which occurred within 180 days of the previous successful EI for CAS. Any CAS diagnosed and treated >180 days after a previous one was considered a novel CAS and not a recurrence. Multivariate analysis was performed to determine variables independently associated with recurrence of CAS. Kaplan-Meier analysis was performed for determination of primary and assisted primary patency in this population. RESULTS: The recurrence rate of CAS was high (25%). Patients in both groups had similar demographic characteristics, time on hemodialysis, and mean dialysis dose and access flow rate at referral (P > .05). Multivariate analysis provided a significant discriminatory influence pertaining to diabetes (hazard ratio [HR], 2.054; 95% confidence interval [CI], 1.22-3.46; P = .007), residual stenosis even though it was <30% (HR, 1.86; 95% CI, 1.005-3.439; P = .048), and the finding of an isolated CAS lesion (HR, 0.445; 95% CI, 0.219-0.905; P = .025) in comparing group 1 and group 2. All other variables lost statistical significance on multivariate analysis. Primary patency at 6 months was 72%, increasing to an assisted primary patency of 89% at 6 months. The median durations of primary patency and assisted primary patency were 9.5 months and 15.6 months, respectively. CONCLUSIONS: Multivariate analysis showed that diabetes and residual stenosis (albeit <30%) were predictive of recurrence, whereas the finding of an isolated CAS lesion as opposed to stenoses in multiple locations was shown to be negatively associated with recurrent CAS, appearing to be "protective".

Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes.

Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In the present study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with long-standing Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes. Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology.