|
1
|
Andrés-Rebollo FJS, Cárdenas-Valladolid J, Abanades-Herranz JC, Vich-Pérez P, de Miguel-Yanes JM, Guillán M, Salinero-Fort MA. A different perspective on studying stroke predictors: joint models for longitudinal and time-to-event data in a type 2 diabetes mellitus cohort. Cardiovasc Diabetol 2025; 24:165. [PMID: 40241150 PMCID: PMC12004838 DOI: 10.1186/s12933-025-02713-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Most predictive models rely on risk factors and clinical outcomes assessed simultaneously. This approach does not adequately reflect the progression of health conditions. By employing joint models of longitudinal and survival data, we can dynamically adjust prognosis predictions for individual patients. Our objective was to optimize the prediction of stroke or transient ischemic attack (TIA) via joint models that incorporate all available changes in the predictive variables. METHODS A total of 3442 patients with type 2 diabetes mellitus (T2DM) and no history of stroke, TIA or myocardial infarction were followed for 12 years. Models were constructed independently for men and women. We used proportional hazards regression models to assess the effects of baseline characteristics (excluding longitudinal data) on the risk of stroke/TIA and linear mixed effects models to assess the effects of baseline characteristics on longitudinal data development over time. Both submodels were then combined into a joint model. To optimize the analysis, a univariate analysis was first performed for each longitudinal predictor to select the functional form that gave the best fit via the deviance information criterion. The variables were then entered into a multivariate model using pragmatic criteria, and if they improved the discriminatory ability of the model, the area under the curve (AUC) was used. RESULTS During the follow-up period, 303 patients (8.8%) experienced their first stroke/TIA. Age was identified as an independent predictor among males. Among females, age was positively associated with atrial fibrillation (AF). The final model for males included AF, systolic blood pressure (SBP), and diastolic blood pressure (DBP), with albuminuria and the glomerular filtration rate (GFR) as adjustment variables. For females, the model included AF, blood pressure (BP), and renal function (albuminuria and GFR), with HbA1c and LDL cholesterol as adjustment variables. Both models demonstrated an AUC greater than 0.70. CONCLUSIONS Age, AF, and SBP have been confirmed as significant predictive factors in both sexes, whereas renal function was significant only in women. Interestingly, an increase in DBP may serve as a protective factor in our cohort. These factors were particularly relevant in the last 3-7 years of follow-up.
Collapse
Affiliation(s)
- F J San Andrés-Rebollo
- Las Calesas Health Centre, Madrid, Spain
- Biosanitary Research and Innovation Foundation of Primary Care (FIIBAP), Madrid, Spain
- Frailty, Multimorbidity Patterns and Mortality in the Elderly Population Residing in the Community- Hospital La Paz Institute for Health Research IdiPAZ, Madrid, Spain
| | - J Cárdenas-Valladolid
- Biosanitary Research and Innovation Foundation of Primary Care (FIIBAP), Madrid, Spain
- Frailty, Multimorbidity Patterns and Mortality in the Elderly Population Residing in the Community- Hospital La Paz Institute for Health Research IdiPAZ, Madrid, Spain
- Alfonso X El Sabio University, Madrid, Spain
| | - J C Abanades-Herranz
- Biosanitary Research and Innovation Foundation of Primary Care (FIIBAP), Madrid, Spain
- Monóvar Health Centre, Madrid, Spain
| | - P Vich-Pérez
- Biosanitary Research and Innovation Foundation of Primary Care (FIIBAP), Madrid, Spain
- Los Alpes Health Centre, Madrid, Spain
| | - J M de Miguel-Yanes
- Internal Medicine Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, Madrid, Spain
| | - M Guillán
- Department of Neurology, Neurovascular Unit, Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | - M A Salinero-Fort
- Biosanitary Research and Innovation Foundation of Primary Care (FIIBAP), Madrid, Spain.
- Frailty, Multimorbidity Patterns and Mortality in the Elderly Population Residing in the Community- Hospital La Paz Institute for Health Research IdiPAZ, Madrid, Spain.
- Alfonso X El Sabio University, Madrid, Spain.
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Madrid, Spain.
| |
Collapse
|
|
2
|
Xu L, Lin X, Li T, Wen J, Chen G. Association between prognostic nutritional index and diabetic retinopathy among U.S. diabetic adults in NHANES. Sci Rep 2025; 15:12986. [PMID: 40234618 PMCID: PMC12000458 DOI: 10.1038/s41598-025-96582-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 03/31/2025] [Indexed: 04/17/2025] Open
Abstract
Diabetic retinopathy (DR) is characterized by progressive retinal vascular damage that ultimately causes vision loss. The prognostic nutritional index (PNI), which integrates albumin and lymphocytes, serves as an indicator of an individual's inflammatory response, nutritional condition, and immune system function. This research aimed to explore the possible association between PNI and DR. This was a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. Weighted logistic regression analyses were employed to assess the relationship between PNI and DR prevalence. A total of 4791 adults aged 20 years and older were included in the analysis. Results indicated a statistically significant negative correlation between PNI and DR prevalence. In the fully adjusted model, a one-unit rise in PNI corresponded to a 7% reduction in the probability of DR prevalence. Quartile analysis consistently indicated that individuals in the highest PNI quartile had notably lower odds of DR prevalence compared to those in the lowest quartile. Additionally, smooth curve fitting suggested a nonlinear relationship between PNI and DR. Subgroup analysis reinforced the strength of the inverse association between PNI and DR (all p for interaction > 0.05). This nationally representative study demonstrated a significant inverse relationship between PNI levels and DR prevalence among diabetic adults in the United States. Our findings emphasize the potential role of maintaining optimal PNI values in preventing the development of DR.
Collapse
Affiliation(s)
- Lizhen Xu
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
| | - Xiling Lin
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
| | - Ting Li
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
| | - Junping Wen
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
| | - Gang Chen
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China.
| |
Collapse
|
|
3
|
Xie R, Gao H, Xie H, Xie C, Li T. Impdh1 was identified as a key protein promotes diabetic vasculopathy by intervention of vascular endothelial cell pyroptosis. BMC Cardiovasc Disord 2025; 25:176. [PMID: 40082765 PMCID: PMC11905600 DOI: 10.1186/s12872-025-04604-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 02/24/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Diabetic angiopathy (DA) is a diabetic vascular complication. Pyroptosis is an inflammatory death that plays an important role in the development of DA, but the underlying mechanisms have not been fully elucidated. METHODS The GSE169332 dataset from the Gene Expression Omnibus (GEO) was subjected to single-cell RNA sequencing (scRNA-seq) analysis, and the data of diabetic mice were subjected to bulk RNA-seq. The pathway through which the inflammatory microenvironment participated in the DA was explored by pseudotime analysis and cell-cell communication. DA models were constructed using in vitro mouse models. The histopathological changes in the collected aorta were observed by hematoxylin and eosin (H&E) and Masson staining. The distribution and expression of the phenotypic markers related to pyroptosis in aortic tissues (NLRP3, pro-Caspase1, and GSDMD-N) were observed by immunohistochemistry (IHC) or immunofluorescence (IF) staining. Following the silencing of the expression of high glucose (HG)-induced Impdh1 in endothelial cells (ECs), Impdh1 expression was detected by real-time quantitative reverse transcription PCR (qRT-PCR), and the expression of Impdh1, NLRP3, pro-Caspase1, and GSDMD was detected by IF staining; cell migration was detected by cell scratch assay, cell viability was detected by cell counting kit-8 (CCK-8) assay, and tube formation was detected by tube formation assay; the levels of IL-1β and IL-18 were detected using the enzyme-linked immunosorbent assay (ELISA) kits. RESULTS Impdh1 was identified by scRNA-seq and bulk RNA-seq as a key molecule in the progression of DA associated with pyroptosis of aortic ECs. By constructing mouse models of DA, it was found that silencing Impdh1 can inhibit mouse aortic pyroptosis. Silencing of the expression of HG-induced Impdh1 revealed an effective amelioration of EC damage and pyroptosis. CONCLUSION Impdh1 is identified as a potential pyroptosis-related gene associated with DA by scRNA-seq of GEO data and bulk RNA-seq. Impdh1 protects aortic ECs by inhibiting pyroptosis and inflammation. CLINICAL TRIAL NUMBER Not applicable.
Collapse
Affiliation(s)
- Ruiqiang Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan, China.
| | - Hong Gao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan, China
| | - Hongyan Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan, China
| | - Chunguang Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, Sichuan, China
| | - Tianhao Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| |
Collapse
|
|
4
|
Liu X, Chang Y, Li Y, Liu Y, Chen N, Cui J. Association Between Cardiovascular Health and Retinopathy in US Adults: From NHANES 2005-2008. Am J Ophthalmol 2024; 266:56-67. [PMID: 38762091 DOI: 10.1016/j.ajo.2024.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 04/28/2024] [Accepted: 05/13/2024] [Indexed: 05/20/2024]
Abstract
PURPOSE Investigating the relationship between cardiovascular health (CVH) and retinopathy in the adult population of the United States. DESIGN The cross-sectional study. METHODS The study utilized samples, including the diabetes population, from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008 (N= 4249), to assess cardiovascular health (CVH) using the Life's Essential 8 (LE8) assessment. Retinopathy is determined through imaging assessment by professionals independently grading fundus photographs. Univariable and multivariable weighted logistic regression models, restricted cubic splines (RCS), subgroup analysis and weighted quantile sum (WQS) regression approaches were employed to assess the association between LE8 score-based CVH status and retinopathy. The mediation analysis was conducted to investigate whether serum albumin levels mediated the relationship between LE8 score and retinopathy. RESULTS In a fully adjusted logistic regression model, participants in the moderate and high CVH groups had a 39% (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.43-0.87, P-value = 0.01) and 56% (OR 0.44, 95% CI 0.25-0.77, P-value < 0.001) lower odds of developing retinopathy compared to the low CVH group. The RCS model indicates a significant non-linear relationship between CVH and retinopathy. The WQS regression analysis suggests that blood glucose (47.65%) and blood pressure (19.41%) have the highest weights in relation to retinopathy. Mediation analysis suggests that serum albumin partially mediates the relationship between LE8 scores and retinopathy. CONCLUSION This study demonstrates a significant negative correlation between overall cardiovascular health measured by LE8 scores and retinopathy. Public health strategies that promote achieving optimal cardiovascular health indicators may help reduce the burden of retinal microvascular diseases.
Collapse
Affiliation(s)
- Xiangliang Liu
- From the The First Hospital of Jilin University (X.L., Y.C., Y.L., N.C., J.C.), Changchun, China
| | - Yu Chang
- From the The First Hospital of Jilin University (X.L., Y.C., Y.L., N.C., J.C.), Changchun, China
| | - Yuguang Li
- From the The First Hospital of Jilin University (X.L., Y.C., Y.L., N.C., J.C.), Changchun, China
| | - Yingrui Liu
- Department of Ophthalmology, Shenzhen People's Hospital (Y.L.), Shenzhen, China
| | - Naifei Chen
- From the The First Hospital of Jilin University (X.L., Y.C., Y.L., N.C., J.C.), Changchun, China.
| | - Jiuwei Cui
- From the The First Hospital of Jilin University (X.L., Y.C., Y.L., N.C., J.C.), Changchun, China.
| |
Collapse
|
|
5
|
Zygmunciak P, Stróżna K, Błażowska O, Mrozikiewicz-Rakowska B. Extracellular Vesicles in Diabetic Cardiomyopathy-State of the Art and Future Perspectives. Int J Mol Sci 2024; 25:6117. [PMID: 38892303 PMCID: PMC11172920 DOI: 10.3390/ijms25116117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/24/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Cardiovascular complications are the most deadly and cost-driving effects of diabetes mellitus (DM). One of them, which is steadily attracting attention among scientists, is diabetes-induced heart failure, also known as diabetic cardiomyopathy (DCM). Despite significant progress in the research concerning the disease, a universally accepted definition is still lacking. The pathophysiology of the processes accelerating heart insufficiency in diabetic patients on molecular and cellular levels also remains elusive. However, the recent interest concerning extracellular vesicles (EVs) has brought promise to further clarifying the pathological events that lead to DCM. In this review, we sum up recent investigations on the involvement of EVs in DCM and show their therapeutic and indicatory potential.
Collapse
Affiliation(s)
| | - Katarzyna Stróżna
- Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland; (P.Z.)
| | - Olga Błażowska
- Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland; (P.Z.)
| | - Beata Mrozikiewicz-Rakowska
- Department of Endocrinology, Centre of Postgraduate Medical Education, Marymoncka St. 99/103, 01-813 Warsaw, Poland
| |
Collapse
|
|
6
|
Gales C, Stoica B, Rusu-Zota G, Nechifor M. Montelukast Influence on Lung in Experimental Diabetes. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:749. [PMID: 38792932 PMCID: PMC11123472 DOI: 10.3390/medicina60050749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/27/2024] [Accepted: 04/28/2024] [Indexed: 05/26/2024]
Abstract
Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.
Collapse
Affiliation(s)
- Cristina Gales
- Department of Histology, “Gr T Popa” University of Medicine and Pharmacy, Universitatii 16, 700115 Iasi, Romania;
| | - Bogdan Stoica
- Department of Biochemistry, “Gr T Popa” University of Medicine and Pharmacy, Universitatii 16, 700115 Iasi, Romania
| | - Gabriela Rusu-Zota
- Department of Pharmacology, “Gr T Popa” University of Medicine and Pharmacy, Universitatii 16, 700115 Iasi, Romania;
| | - Mihai Nechifor
- Department of Pharmacology, “Gr T Popa” University of Medicine and Pharmacy, Universitatii 16, 700115 Iasi, Romania;
| |
Collapse
|
|
7
|
Bonora BM, Morieri ML, Marassi M, Cappellari R, Avogaro A, Fadini GP. Improved prediction of long-term kidney outcomes in people with type 2 diabetes by levels of circulating haematopoietic stem/progenitor cells. Diabetologia 2023; 66:2346-2355. [PMID: 37712954 PMCID: PMC10627906 DOI: 10.1007/s00125-023-06002-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 07/25/2023] [Indexed: 09/16/2023]
Abstract
AIM/HYPOTHESIS We examined whether prediction of long-term kidney outcomes in individuals with type 2 diabetes can be improved by measuring circulating levels of haematopoietic stem/progenitor cells (HSPCs), which are reduced in diabetes and are associated with cardiovascular risk. METHODS We included individuals with type 2 diabetes who had a baseline determination of circulating HSPCs in 2004-2019 at the diabetes centre of the University Hospital of Padua and divided them into two groups based on their median value per ml of blood. We collected updated data on eGFR and albuminuria up to December 2022. The primary endpoint was a composite of new-onset macroalbuminuria, sustained ≥40% eGFR decline, end-stage kidney disease or death from any cause. The analyses were adjusted for known predictors of kidney disease in the population with diabetes. RESULTS We analysed 342 participants (67.8% men) with a mean age of 65.6 years. Those with low HSPC counts (n=171) were significantly older and had a greater prevalence of hypertension, heart failure and nephropathy (45.0% vs 33.9%; p=0.036), as evidenced by lower eGFR and higher albuminuria at baseline. During a median follow-up of 6.7 years, participants with high vs low HSPC counts had lower rates of the composite kidney outcome (adjusted HR 0.69 [95% CI 0.49, 0.97]), slower decline in eGFR and a similar increase in albuminuria. Adding the HSPC information to the risk score of the CKD Prognosis Consortium significantly improved discrimination of individuals with future adverse kidney outcomes. CONCLUSIONS/INTERPRETATION HSPC levels predict worsening of kidney function and improve the identification of individuals with type 2 diabetes and adverse kidney outcomes over and beyond a clinical risk score.
Collapse
Affiliation(s)
- Benedetta Maria Bonora
- Department of Medicine, University of Padova, Padua, Italy
- Veneto Institute of Molecular Medicine, Padua, Italy
| | | | | | | | - Angelo Avogaro
- Department of Medicine, University of Padova, Padua, Italy
| | - Gian Paolo Fadini
- Department of Medicine, University of Padova, Padua, Italy.
- Veneto Institute of Molecular Medicine, Padua, Italy.
| |
Collapse
|
|
8
|
Zhou C, She X, Gu C, Hu Y, Ma M, Qiu Q, Sun T, Xu X, Chen H, Zheng Z. FTO fuels diabetes-induced vascular endothelial dysfunction associated with inflammation by erasing m6A methylation of TNIP1. J Clin Invest 2023; 133:e160517. [PMID: 37781923 PMCID: PMC10541204 DOI: 10.1172/jci160517] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/01/2023] [Indexed: 10/03/2023] Open
Abstract
Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl/fl diabetic mice, EC-specific Fto-deficient (EC FtoΔ/Δ) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnip1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-κB and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnip1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-κB network provides potential targets to treat diabetic vascular complications.
Collapse
Affiliation(s)
- Chuandi Zhou
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Xinping She
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Chufeng Gu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Yanan Hu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Mingming Ma
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Qinghua Qiu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Tao Sun
- Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
| | - Xun Xu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Haibing Chen
- Department of Endocrinology and Metabolism, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zhi Zheng
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| |
Collapse
|
|
9
|
Neubauer-Geryk J, Wielicka M, Kozera GM, Bieniaszewski L. Angiogenin Levels and Carotid Intima-Media Thickness in Patients with Type 1 Diabetes and Metabolic Syndrome. Biomedicines 2023; 11:2591. [PMID: 37761032 PMCID: PMC10526946 DOI: 10.3390/biomedicines11092591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 09/29/2023] Open
Abstract
It is well documented that in patients with type 1 diabetes (DM1), decreased levels of angiogenin are associated with the development of overt nephropathy. However, little is known about angiogenin levels and subclinical macrovascular organ damage in patients with DM1 and concomitant metabolic syndrome (MS). Therefore, we analyzed the relationship between angiogenin levels and carotid intima-media thickness (cIMT) in DM1 patients with and without MS. We found that angiogenin concentration was significantly lower in DM1 patients compared to controls, while the cIMT measurements were comparable. Exclusion of patients with MS, patients with hypertension, undergoing treatment, or cigarette smokers did not change these findings. Of note, when comparing the subgroups of DM1 patients with and without MS, there was no significant difference between angiogenin levels. However, we did note a significant difference in these levels after the exclusion of smokers. The comparison of cIMT in these subgroups showed a significant difference between the study subgroups. This difference was no longer observed when the age of the patients was taken into account. In summary, it can be concluded that metabolic syndrome in patients with type 1 diabetes does not appear to impact angiogenin levels or cIMT.
Collapse
Affiliation(s)
- Jolanta Neubauer-Geryk
- Clinical Physiology Unit, Medical Simulation Centre, Medical University of Gdańsk, 80-210 Gdansk, Poland; (M.W.); (G.M.K.); (L.B.)
| | - Melanie Wielicka
- Clinical Physiology Unit, Medical Simulation Centre, Medical University of Gdańsk, 80-210 Gdansk, Poland; (M.W.); (G.M.K.); (L.B.)
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Division of Neonatology, Ann Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA
| | - Grzegorz M. Kozera
- Clinical Physiology Unit, Medical Simulation Centre, Medical University of Gdańsk, 80-210 Gdansk, Poland; (M.W.); (G.M.K.); (L.B.)
| | - Leszek Bieniaszewski
- Clinical Physiology Unit, Medical Simulation Centre, Medical University of Gdańsk, 80-210 Gdansk, Poland; (M.W.); (G.M.K.); (L.B.)
| |
Collapse
|
|
10
|
Condina A, Lykina T. Treatment Outcomes of Diabetic Patients With Erectile Dysfunction Prescribed High-Dose Tadalafil. Cureus 2023; 15:e34812. [PMID: 36915849 PMCID: PMC10008086 DOI: 10.7759/cureus.34812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2023] [Indexed: 02/11/2023] Open
Abstract
Objective: To assess the treatment outcome of diabetic patients with erectile dysfunction who are prescribed an alternate daily high dose of tadalafil over a 120-day treatment period. Methods: This was a single-site, retrospective, observational study of 63 diabetic men with erectile dysfunction prescribed an alternate daily dose of 30mg of tadalafil between January 1, 2021, and December 31, 2021. Treatment outcomes accessed medication compliance, adverse drug reactions, and patient treatment satisfaction at 60- and 120-days treatment. Results: Mean age of patients was 58.3 years and included patients who suffered from comorbidities ranging from hypertension (54.0%), dyslipidemia (52.3%), and depression (9.5%). At 60 days in the study, 69.8% were satisfied and continued the treatment. However, at the end of the 120-treatment period, a low number of men (17.5%) were satisfied with the treatment and therefore did not remain on the treatment protocol. These patients reported a lack of medication dose efficacy (86.5%), non-compliance with treatment as prescribed (65.4%), and adverse drug reactions (30.8%) as reasons for discontinuing treatment. None of the identified patient demographics were significantly associated with 120-day continuous treatment. Similarly, the odds ratio derived from the logistic regression did not demonstrate an association between the selected variables and the outcome of 120-day continuous treatment retention. Conclusion: This retrospective case series study found that 82.5% of diabetic patients were not satisfied with treatment with alternate dosing of 30mg tadalafil to treat their ED at the end of the 120-day treatment period suggesting an alternative treatment plan.
Collapse
Affiliation(s)
| | - Tatiana Lykina
- Allergy and Immunology, Oceania University of Medicine, Samoa, AUS
| |
Collapse
|
|
11
|
Zhang L, Jiang F, Xie Y, Mo Y, Zhang X, Liu C. Diabetic endothelial microangiopathy and pulmonary dysfunction. Front Endocrinol (Lausanne) 2023; 14:1073878. [PMID: 37025413 PMCID: PMC10071002 DOI: 10.3389/fendo.2023.1073878] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 02/17/2023] [Indexed: 04/08/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with a high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by the macrovascular and microvascular bed degradation brought on by metabolic, hemodynamic, and inflammatory variables. However, research in recent years has expanded the target organ in T2DM to include the lung. Inflammatory lung diseases also impose a severe financial burden on global healthcare. T2DM has long been recognized as a significant comorbidity that influences the course of various respiratory disorders and their disease progress. The pathogenesis of the glycemic metabolic problem and endothelial microangiopathy of the respiratory disorders have garnered more attention lately, indicating that the two ailments have a shared history. This review aims to outline the connection between T2DM related endothelial cell dysfunction and concomitant respiratory diseases, including Coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
Collapse
Affiliation(s)
- Lanlan Zhang
- Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Lanlan Zhang, ; Xin Zhang, ; Chuntao Liu,
| | - Faming Jiang
- Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Yingying Xie
- Department of Nephrology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yan Mo
- Department of Neurology Medicine, The Aviation Industry Corporation of China (AVIC) 363 Hospital, Chengdu, China
| | - Xin Zhang
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Lanlan Zhang, ; Xin Zhang, ; Chuntao Liu,
| | - Chuntao Liu
- Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Lanlan Zhang, ; Xin Zhang, ; Chuntao Liu,
| |
Collapse
|
|
12
|
Lu YW, Chang CC, Chou RH, Tsai YL, Liu LK, Chen LK, Huang PH, Lin SJ. Sex difference in the association between pathological albuminuria and subclinical atherosclerosis: insights from the I-Lan longitudinal aging study. Aging (Albany NY) 2022; 14:8001-8012. [PMID: 36227142 PMCID: PMC9596222 DOI: 10.18632/aging.204331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/23/2022] [Indexed: 11/25/2022]
Abstract
Background: Pathological albuminuria (PAU) (urinary albumin creatinine ratio [UACR] ≥30 mg/g) is an independent risk factor of cardiovascular disease. PAU is more prevalent in men than women. We aimed to compare the association of PAU and the early phase of subclinical atherosclerosis (SA) between sexes. Methods: 1228 subjects aged 50–90 years were stratified by sex and UACR (normal or PAU). SA was defined as mean carotid intima-media thickness ≥75th percentile of the cohort. Demographics and SA prevalence were compared between groups. Multivariate logistic regression was performed to assess the relationship between PAU and SA. Results: Both men and women with PAU had increased prevalence of hypertension, anti-hypertensive therapy, and metabolic syndrome than controls. Men with PAU were older and had greater waist circumference and total body fat percentage. Sex disparity was observed in associations between waist-to-height ratio, total body fat, and UACR. After adjusting for traditional risk factors, multivariate logistic regression disclosed that PAU was independently associated with SA in men (adjusted odds ratio 1.867, 95% CI 1.066–3.210) but not in women. Conclusion: The relationship of PAU and SA differed between sexes. This result may highlight the need for sex-specific risk management strategies to prevent atherosclerosis.
Collapse
Affiliation(s)
- Ya-Wen Lu
- Division of Cardiology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chin Chang
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ruey-Hsing Chou
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Lin Tsai
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Li-Kuo Liu
- Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.,Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Liang-Kung Chen
- Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.,Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan
| | - Po-Hsun Huang
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shing-Jong Lin
- Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan.,Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.,Division of Cardiology, Heart Center, Cheng-Hsin General Hospital, Taipei, Taiwan
| |
Collapse
|
|
13
|
Munteanu C, Rotariu M, Turnea MA, Anghelescu A, Albadi I, Dogaru G, Silișteanu SC, Ionescu EV, Firan FC, Ionescu AM, Oprea C, Onose G. Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy. Curr Issues Mol Biol 2022; 44:3378-3397. [PMID: 36005129 PMCID: PMC9406839 DOI: 10.3390/cimb44080233] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/10/2022] [Accepted: 07/11/2022] [Indexed: 12/14/2022] Open
Abstract
Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium-which is a dynamic endocrine organ with autocrine and paracrine activity-regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science.
Collapse
Affiliation(s)
- Constantin Munteanu
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700454 Iași, Romania; (M.R.); (M.-A.T.)
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania;
| | - Mariana Rotariu
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700454 Iași, Romania; (M.R.); (M.-A.T.)
| | - Marius-Alexandru Turnea
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700454 Iași, Romania; (M.R.); (M.-A.T.)
| | - Aurelian Anghelescu
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania;
- Faculty of Midwives and Nursing, University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania
| | - Irina Albadi
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania; (I.A.); (E.V.I.); (C.O.)
- Teaching Emergency County Hospital “Sf. Apostol Andrei”, 900591 Constanta, Romania
| | - Gabriela Dogaru
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Clinical Rehabilitation Hospital, 400437 Cluj-Napoca, Romania
| | - Sînziana Calina Silișteanu
- Faculty of Medicine and Biological Sciences, “Stefan cel Mare” University of Suceava, 720229 Suceava, Romania;
| | - Elena Valentina Ionescu
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania; (I.A.); (E.V.I.); (C.O.)
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | | | - Anca Mirela Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania;
| | - Carmen Oprea
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania; (I.A.); (E.V.I.); (C.O.)
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | - Gelu Onose
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania;
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania;
| |
Collapse
|
|
14
|
Munteanu C, Rotariu M, Turnea M, Dogaru G, Popescu C, Spînu A, Andone I, Postoiu R, Ionescu EV, Oprea C, Albadi I, Onose G. Recent Advances in Molecular Research on Hydrogen Sulfide (H 2S) Role in Diabetes Mellitus (DM)-A Systematic Review. Int J Mol Sci 2022; 23:ijms23126720. [PMID: 35743160 PMCID: PMC9223903 DOI: 10.3390/ijms23126720] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/10/2022] [Accepted: 06/13/2022] [Indexed: 02/01/2023] Open
Abstract
Abundant experimental data suggest that hydrogen sulfide (H2S) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the H2S biological actions; however, H2S is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of H2S have been identified, either based on H2S exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of H2S in DM. This review was conducted following the “Preferred reporting items for systematic reviews and meta-analyses” (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/“syntaxes” used contextually, over the last five years (2017–2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous H2S releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of H2S as a therapeutic agent is still at the beginning.
Collapse
Affiliation(s)
- Constantin Munteanu
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700115 Iași, Romania; (M.R.); (M.T.)
- Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania; (C.P.); (A.S.); (I.A.); (R.P.)
- Correspondence: (C.M.); (G.O.)
| | - Mariana Rotariu
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700115 Iași, Romania; (M.R.); (M.T.)
| | - Marius Turnea
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700115 Iași, Romania; (M.R.); (M.T.)
| | - Gabriela Dogaru
- Clinical Rehabilitation Hospital, 400066 Cluj-Napoca, Romania;
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania
| | - Cristina Popescu
- Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania; (C.P.); (A.S.); (I.A.); (R.P.)
| | - Aura Spînu
- Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania; (C.P.); (A.S.); (I.A.); (R.P.)
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
| | - Ioana Andone
- Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania; (C.P.); (A.S.); (I.A.); (R.P.)
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
| | - Ruxandra Postoiu
- Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania; (C.P.); (A.S.); (I.A.); (R.P.)
| | - Elena Valentina Ionescu
- Faculty of Medicine, Ovidius University of Constanta, 900527 Constanta, Romania; (E.V.I.); (C.O.); (I.A.)
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | - Carmen Oprea
- Faculty of Medicine, Ovidius University of Constanta, 900527 Constanta, Romania; (E.V.I.); (C.O.); (I.A.)
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | - Irina Albadi
- Faculty of Medicine, Ovidius University of Constanta, 900527 Constanta, Romania; (E.V.I.); (C.O.); (I.A.)
- Teaching Emergency County Hospital “Sf. Apostol Andrei” Constanta, 900591 Constanta, Romania
| | - Gelu Onose
- Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania; (C.P.); (A.S.); (I.A.); (R.P.)
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
- Correspondence: (C.M.); (G.O.)
| |
Collapse
|
|
15
|
Takenouchi Y, Seki Y, Shiba S, Ohtake K, Nobe K, Kasono K. Effects of dietary palmitoleic acid on vascular function in aorta of diabetic mice. BMC Endocr Disord 2022; 22:103. [PMID: 35436932 PMCID: PMC9014575 DOI: 10.1186/s12902-022-01018-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/22/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Chronic hyperglycemia in diabetes causes atherosclerosis and progresses to diabetic macroangiopathy, and can lead to coronary heart disease, myocardial infarction and cerebrovascular disease. Palmitoleic acid (POA) is a product of endogenous lipogenesis and is present in fish and vegetable oil. In human and animal studies, POA is reported as a beneficial fatty acid related to insulin sensitivity and glucose tolerance. However, few studies have reported its effects on aortic function in diabetes. Here, we investigated the effects of POA administration on vascular function in KKAy mice, a model of type 2 diabetes. METHODS Male C57BL/6 J (control) and KKAy (experimental) mice at the age of 14 weeks were used in the present study. For each mouse strain, one group was fed with reference diet and a second group was fed POA-containing diet for 2 weeks. The vascular reactivities of prepared aortic rings were then measured in an organ bath to determine if POA administration changed vascular function in these mice. RESULTS KKAy mice treated with POA exhibited decreased plasma glucose levels compared with mice treated with reference diet. However, endothelium-dependent vasorelaxant responses to acetylcholine and protease-activated receptor 2 activating protein, which are attenuated in the aorta of KKAy mice compared to C57BL/6 J mice under a reference diet, were not affected by a 2-week POA treatment. In addition, assessment of vasoconstriction revealed that the phenylephrine-induced vasoconstrictive response was enhanced in KKAy mice compared to C57BL/6 J mice under a reference diet, but no effect was observed in KKAy mice fed a POA-containing diet. In contrast, there was an increase in vasoconstriction in C57BL/6 J mice fed the POA-containing diet compared to mice fed a reference diet. Furthermore, the vasoconstriction in aorta in both C57BL/6 J and KKAy mice fed a POA-containing diet were further enhanced under hyperglycemic conditions compared to normal glucose conditions in vitro. In the hyperinsulinemic, and hyperinsulinemic combined with hyperglycemic conditions, vasoconstriction was increased in KKAy mice fed with POA. CONCLUSION These results suggest that POA intake enhances vasoconstriction under hyperglycemic and hyperinsulinemic conditions, which are characteristics of type 2 diabetes, and may contribute to increased vascular complications in diabetes.
Collapse
Affiliation(s)
- Yasuhiro Takenouchi
- Department of Pharmacology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
| | - Yoshie Seki
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Sachiko Shiba
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Kazuo Ohtake
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Koji Nobe
- Division of Pharmacology, Department of Pharmacology, Toxicology Therapeutics, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, 142-8555, Japan
| | - Keizo Kasono
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
| |
Collapse
|
|
16
|
Cui Y, Zhang H, Zhu J, Liao Z, Wang S, Liu W. Correlations of Salivary and Blood Glucose Levels among Six Saliva Collection Methods. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19074122. [PMID: 35409805 PMCID: PMC8999001 DOI: 10.3390/ijerph19074122] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 02/07/2023]
Abstract
Background: Saliva has been studied as a better indicator of disorders and diseases than blood. Specifically, the salivary glucose level is considered to be an indicator of diabetes mellitus (DM). However, saliva collection methods can affect the salivary glucose level, thereby affecting the correlation between salivary glucose and blood glucose. Therefore, this study aims to identify an ideal saliva collection method and to use this method to determine the population and individual correlations between salivary glucose and blood glucose levels in DM patients and healthy controls. Finally, an analysis of the stability of the individual correlations is conducted. Methods: This study included 40 age-matched DM patients and 40 healthy controls. In the fasting state, saliva was collected using six saliva collection methods, venous blood was collected simultaneously from each study participant, and both samples were analyzed at the same time using glucose oxidase peroxidase. A total of 20 DM patients and 20 healthy controls were arbitrarily selected from the above participants for one week of daily testing. The correlations between salivary glucose and blood glucose before and after breakfast were analyzed. Finally, 10 DM patients and 10 healthy controls were arbitrarily selected for one month of daily testing to analyze the stability of individual correlations. Results: Salivary glucose levels were higher in DM patients than healthy controls for the six saliva collection methods. Compared with unstimulated saliva, stimulated saliva had decreased glucose level and increased salivary flow. In addition, unstimulated parotid salivary glucose was most correlated with blood glucose level (R2 = 0.9153), and the ROC curve area was 0.9316, which could accurately distinguish DM patients. Finally, it was found that the correlations between salivary glucose and blood glucose in different DM patients were quite different. The average correlation before breakfast was 0.83, and the average correlation after breakfast was 0.77. The coefficient of variation of the correlation coefficient before breakfast within 1 month was less than 5%. Conclusion: Unstimulated parotid salivary glucose level is the highest and is most correlated with blood glucose level, which can be accurately used to distinguish DM patients. Meanwhile, the correlation between salivary glucose and blood glucose was found to be relatively high and stable before breakfast. In general, the unstimulated parotid salivary glucose before breakfast presents an ideal saliva collecting method with which to replace blood-glucose use to detect DM, which provides a reference for the prediction of DM.
Collapse
Affiliation(s)
- Yangyang Cui
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (Y.C.); (H.Z.); (J.Z.)
- Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
- Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China;
| | - Hankun Zhang
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (Y.C.); (H.Z.); (J.Z.)
- Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China;
| | - Jia Zhu
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (Y.C.); (H.Z.); (J.Z.)
- Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
- Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China;
| | - Zhenhua Liao
- Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China;
| | - Song Wang
- Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China;
- Correspondence: (S.W.); (W.L.); Tel.: +86-0755-26558633 (S.W.); +86-0755-26551376 (W.L.)
| | - Weiqiang Liu
- Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (Y.C.); (H.Z.); (J.Z.)
- Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
- Biomechanics and Biotechnology Lab, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China;
- Correspondence: (S.W.); (W.L.); Tel.: +86-0755-26558633 (S.W.); +86-0755-26551376 (W.L.)
| |
Collapse
|
|
17
|
Yang J, Liu D, Liu Z. Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients. Front Endocrinol (Lausanne) 2022; 13:830466. [PMID: 35399949 PMCID: PMC8991685 DOI: 10.3389/fendo.2022.830466] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/07/2022] [Indexed: 01/07/2023] Open
Abstract
Background The prevalence of diabetic microvascular diseases has increased significantly worldwide, the most common of which are diabetic nephropathy (DN) and diabetic retinopathy (DR). Microvascular endothelial cells are thought to be major targets of hyperglycemic damage, while the underlying mechanism of diffuse endothelial dysfunction in multiple organs needs to be further investigated. Aim The aim of this study is to explore the endothelial dysfunction mechanisms of serum exosomes (SExos) extracted from DR and DN (DRDN) patients. Methods In this study, human glomerular endothelial cells (HGECs) were used as the cell model. Metabolomics ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and proteomics tandem mass tag (TMT)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) together with bioinformatics, the correlation analysis, and the joint pathway analysis were employed to discover the underlying mechanisms of endothelial dysfunction caused by patient's SExos. Results It can be assumed that serum exosomes extracted by DRDN patients might cause endothelial dysfunction mainly by upregulating alpha subunit of the coagulation factor fibrinogen (FIBA) and downregulating 1-methylhistidine (1-MH). Bioinformatics analysis pointed to an important role in reducing excess cysteine and methionine metabolism. Conclusion FIBA overexpression and 1-MH loss may be linked to the pathogenicity of diabetic endothelial dysfunction in DR/DN, implying that a cohort study is needed to further investigate the role of FIBA and 1-MH in the development of DN and DR, as well as the related pathways between the two proteins.
Collapse
Affiliation(s)
- Jing Yang
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China
- Henan Province Research Center for Kidney Disease, Zhengzhou, China
- Key Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease in Henan Province, Zhengzhou, China
| | - Dongwei Liu
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China
- Henan Province Research Center for Kidney Disease, Zhengzhou, China
- Key Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease in Henan Province, Zhengzhou, China
- Department of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhangsuo Liu
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China
- Henan Province Research Center for Kidney Disease, Zhengzhou, China
- Key Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease in Henan Province, Zhengzhou, China
- Department of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
18
|
Basra R, Whyte M, Karalliedde J, Vas P. What is the impact of microvascular complications of diabetes on severe COVID-19? Microvasc Res 2022; 140:104310. [PMID: 34979154 PMCID: PMC8719364 DOI: 10.1016/j.mvr.2021.104310] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/24/2021] [Accepted: 12/27/2021] [Indexed: 02/07/2023]
Abstract
Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.
Collapse
Affiliation(s)
- Ruman Basra
- School of Cardiovascular Medicine & Sciences, King's College London, London, UK
| | - Martin Whyte
- Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK,Department of Diabetes, King's College NHS Foundation Trust, London, UK,King's Health Partners' Institute of Diabetes, Endocrinology and Obesity, London, UK
| | - Janaka Karalliedde
- School of Cardiovascular Medicine & Sciences, King's College London, London, UK,King's Health Partners' Institute of Diabetes, Endocrinology and Obesity, London, UK
| | - Prashanth Vas
- Department of Diabetes, King's College NHS Foundation Trust, London, UK,King's Health Partners' Institute of Diabetes, Endocrinology and Obesity, London, UK,Corresponding author at: Department of Diabetes, King's College Hospital, London SE5 9RS, UK
| |
Collapse
|
|
19
|
Jansson Sigfrids F, Stechemesser L, Dahlström EH, Forsblom CM, Harjutsalo V, Weitgasser R, Taskinen MR, Groop PH. Apolipoprotein C-III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria. J Intern Med 2022; 291:338-349. [PMID: 34817888 PMCID: PMC9298713 DOI: 10.1111/joim.13412] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVES We studied apolipoprotein C-III (apoC-III) in relation to diabetic kidney disease (DKD), cardiovascular outcomes, and mortality in type 1 diabetes. METHODS The cohort comprised 3966 participants from the prospective observational Finnish Diabetic Nephropathy Study. Progression of DKD was determined from medical records. A major adverse cardiac event (MACE) was defined as acute myocardial infarction, coronary revascularization, stroke, or cardiovascular mortality through 2017. Cardiovascular and mortality data were retrieved from national registries. RESULTS ApoC-III predicted DKD progression independent of sex, diabetes duration, blood pressure, HbA1c , smoking, LDL-cholesterol, lipid-lowering medication, DKD category, and remnant cholesterol (hazard ratio [HR] 1.43 [95% confidence interval 1.05-1.94], p = 0.02). ApoC-III also predicted the MACE in a multivariable regression analysis; however, it was not independent of remnant cholesterol (HR 1.05 [0.81-1.36, p = 0.71] with remnant cholesterol; 1.30 [1.03-1.64, p = 0.03] without). DKD-specific analyses revealed that the association was driven by individuals with albuminuria, as no link between apoC-III and the outcome was observed in the normal albumin excretion or kidney failure categories. The same was observed for mortality: Individuals with albuminuria had an adjusted HR of 1.49 (1.03-2.16, p = 0.03) for premature death, while no association was found in the other groups. The highest apoC-III quartile displayed a markedly higher risk of MACE and death than the lower quartiles; however, this nonlinear relationship flattened after adjustment. CONCLUSIONS The impact of apoC-III on MACE risk and mortality is restricted to those with albuminuria among individuals with type 1 diabetes. This study also revealed that apoC-III predicts DKD progression, independent of the initial DKD category.
Collapse
Affiliation(s)
- Fanny Jansson Sigfrids
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Lars Stechemesser
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,First Department of Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Emma H Dahlström
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Carol M Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,National Institute for Health and Welfare, Helsinki, Finland
| | - Raimund Weitgasser
- First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.,Department of Medicine, Diabetology, Wehrle-Diakonissen Hospital, Salzburg, Austria
| | | | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | -
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
| |
Collapse
|
|
20
|
Wang C, Sun Y, Liu W, Liu Y, Afzal S, Grover J, Chang D, Münch G, Li CG, Lin S, Chen J, Zhang Y, Cheng Z, Lin Y, Zheng Y, Huang M, Zhou X. Protective effect of the curcumin-baicalein combination against macrovascular changes in diabetic angiopathy. Front Endocrinol (Lausanne) 2022; 13:953305. [PMID: 36060932 PMCID: PMC9433877 DOI: 10.3389/fendo.2022.953305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/04/2022] [Indexed: 12/13/2022] Open
Abstract
Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats.
Collapse
Affiliation(s)
- Chenxiang Wang
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yibin Sun
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Wenjing Liu
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yang Liu
- NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia
| | - Sualiha Afzal
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
| | - Jahnavi Grover
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
| | - Dennis Chang
- NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia
| | - Gerald Münch
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
| | - Chun Guang Li
- NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia
| | - Shiling Lin
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Jianyu Chen
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yiping Zhang
- Third Institute of Oceanography, Technical Innovation Center for Utilization of Marine Biological Resources, Ministry of Natural Resources, Xiamen, China
| | - Zaixing Cheng
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yanxiang Lin
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yanfang Zheng
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- *Correspondence: Yanfang Zheng, ; Mingqing Huang, ; Xian Zhou,
| | - Mingqing Huang
- Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- *Correspondence: Yanfang Zheng, ; Mingqing Huang, ; Xian Zhou,
| | - Xian Zhou
- NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia
- *Correspondence: Yanfang Zheng, ; Mingqing Huang, ; Xian Zhou,
| |
Collapse
|
|
21
|
Ulutas HG, Guclu M, Aslanci ME, Karatas G. The relationship between carotid intima-media thickness and microvascular changes in retinal zones and optic disc in patients with type 1 diabetes mellitus. Eur J Ophthalmol 2021; 32:2328-2337. [PMID: 34851200 DOI: 10.1177/11206721211064024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE The aim of this study was to detect early retinal vascular changes with optical coherence tomography angiography (OCTA) in type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy and to evaluate the correlation of the results with carotid intima-media thickness (IMT). DESIGN This is a case-control and cross-sectional study. METHODS This study included 38 adult patients with T1DM, and 38 age and gender-matched healthy controls. Retinal and optic disc (OD) measurements were taken using OCTA. The carotid artery IMT of each patient was measured using Doppler ultrasonography. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density, foveal avascular zone (FAZ), non-flow area (NFA) and foveal density (FD) were analysed in the fovea centred 6 × 6 mm macular area. The superficial capillary plexus and DCP were also scanned centred on the peripapillary region. The correlations between OCTA measurements and carotid IMT, duration of DM and haemoglobin A1c levels in patients with T1DM were evaluated. RESULTS The mean values for carotid IMT were significantly higher in diabetic patients than in controls (p < 0.001). The mean values for vessel density SCP, DCP and OD were significantly lower in the diabetic group (p < 0.05). There were correlations between the carotid IMT and duration of T1DM and the evaluated parameters of OCTA. CONCLUSION Microvascular changes in the SCP and DCP in patients with T1DM without DR offer important data. OCTA can be used to detect early microvascular changes in patients with T1DM without DR. In addition, a relationship was found between SCP vascular dropout and carotid IMT.
Collapse
Affiliation(s)
- Hafize Gokben Ulutas
- Department of Ophthalmology, University of Health Sciences, 147003Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Metin Guclu
- Department of Endocrinology, University of Health Sciences, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Mehmet Emin Aslanci
- Department of Ophthalmology, University of Health Sciences, 147003Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Gokhan Karatas
- Department of Radiology, University of Health Sciences, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| |
Collapse
|
|
22
|
Gamma Irradiation Assisted the Sol–Gel Method for Silver Modified-Nickel Molybdate Nanoparticles Synthesis: Unveiling the Antimicrobial, and Antibiofilm Activities Against Some Pathogenic Microbes. J Inorg Organomet Polym Mater 2021. [DOI: 10.1007/s10904-021-02132-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
23
|
Su YC, Chung CH, Ke MJ, Chen LC, Chien WC, Wu YT. Increased risk of shoulder calcific tendinopathy in diabetes mellitus: A nationwide, population-based, matched cohort study. Int J Clin Pract 2021; 75:e14549. [PMID: 34142423 DOI: 10.1111/ijcp.14549] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/21/2021] [Accepted: 06/13/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Calcific tendinopathy of the rotator cuff is a common cause of painful disability in the shoulder with unclear aetiology. Diabetes mellitus (DM) is associated with calcific tendinopathy; however, large epidemiological data are lacking. Thus, we conducted a nationwide population-based matched cohort study to investigate the risk for calcific tendinopathy of the shoulder in diabetic patients. METHODS The National Health Insurance Research Database of Taiwan was used to include 42 915 patients newly diagnosed with DM between 1 January 2000 and 31 December 2015 and randomly extract the data of 171 660 individuals, as a matched control group. All individuals were followed-up until the development of calcific tendinopathy or the end of 2015. RESULTS Overall, 122 patients from the DM group (0.284%) developed calcific tendinopathy compared with 340 individuals from the non-DM group (0.198%). The Kaplan-Meier analysis indicated that patients with DM had a higher risk of calcific tendinopathy since the eighth year of follow-up (log-rank test, P = .006). Cox proportional hazard regression revealed that the adjusted hazard ratio of calcific tendinopathy in diabetic patients to that in non-diabetic patients was 1.276 (95% confidence interval 1.037-1.571, P = .002). Moreover, the stratified analysis disclosed that DM was a strong independent risk factor for calcific tendinopathy irrespective of the existing comorbidities. CONCLUSIONS This study demonstrated that patients with DM had a 27% increased risk of developing calcific tendinopathy of the shoulder, 8 years after initially being diagnosed with DM.
Collapse
Affiliation(s)
- Yu-Chi Su
- Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Hsiang Chung
- Department of Medical Research, School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association (TIPSPA), Taipei, Taiwan
| | | | - Liang-Cheng Chen
- Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Wu-Chien Chien
- Department of Medical Research, School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Yung-Tsan Wu
- Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Integrated Pain Management Center, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
| |
Collapse
|
|
24
|
Sørensen MH, Bojer AS, Broadbent DA, Plein S, Madsen PL, Gæde P. Cardiac perfusion, structure, and function in type 2 diabetes mellitus with and without diabetic complications. Eur Heart J Cardiovasc Imaging 2021; 21:887-895. [PMID: 31642902 DOI: 10.1093/ehjci/jez266] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/08/2019] [Accepted: 10/12/2019] [Indexed: 12/28/2022] Open
Abstract
AIMS Coronary microvascular disease (CMD) is a known complication in type 2 diabetes mellitus (T2DM). We examined the relationship between diabetic complications, left ventricular (LV) function and structure and myocardial perfusion reserve (MPR) as indicators of CMD in patients with T2DM and control subjects. METHODS AND RESULTS This was a cross-sectional study of 193 patients with T2DM and 25 controls subjects. Patients were grouped as uncomplicated diabetes (n = 71) and diabetes with complications (albuminuria, retinopathy, and autonomic neuropathy). LV structure, function, adenosine stress, and rest myocardial perfusion were evaluated by cardiovascular magnetic resonance. Echocardiography was used to evaluate diastolic function. Patients with uncomplicated T2DM did not have significantly different LV mass and E/e* but decreased MPR (3.8 ± 1.0 vs. 5.1 ± 1.5, P < 0.05) compared with controls. T2DM patients with albuminuria and retinopathy had decreased MPR (albuminuria: 2.4 ± 0.9 and retinopathy 2.6 ± 0.7 vs. 3.8 ± 1.0, P < 0.05 for both) compared with uncomplicated T2DM patients, along with significantly higher LV mass (149 ± 39 and 147 ± 40 vs. 126 ± 33 g, P < 0.05) and E/e* (8.3 ± 2.8 and 8.1 ± 2.2 vs. 7.0 ± 2.5, P < 0.05). When entered in a multiple regression model, reduced MPR was associated with increasing E/e* and albuminuria and retinopathy were associated with reduced MPR. CONCLUSIONS Patients with uncomplicated T2DM have reduced MPR compared with control subjects, despite equivalent LV mass and E/e*. T2DM patients with albuminuria or retinopathy have reduced MPR and increased LV mass and E/e* compared with patients with uncomplicated T2DM. E/e* and MPR are significantly associated after adjustment for age, hypertension, and LV mass, suggesting a link between CMD and cardiac diastolic function. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.org. Unique identifier: NCT02684331.
Collapse
Affiliation(s)
- Martin Heyn Sørensen
- Department of Cardiology and Endocrinology, Slagelse Hospital, Ingemannsvej 32, 4200 Slagelse, Denmark.,Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark
| | - Annemie Stege Bojer
- Department of Cardiology and Endocrinology, Slagelse Hospital, Ingemannsvej 32, 4200 Slagelse, Denmark.,Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark
| | - David Andrew Broadbent
- Department of Medical Physics and Engineering, Leeds Teaching Hospitals NHS Trust, Great George St, LS1 3EX, Leeds, UK.,Biomedical Imaging Science Department, University of Leeds, LS2 9JT, Leeds, UK
| | - Sven Plein
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, LS2 9JT, Leeds, UK
| | - Per Lav Madsen
- Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Capital Region of Denmark, Borgmester Ib Juels Vej 1, 2730 Herlev, Denmark.,Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
| | - Peter Gæde
- Department of Cardiology and Endocrinology, Slagelse Hospital, Ingemannsvej 32, 4200 Slagelse, Denmark.,Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark
| |
Collapse
|
|
25
|
Kaze AD, Santhanam P, Erqou S, Ahima RS, Bertoni A, Echouffo-Tcheugui JB. Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus. J Am Heart Assoc 2021; 10:e018998. [PMID: 34107742 PMCID: PMC8477890 DOI: 10.1161/jaha.120.018998] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Background Microvascular disease (MVD) is a potential contributor to the pathogenesis of diabetes mellitus-related cardiac dysfunction. However, there is a paucity of data on the link between MVD and incident heart failure (HF) in type 2 diabetes mellitus. We examined the association of MVD with incident HF in adults with type 2 diabetes mellitus. Methods and Results A total of 4095 participants with type 2 diabetes mellitus and free of HF were assessed for diabetes mellitus-related MVD including nephropathy, retinopathy, or neuropathy at baseline in the Look AHEAD (Action for Health in Diabetes) study. Incident HF events were prospectively assessed and adjudicated using hospital and death records. Cox models were used to generate hazard ratios and 95% CIs for HF. Of 4095 participants, 34.8% (n=1424) had MVD, defined as the presence of ≥1 of nephropathy, retinopathy, or neuropathy at baseline. Over a median of 9.7 years, there were 117 HF events. After adjusting for relevant confounders, participants with MVD had a 2.5-fold higher risk of incident HF than those without MVD (hazard ratio, 2.54; 95% CI, 1.73-3.75). This association remained significant after additional adjustment for interval development of coronary artery disease (hazard ratio, 2.42; 95% CI, 1.64-3.57). The hazard ratios for HF by type of MVD were 2.22 (95% CI, 1.51-3.27), 1.30 (95% CI, 0.72-2.36), and 1.33 (95% CI, 0.86-2.07) for nephropathy, retinopathy, and neuropathy, respectively. CONCLUSIONS MVD is associated with an excess HF risk in individuals with type 2 diabetes mellitus after adjusting for other known risk factors. Our findings underscore the contribution of MVD to the development of diabetes mellitus-related HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953.
Collapse
Affiliation(s)
- Arnaud D Kaze
- Department of Medicine University of Maryland Medical Center Baltimore MD
| | - Prasanna Santhanam
- Division of Endocrinology, Diabetes & Metabolism Johns Hopkins School of Medicine Baltimore MD
| | - Sebhat Erqou
- Department of Medicine Providence VA Medical Center and Alpert Medical School of Brown University Providence RI
| | - Rexford S Ahima
- Division of Endocrinology, Diabetes & Metabolism Johns Hopkins School of Medicine Baltimore MD
| | - Alain Bertoni
- Department of Epidemiology and Prevention Wake Forest University School of Medicine Winston-Salem NC
| | - Justin B Echouffo-Tcheugui
- Division of Endocrinology, Diabetes & Metabolism Johns Hopkins School of Medicine Baltimore MD.,Welch Prevention Center for Prevention, Epidemiology and Clinical Research Johns Hopkins University Baltimore MD
| |
Collapse
|
|
26
|
Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging. Transplantation 2021; 106:280-288. [PMID: 33908383 DOI: 10.1097/tp.0000000000003803] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase (PDE) 5 inhibitor, tadalafil. METHODS Wild-type (WT) and eNOS knockout (eNOS-KO) mice, a model of endothelial dysfunction, were used to establish in vivo real-time imaging in living mouse kidneys. Neutrophils were labeled green with Ly-6G monoclonal antibody, and plasma flow was labeled red with bovine serum albumin. Tadalafil was administered orally 1 h before surgery. Both kidney pedicles were reperfused after 37° warm ischemia for 45 min. RESULTS Our novel approach revealed that neutrophils were trapped in glomerulus within a few minutes after reperfusion. They gradually increased over time and Infiltrated neutrophils were observed in the tubular lumen and peritubular capillary. The neutrophils were clearly visualized rolling on peritubular capillary plexus at 3 μm/min. The administration of tadalafil significantly reduced neutrophil influx into the glomerulus in both WT and eNOS-KO mice. Reduced neutrophil infiltration in tadalafil groups, which was confirmed by flow cytometry, resulted in histopathologically decreased tubular injury. The expression of VCAM-1 and KIM-1 was partially prevented by tadalafil. CONCLUSIONS Use of a novel technique contributed to elucidation of neutrophil dynamics after reperfusion. Tadalafil has a potential for inhibiting neutrophil infiltration in renal IRI.Supplemental Visual Abstract; http://links.lww.com/TP/C223.
Collapse
|
|
27
|
Sadasivam R, Packirisamy G, Shakya S, Goswami M. Non-invasive multimodal imaging of Diabetic Retinopathy: A survey on treatment methods and Nanotheranostics. Nanotheranostics 2021; 5:166-181. [PMID: 33564616 PMCID: PMC7868006 DOI: 10.7150/ntno.56015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022] Open
Abstract
Diabetes Retinopathy (DR) is one of the most prominent microvascular complications of diabetes. It is one of the pre-eminent causes for vision impairment followed by blindness among the working-age population worldwide. The de facto cause for DR remains challenging, despite several efforts made to unveil the mechanism underlying the pathology of DR. There is quite less availability of the low cost pre-emptive theranostic imaging tools in terms of in-depth resolution, due to the multiple factors involved in the etiology of DR. This review work comprehensively explores the various reports and research works on all perspectives of diabetic retinopathy (DR), and its mechanism. It also discusses various advanced non-destructive imaging modalities, current, and future treatment approaches. Further, the application of various nanoparticle-based drug delivery strategies used for the treatment of DR are also discussed. In a nutshell, the present review work bolsters the pursuit of the development of an advanced non-invasive optical imaging modal with a nano-theranostic approach for the future diagnosis and treatment of DR and its associated ocular complications.
Collapse
Affiliation(s)
- Rajkumar Sadasivam
- Divyadrishti Imaging Laboratory, Department of Physics, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand-247667, India
| | - Gopinath Packirisamy
- Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand-247667, India
| | - Snehlata Shakya
- Department of clinical physiology, Lund University, Skåne University Hospital, Skåne, Sweden
| | - Mayank Goswami
- Divyadrishti Imaging Laboratory, Department of Physics, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand-247667, India
| |
Collapse
|
|
28
|
Protective Effect of Astragaloside IV on High Glucose-Induced Endothelial Dysfunction via Inhibition of P2X7R Dependent P38 MAPK Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5070415. [PMID: 33014270 PMCID: PMC7512101 DOI: 10.1155/2020/5070415] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 08/10/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022]
Abstract
Vascular endothelial dysfunction is associated with increased mortality in patients with diabetes. Astragaloside IV (As-IV) is a bioactive saponin with therapeutic potential as an anti-inflammatory and antiendothelial dysfunction. However, the underlying mechanism for how As-IV ameliorated endothelial dysfunction is still unclear. Therefore, in this study, we examined the protective effect of As-IV against endothelial dysfunction and explored potential molecular biology mechanism. In vivo, rats were intraperitoneally injected with streptozotocin (STZ) at a dose of 65 mg/kg body weight to establish a diabetic model. In vitro studies, rat aortic endothelial cells (RAOEC) were pretreated with As-IV, SB203580 (p38 MAPK inhibitor) for 2 h prior to the addition of high glucose (33 mM glucose). Our findings indicated that As-IV improved impaired endothelium-dependent relaxation and increased the levels of endothelial NO synthase (eNOS) and nitric oxide (NO) both in vivo and in vitro. Besides, As-IV treatment inhibited the elevated inflammation and oxidative stress in diabetic model both in vivo and in vitro. Moreover, As-IV administration reversed the upregulated expression of P2X7R and p-p38 MAPK in vivo and in vitro. Additionally, the effects of both P2X7R siRNA and SB203580 on endothelial cells were similar to As-IV. Collectively, our study demonstrated that As-IV rescued endothelial dysfunction induced by high glucose via inhibition of P2X7R dependent p38 MAPK signaling pathway. This provides a theoretical basis for the further study of the vascular endothelial protective effects of As-IV.
Collapse
|
|
29
|
Suppression of Oxygen Radicals Protects Diabetic Endothelium Damage and Tissue Perfusion in a Streptozotocin-Induced Diabetes Rodent Model. Ann Plast Surg 2020; 82:S18-S22. [PMID: 30540602 DOI: 10.1097/sap.0000000000001723] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Oxygen free radicals play a central role in diabetic angiopathy. This study investigated whether suppression of oxygen radicals could decrease endothelial damage and increase peripheral tissue circulation in a diabetic rodent model. METHODS Sprague-Dawley rats were treated using streptozotocin to induce diabetes. The experiments were performed 4 weeks after diabetes induction: group 1: control, consisted of normal rats; group 2: diabetes, did not receive treatment; groups III (SOD10) and IV (SOD50): diabetes, received polyethylene glycol-conjugated superoxide dismutase (SOD), an antioxidant, 10 and 50 U/kg per day intraperitoneally for 4 weeks. Each subgroup consisted of 10 rats. Oxygen radicals in blood mononuclear cells were detected by flow cytometry. The blood lipid peroxidation byproduct malondialdehyde was measured. Tissue perfusion of hind limb was examined by laser Doppler. The expressions of oxygen radicals, as demonstrated by 8-hydroxyguanosine (8-OG), and constitutive endothelial nitric oxide synthase in distal femoral vessels were examined by immunohistochemical staining. RESULTS Oxygen radicals, as demonstrated by H2O2 with 2',7'-dichlorofluorescin diacetate-conjugated expression, were significantly increased in diabetic rats. However, the SOD treatment groups significantly suppressed the H2O2 reaction. Diabetic-induced high malondialdehyde levels were significantly suppressed in the SOD50 group. The topical tissue blood perfusion was significantly increased as detected by laser Doppler in SOD10 and SOD50 groups, as compared with that in diabetes without treatment group (P < 0.05). The expression of 8-OG was markedly increased in the diabetic endothelium and subintima compared with that in normal vessels. Polyethylene glycol-conjugated SOD significantly suppressed 8-OG expression and protected endothelial nitric oxide synthase expression. CONCLUSIONS Suppression of oxygen radicals, particularly with the higher dosage of polyethylene glycol-conjugated SOD at 50 U/kg per day, could have a positive effect to protect against endothelial damage and enhance peripheral perfusion in diabetes.
Collapse
|
|
30
|
Association between serum adropin levels and isolated coronary artery ectasia in patients with stable angina pectoris. Anatol J Cardiol 2020; 22:250-255. [PMID: 31674937 PMCID: PMC6955056 DOI: 10.14744/anatoljcardiol.2019.90349] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVE Dilation of one or more coronary artery segments to a diameter at least 1.5 times that of a normal adjacent segment is referred to as coronary artery ectasia (CAE). Adropin is a protein involved in endothelial function and is shown to have a protective effect on the regulation of cardiac functions. Atherosclerosis and endothelial dysfunction play an important role in the development of CAE. The aim of this study was to investigate the association between serum adropin levels and isolated CAE. METHODS Patients with stable angina pectoris who underwent coronary angiography (CAG) between August 2017 and July 2018 were evaluated prospectively. A total of 92 subjects were included in the study-40 patients over 18 years old and diagnosed with isolated CAE based on CAG findings and a control group of 52 patients. RESULTS Serum adropin level was found to be significantly lower in the isolated CAE group compared to the control group (1019.57 pg/mL and 1151.10 pg/mL, respectively, p=0.010). The isolated CAE group also exhibited a significantly higher mean platelet volume than that in the control group (10.75 fL and 10.17 fL, respectively, p=0.011). CONCLUSION Our results show that there is an association between low serum adropin level and isolated CAE.
Collapse
|
|
31
|
Phthalate exposure increased the risk of early renal impairment in Taiwanese without type 2 diabetes mellitus. Int J Hyg Environ Health 2020; 224:113414. [DOI: 10.1016/j.ijheh.2019.10.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 10/21/2019] [Accepted: 10/21/2019] [Indexed: 02/08/2023]
|
|
32
|
Pingali U, Nutalapati C, Illendulla VS. Evaluation of the Effect of Fish Oil Alone and in Combination with a Proprietary Chromium Complex on Endothelial Dysfunction, Systemic Inflammation and Lipid Profile in Type 2 Diabetes Mellitus - A Randomized, Double-Blind, Placebo-Controlled Clinical Study. Diabetes Metab Syndr Obes 2020; 13:31-42. [PMID: 32021349 PMCID: PMC6954851 DOI: 10.2147/dmso.s220046] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 12/07/2019] [Indexed: 12/11/2022] Open
Abstract
PURPOSE This study was conducted to evaluate the effectiveness of fish oil alone and with an adjunct, a proprietary chromium complex (PCC), on cardiovascular parameters - endothelial dysfunction, lipid profile, systemic inflammation and glycosylated hemoglobin - in a 12-week randomized, double-blind, placebo-controlled clinical study in type 2 diabetes mellitus subjects. PATIENTS AND METHODS In this randomized, double-blind, parallel group study, 59 subjects in three groups completed the study: Group A, fish oil 2000 mg; Group B, fish oil 2000 mg + PCC 10 mg (200 µg of Cr3+); and Group C, fish oil 2000 mg + PCC 20 mg (400 µg of Cr3+) daily for 12 weeks (2000 mg of fish oil contained 600 mg of eicosapentaenoic acid [EPA] and 400 mg of docosahexaenoic acid [DHA], the omega-3 fatty acids). Endothelial function, by estimating reflection index (RI), biomarkers of oxidative stress (nitric oxide [NO], malondialdehyde [MDA], glutathione [GSH]) and inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], endothelin-1) were evaluated at baseline, and 4 and 12 weeks. Lipid profile, platelet aggregation and glycosylated hemoglobin [HbA1c) were tested at baseline and 12 weeks. Any reported adverse drug reactions were recorded. Statistical analysis was performed using GraphPad Prism 8. RESULTS The present study shows that fish oil by itself, at a dose of 2000 mg (600 mg of EPA + 400 mg of DHA) per day, led to significant, but only modest, improvement in cardiovascular parameters (RI from -2.38±0.75 to -3.92±0.60, MDA from 3.77±0.16 to 3.74±0.16 nM/mL, NO from 30.60±3.18 to 32.12±3.40 µM/L, GSH from 568.93±5.91 to 583.95±6.53 µM/L; p≤0.0001), including triglyceride levels. However, when PCC was added to fish oil, especially at the 20 mg dose, there were highly significant improvements in all the parameters tested (RI from -2.04±0.79 to -8.73±1.36, MDA from 3.67±0.39 to 2.89±0.34 nM/mL, NO from 28.98±2.93 to 40.01±2.53 µM/L, GSH from 553.82±8.18 to 677.99±10.19 µM/L; p≤0.0001), including the lipid profile. It is noteworthy that the triglycerides were decreased significantly by addition of 20 mg of PCC although the dose of fish oil was only 2 g/day and the baseline triglyceride levels were only about 200 mg/dL. Fish oil alone did not significantly decrease the HbA1c, whereas the addition of 20 mg of PCC did. CONCLUSION Addition of PCC, especially at 20 mg dose, significantly improves the efficacy of fish oil in addressing cardiovascular risk factors compared to fish oil given alone.
Collapse
Affiliation(s)
- Usharani Pingali
- Department of Clinical Pharmacology & Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, 500082, India
- Correspondence: Usharani Pingali Department of Clinical Pharmacology & Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad500082, Telangana, IndiaTel +91 9849574143 Email
| | - Chandrasekhar Nutalapati
- Department of Clinical Pharmacology & Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, 500082, India
| | | |
Collapse
|
|
33
|
Wang AYM. Does Vitamin B 12 Delay CKD Progression? Am J Kidney Dis 2019; 75:317-319. [PMID: 31866227 DOI: 10.1053/j.ajkd.2019.10.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 10/18/2019] [Indexed: 11/11/2022]
Affiliation(s)
- Angela Yee-Moon Wang
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
| |
Collapse
|
|
34
|
Therapeutic and diagnostic potential of nanomaterials for enhanced biomedical applications. Colloids Surf B Biointerfaces 2019; 180:411-428. [DOI: 10.1016/j.colsurfb.2019.05.008] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 05/02/2019] [Accepted: 05/07/2019] [Indexed: 01/01/2023]
|
|
35
|
Hägg-Holmberg S, Dahlström EH, Forsblom CM, Harjutsalo V, Liebkind R, Putaala J, Tatlisumak T, Groop PH, Thorn LM. The role of blood pressure in risk of ischemic and hemorrhagic stroke in type 1 diabetes. Cardiovasc Diabetol 2019; 18:88. [PMID: 31288813 PMCID: PMC6617855 DOI: 10.1186/s12933-019-0891-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 06/25/2019] [Indexed: 12/23/2022] Open
Abstract
Background Hypertension is one of the strongest risk factors for stroke in the general population, while systolic blood pressure has been shown to independently increase the risk of stroke in type 1 diabetes. The aim of this study was to elucidate the association between different blood pressure variables and risk of stroke in type 1 diabetes, and to explore potential nonlinearity of this relationship. Methods We included 4105 individuals with type 1 diabetes without stroke at baseline, participating in the nationwide Finnish Diabetic Nephropathy Study. Mean age at baseline was 37.4 ± 11.9 years, median duration of diabetes 20.9 (interquartile range 11.5–30.4) years, and 52% were men. Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Based on these pulse pressure (PP) and mean arterial pressure (MAP) were calculated. Strokes were classified based on medical and autopsy records, as well as neuroimaging. Cox proportional hazard models were performed to study how the different blood pressure variables affected the risk of stroke and its subtypes. Results During median follow-up time of 11.9 (9.21–13.9) years, 202 (5%) individuals suffered an incident stroke; 145 (72%) were ischemic and 57 (28%) hemorrhagic. SBP, DBP, PP, and MAP all independently increased the risk of any stroke. SBP, PP, and MAP increased the risk of ischemic stroke, while SBP, DBP, and MAP increased the risk of hemorrhagic stroke. SBP was strongly associated with stroke with a hazard ratio of 1.20 (1.11–1.29)/10 mmHg. When variables were modeled using restricted cubic splines, the risk of stroke increased linearly for SBP, MAP, and PP, and non-linearly for DBP. Conclusions The different blood pressure variables are all independently associated with increased risk of stroke in individuals with type 1 diabetes. The risk of stroke, ischemic stroke, and hemorrhagic stroke increases linearly at blood pressure levels less than the current recommended treatment guidelines. Electronic supplementary material The online version of this article (10.1186/s12933-019-0891-4) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Stefanie Hägg-Holmberg
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.,Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Emma H Dahlström
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.,Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Carol M Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.,Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.,Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Ron Liebkind
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland
| | - Jukka Putaala
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland
| | - Turgut Tatlisumak
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland.,Department of Clinical Neuroscience/Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.,Department of Neurology, Sahlgrenska University Hospital, Göteborg, Sweden
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland. .,Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. .,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. .,Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
| | - Lena M Thorn
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.,Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
| | | |
Collapse
|
|
36
|
Jain A, Mehrotra V, Jha I, Jain A. In vivo studies demonstrate that endothelin-1 traps are a potential therapy for type I diabetes. J Diabetes Metab Disord 2019; 18:133-143. [PMID: 31275884 DOI: 10.1007/s40200-019-00400-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 03/14/2019] [Indexed: 12/15/2022]
Abstract
Background Type 1 diabetes is a serious, lifelong condition where the body's blood glucose level increases because of the body's inability to make insulin. An important consequence of this is the increased expression of extracellular matrix proteins, such as fibronectin and collagen 4α1, in key tissues and organs like the heart and kidneys. Diabetes is also associated with increased plasma levels of the vasoactive peptide endothelin (ET)-1. This further aggravates the expression of the ECM proteins. There are also important consequences of increased glucose and ET-1 levels in diabetes on the heart, termed diabetic cardiomyopathy. Methods We have previously reported the development of ET-traps, which potently and significantly reduce pathological levels of ET-1. In this study, we tested the in vivo therapeutic potential of ET-traps for type 1 diabetes using the B6 mouse model. Results Following subcutaneous administration of ET-traps 3 times a week, over a 2 month period, the 500 nM dose of ET-traps gave a significant reduction in collagen 4α1 expression in the heart and kidney, returning it back to control, non-diabetic levels at both the mRNA and protein levels. The expression of fibronectin mRNA is also returned to control levels with the 500 nM dose of ET-traps. The efficacy of ET-traps for type 1 diabetes was further evinced by immunohistochemistry data, echocardiography studies (measuring left ventricular systolic function and diastolic dysfunction) and a measure of urine creatinine and albumin levels. In all analyses, the 500 nM dose of ET-traps returns the different measures to control, non-diabetic levels. Conclusion Data from this study show that in a mouse model ET-traps have a potent and significant therapeutic effect on diabetes disease pathology. Future studies could further evaluate the use of ET-traps as a therapy for diabetes, including taking them through clinical trials.
Collapse
Affiliation(s)
- Arjun Jain
- 1Accelerate Cambridge, Judge Business School, University of Cambridge, Cambridge, UK
| | - Vidhi Mehrotra
- 1Accelerate Cambridge, Judge Business School, University of Cambridge, Cambridge, UK
| | - Ira Jha
- 2National University of Singapore, Singapore, Singapore
- 3Indian Institute of Management, Ahmedabad, India
| | - Ashok Jain
- 1Accelerate Cambridge, Judge Business School, University of Cambridge, Cambridge, UK
| |
Collapse
|
|
37
|
Sun W, Gao Y, Ding Y, Cao Y, Chen J, Lv G, Lu J, Yu B, Peng M, Xu H, Sun Y. Catalpol ameliorates advanced glycation end product-induced dysfunction of glomerular endothelial cells via regulating nitric oxide synthesis by inducible nitric oxide synthase and endothelial nitric oxide synthase. IUBMB Life 2019; 71:1268-1283. [PMID: 30861639 DOI: 10.1002/iub.2032] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 02/17/2019] [Indexed: 12/11/2022]
Abstract
Catalpol (Cat.) is an iridoid glucoside extracted from the root of Rehmannia glutinosa Libosch. In this study, we investigated whether Cat. could protect the mouse glomerular endothelial cells against the deleterious effect induced by advanced glycation end products (AGEs) and explored potential mechanisms. We found that 10 μM Cat. showed a protective effect on dead cells stimulated by AGEs. Cat. significantly decreased the expression of p-NF-κBp65 and inducible nitric oxide synthase (iNOS) and increased the expression of phosphorylated-endothelial nitric oxide synthase (p-eNOS; Ser1177), PI3K, p-Akt (Thr308), and total-Akt. Moreover, Cat. restored the integrity of glomerular endothelial barrier by increasing endothelial tight gap junction protein and ameliorated the endothelial hyperpermeability induced by AGEs via modulating the nitric oxide (NO) production. Additionally, Cat. attenuated the massive release of NO induced by AGEs, inhibiting the macrophage infiltration by modulating the NO production, accompanied by the decrease in the release of monocyte chemoattractant protein-1 and intercellular cell adhesion molecule-1 in vitro. Therefore, Cat. ameliorated AGEs-induced endothelial dysfunction via inhibiting the NF-κB/iNOS pathway and activating the PI3K/Akt/eNOS pathway. © 2019 IUBMB Life, 71(9):1268-1283, 2019.
Collapse
Affiliation(s)
- Weixiang Sun
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Department of Pharmacology, School of Pharmacy, Hanlin College, Nanjing University of Chinese Medicine, Taizhou, People's Republic of China
| | - Yuyan Gao
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Yushi Ding
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Ying Cao
- Department of Pharmacology, School of Pharmacy, Hanlin College, Nanjing University of Chinese Medicine, Taizhou, People's Republic of China
| | - Jing Chen
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Gaohong Lv
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Jinfu Lu
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Bin Yu
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Meilin Peng
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Huiqin Xu
- Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.,Department of Pharmacology, School of Pharmacy, Hanlin College, Nanjing University of Chinese Medicine, Taizhou, People's Republic of China
| | - Yun Sun
- Department of Pharmacology, School of Pharmacy, Hanlin College, Nanjing University of Chinese Medicine, Taizhou, People's Republic of China
| |
Collapse
|
|
38
|
Owuor OH, Chege P. CRYPTOCOCCAL meningitis in a HIV negative newly diagnosed diabetic patient: a CASE report. BMC Infect Dis 2019; 19:5. [PMID: 30606110 PMCID: PMC6318972 DOI: 10.1186/s12879-018-3625-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 12/17/2018] [Indexed: 12/28/2022] Open
Abstract
Background This case report emphasizes the need to recognize cryptococcus as a possible cause of meningitis in non-HIV patients in Sub-Saharan Africa and to highlight the possibility of grave outcomes due to the paradoxical immune response in diabetic patients with cryptococcus meningitis. It also highlights the need for widespread availability of amphotericin-B and flucytosine in hospitals in Sub-Saharan Africa. Case presentation A 27 year old African lady was admitted with generalized tonic clonic seizures lasting 5 to 10 min. These seizures were preceded by severe frontal headaches radiating to the occiput and neck and associated with chills, photophobia and loss of consciousness. She was tachycardic and had tongue bites on the lateral aspects of her tongue. Kernig’s and Brudzinski’s signs were positive. India ink was positive on two cerebrospinal fluid (CSF) samples. She had hyperglycemia and glucosuria as well. She was diagnosed with cryptococcal meningitis in diabetes and had a remarkable response to fluconazole monotherapy. She went home on maintenance dose of fluconazole having made full recovery. and is currently on prophylactic doses of fluconazole. Conclusions With the rising prevalence of diabetes in Sub-Saharan Africa, coupled with the low levels of adequate glucose control, cryptococcal meningitis should be considered in the differential diagnosis for diabetic patients presenting with chronic headache, fever and neurologic deficits.
Collapse
Affiliation(s)
- Odhiambo Henry Owuor
- School of Medicine, Department of Family Medicine, Moi University, P. O. Box, Eldoret, 3900-30100, Kenya.
| | - Patrick Chege
- School of Medicine, Department of Family Medicine, Moi University, P. O. Box, Eldoret, 3900-30100, Kenya
| |
Collapse
|
|
39
|
Puddu A, Sanguineti R, Maggi D, Nicolò M, Traverso CE, Cordera R, Viviani GL. Advanced Glycation End-Products and Hyperglycemia Increase Angiopoietin-2 Production by Impairing Angiopoietin-1-Tie-2 System. J Diabetes Res 2019; 2019:6198495. [PMID: 31828164 PMCID: PMC6881581 DOI: 10.1155/2019/6198495] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 10/11/2019] [Accepted: 10/18/2019] [Indexed: 12/19/2022] Open
Abstract
The angiopoietin-Tie-2 system plays a crucial role in the maintenance of endothelial integrity. Hyperglycemia and advanced glycation end-products (AGEs) are involved in endothelial cell dysfunction responsible of the pathogenesis of microvascular complications of diabetes. Here, we investigated whether glycated serum (GS) or hyperglycemia (HG) affect the angiopoietin-Tie-2 system in the microvascular endothelial cells HMEC-1. We found that culture for 5 days in the presence of AGEs and HG (alone or in combination) decreased cell proliferation, increased reactive oxygen species (ROS) production, and reduced ratio between the oxidized and the reduced form of glutathione. Since angiopoietin-1 (Ang-1) signaling regulates angiopoietin-2 (Ang-2) expression through inactivation of the forkhead transcription factor FoxO1, we investigated intracellular signaling of Ang-1 and expression of Ang-2. HG and AGEs reduced phosphorylation of Akt and abrogated phosphorylation of FoxO1 induced by Ang-1 without affecting neither Tie-2 expression nor its activation. Furthermore, AGEs and/or HG induced nuclear translocation of FoxO1 and increased Ang-2 production. In conclusion, we demonstrated that both hyperglycemia and AGEs affect the angiopoietin-Tie-2 system by impairing Ang-1/Tie-2 signaling and by increasing Ang-2 expression. These results suggest that therapeutic strategies useful in preventing or delaying the onset of diabetic vascular complications should be aimed to preserve Ang-1 signaling.
Collapse
Affiliation(s)
- Alessandra Puddu
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
| | - Roberta Sanguineti
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
| | - Davide Maggi
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
| | - Massimo Nicolò
- Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genova 16132, Italy
- Fondazione per la Macula Onlus, Genova 16132, Italy
| | - Carlo E. Traverso
- Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genova 16132, Italy
| | - Renzo Cordera
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
| | - Giorgio L. Viviani
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
| |
Collapse
|
|
40
|
Katsuta H, Tsuboi K, Yamamoto H, Goto H. Correlations Between Serum Cholesterol and Vascular Lesions in Fabry Disease Patients. Circ J 2018; 82:3058-3063. [PMID: 30282881 DOI: 10.1253/circj.cj-18-0378] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Fabry disease is an X-linked lysosomal storage disorder and shows globotriosylceramide (Gb3) accumulation in multiple organs, resulting from a deficiency of α-galactosidase. In patients with Fabry disease, cardiovascular disease occurs at an early age. Previous studies have shown that serum levels of high-density lipoprotein-cholesterol (HDL-C) increase in this disease, yet its clinical significance for cardiovascular disease remains unclear. METHODS AND RESULTS In order to determine why the serum HDL-cholesterol is high in various cardiovascular diseases of Fabry disease patients, we evaluated the serum lipid profiles, ocular vascular lesions, and levels of serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 in 69 patients with Fabry disease diagnosed by genetic examination. The serum HDL-C/total cholesterol (T-Chol) ratio was significantly high, especially in male patients (41.5±1.7%) regardless of body mass index. Ocular vascular lesions were more likely to occur in female patients with a high HDL-C/T-Chol ratio compared with most male patients. Female patients with a high HDL-C/T-Chol ratio also presented a high serum VEGF level, suggesting that vascular endothelium dysfunction and arteriosclerotic changes progress more severely than in patients with a normal HDL-C/T-Chol ratio. In most patients, enzyme replacement therapy improved serum Gb3 and lyso-Gb3 levels, but these Gb3 and lyso-Gb3 still remained higher than in healthy controls, which appears to result in continuous vascular arteriosclerotic changes. CONCLUSIONS We concluded that increased low-density lipoprotein-cholesterol uptake to the vascular wall caused by endothelial dysfunction is likely to contribute to the high HDL-C/T-Chol ratio observed in Fabry disease patients.
Collapse
|
|
41
|
Endothelin-1 traps potently reduce pathologic markers back to basal levels in an in vitro model of diabetes. J Diabetes Metab Disord 2018; 17:189-195. [PMID: 30918854 DOI: 10.1007/s40200-018-0360-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 10/01/2018] [Indexed: 12/12/2022]
Abstract
Background Diabetes mellitus is a group of metabolic disorders in which there are high blood glucose levels over a prolonged period. Diabetes is one of many diseases associated with pathologically elevated levels of endothelin (ET)-1. We have recently proposed the development of ET-traps, which are an antibody - based fusion protein that potently bind and sequester pathologically elevated levels of endothelin-1. Methods We constructed ET-traps that were found to be very potent binders to ET-1, with a KD of 32.5ρM. We then treated human retinal microvascular endothelial cells (HRMECs), which are an in vitro model of glucose induced cellular damage, with 10 nM ET-1 or high glucose levels (25 mM). Results In this study, we investigated the effects of our ET-trap constructs on the expression levels of both collagen 4α1 and fibronectin, which are both important pathologic markers in diabetes. Treating HRMECs with 10 nM ET-1 or 25 mM glucose significantly induces the expression of the ECM proteins fibronectin and collagen 4α1, as is found in chronic diabetic complications; Incubation of the cells with the ET-traps significantly prevented the increased expression of fibronectin and collagen 4α1 back to basal levels. This was found with both mRNA and protein expression levels of the two ECM proteins. Conclusion Our results provide the first evidence of the efficacy of ET-traps in reducing pathologic markers in an in vitro model (of diabetes). Further research is warranted to determine the efficacy of ET-traps as a therapeutic tool for diabetes, which is a major public health burden around the world.
Collapse
|
|
42
|
Dai Y, Lu H, Wang S, Chang S, Li C, Huang Z, Zhang F, Yang H, Shen Y, Chen Z, Qian J, Ge J. MicroRNA-216b actively modulates diabetic angiopathy through inverse regulation on FZD5. Gene 2018; 658:129-135. [PMID: 29477872 DOI: 10.1016/j.gene.2018.02.050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 02/14/2018] [Accepted: 02/21/2018] [Indexed: 12/01/2022]
Abstract
BACKGROUND In this work, we examined the angiogenic function of microRNA-216b in an in vitro rat diabetic model of myocardial microvascular endothelial cells (MMECs). METHODS MMECs were extracted from Wistar rats (MMEC(WI)) or diabetic Goto-Kakizaki (GK) rats (MMEC(GK)) and cultured in vitro. QRT-PCR was applied to compare miR-216b between MMEC(WI) and MMEC(GK). MiR-216b was downregulated in MMEC(GK). Its effects on angiogenic development, including invasion and proliferation, were evaluated. In MMEC(GK), putative miR-216b downstream target gene, frizzled class receptor 5 (FZD5), was evaluated by dual-luciferase reporter, qRT-PCR and western blot assays, respectively. FZD5 was further downregulated in MMEC(GK) with stable miR-216b downregulation to evaluate its functional role in regulating diabetic angiogenesis. RESULTS MiR-216b was markedly overexpressed in MMEC(GK). MiR-216b downregulation significantly enhanced angiogenesis in MMEC(GK) by promoting invasion and proliferation. FZD5 was inversely upregulated in miR-216b-downregulated MMEC(GK). Subsequently, FZD5 downregulation suppressed angiogenic development, by inhibiting invasion and proliferation in miR-216b-downregulated MMEC(GK). CONCLUSION MicroRNA-216b was overexposed in diabetic MMECs and its downregulation may actively enhance angiogenesis in diabetic angiopathy through inverse regulation on FZD5.
Collapse
Affiliation(s)
- Yuxiang Dai
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Hao Lu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Shen Wang
- Department of Cardiology, Xinhua Hospital of Zhejiang Province, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, China
| | - Shufu Chang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Chenguang Li
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zheyong Huang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Feng Zhang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Hongbo Yang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yi Shen
- Department of Geratology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhangwei Chen
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Juying Qian
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Junbo Ge
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| |
Collapse
|
|
43
|
Abstract
In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications.
Collapse
|
|
44
|
Li Y, Liang M, Wang G, Wang B, He M, Tang G, Yin D, Xu X, Huo Y, Cui Y, Hou FF, Qin X. Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients. Hypertension 2017; 70:300-306. [PMID: 28607125 DOI: 10.1161/hypertensionaha.117.09404] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 04/01/2017] [Accepted: 05/12/2017] [Indexed: 12/14/2022]
Abstract
We aimed to test the hypothesis that treatment with enalapril and folic acid is more effective in preventing new-onset proteinuria than enalapril alone among hypertensive patients. This is a post hoc analysis of the renal substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 13 071 eligible participants without proteinuria were randomized to receive a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n=6511) or 10-mg enalapril alone (n=6560). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. Secondary outcomes included a composite of the primary outcome and all-cause death and the annual rate of estimated glomerular filtration rate decline. After a median 4.4 years of treatment, the primary event occurred in 213 (3.9%) and 188 (3.5%) participants, respectively, in the enalapril and the enalapril–folic acid group (odds ratio, 0.90; 95% confidence interval, 0.74–1.11). However, among participants with diabetes mellitus at baseline, folic acid therapy resulted in a significant reduction in the risk for the primary event (3.7% in the enalapril–folic acid group versus 7.4% in the enalapril group; odds ratio, 0.48; 95% confidence interval, 0.29–0.81) and the composite event (odds ratio, 0.62; 95% confidence interval, 0.42–0.92) and a 55% slower annual rate of estimated glomerular filtration rate decline (0.5% versus 1.1% per year;
P
=0.002). Among those without diabetes mellitus at baseline, there were no between-group differences in all the outcomes. In conclusion, enalapril–folic acid therapy, compared with enalapril alone, significantly reduced the development of proteinuria in diabetic patients with hypertension.
Clinical Trial Registration—
URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT00794885.
Collapse
Affiliation(s)
- Youbao Li
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Min Liang
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Guobao Wang
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Binyan Wang
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Mingli He
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Genfu Tang
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Delu Yin
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Xin Xu
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Yong Huo
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Yimin Cui
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Fan Fan Hou
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| | - Xianhui Qin
- From the Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, China (Y.L., M.L., G.W., B.W., X.X., F.F.H., X.Q.); Department of Neurology, First People’s Hospital, Lianyungang, China (M.H.); Institute for Biomedicine (G.T.) and Department of Health Administration,
| |
Collapse
|
|
45
|
Stoyneva Z, Velcheva I, Antonova N, Titianova E. Microvascular reactivity to thermal stimulation in patients with diabetes mellitus and polyneuropathy. Clin Hemorheol Microcirc 2017; 65:67-75. [DOI: 10.3233/ch-15107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Z. Stoyneva
- Department of Neurology, University Hospital St. Ivan Rilsky – Sofia, Medical Universities of Sofia and Plovdiv, Bulgaria
| | - I. Velcheva
- Department of Neurology, University Hospital of Neurology and Psychiatry, Medical University, Sofia, Bulgaria
| | - N. Antonova
- Department of Biomechanics, Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - E. Titianova
- Clinic of Functional Diagnostics of the Nervous System, Military Medical Academy, Sofia, Bulgaria
| |
Collapse
|
|
46
|
Du LL, Fu QY, Xiang LP, Zheng XQ, Lu JL, Ye JH, Li QS, Polito CA, Liang YR. Tea Polysaccharides and Their Bioactivities. Molecules 2016; 21:E1449. [PMID: 27809221 PMCID: PMC6274327 DOI: 10.3390/molecules21111449] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 10/27/2016] [Accepted: 10/28/2016] [Indexed: 01/17/2023] Open
Abstract
Tea (Camellia sinensis) is a beverage beneficial to health and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of heteropolysaccharides bound with proteins. There is evidence showing that TPS not only improves immunity but also has various bioactivities, such as antioxidant, antitumor, antihyperglycemia, and anti-inflammation. However, inconsistent results concerning chemical composition and bioactivity of TPS have been published in recent years. The advances in chemical composition and bioactivities of TPS are reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS are also discussed.
Collapse
Affiliation(s)
- Ling-Ling Du
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
- National Tea and Tea product Quality Supervision and Inspection Center (Guizhou), Zunyi 563100, China.
| | - Qiu-Yue Fu
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Li-Ping Xiang
- National Tea and Tea product Quality Supervision and Inspection Center (Guizhou), Zunyi 563100, China.
| | - Xin-Qiang Zheng
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Jian-Liang Lu
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Jian-Hui Ye
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Qing-Sheng Li
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Curt Anthony Polito
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| | - Yue-Rong Liang
- Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China.
| |
Collapse
|
|
47
|
Hoffman RP, Dye AS, Huang H, Bauer JA. Glycemic variability predicts inflammation in adolescents with type 1 diabetes. J Pediatr Endocrinol Metab 2016; 29:1129-1133. [PMID: 27658133 PMCID: PMC5546213 DOI: 10.1515/jpem-2016-0139] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 08/01/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities. METHODS This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A1c (HbA1c), and HbA1c×duration area under the curve (A1cDur). RESULTS Seventeen adolescents (8 F/9M; age, 13.1±1.6 years (mean±SD); duration, 4.8±3.8 years, BMI, 20.3±3.1 kg/m2; A1c, 8.3±1.2%) were studied. Log CRP but was not related to age, duration, body mass index (BMI), HbA1c, or A1cDUR. TAOC increased as logA1cDUR increased (n=13, r=0.61, p=0.028). CRP and sICAM were not related to CGM average glucose but log CRP increased as 3 day glucose standard deviation increased (r=0.66, p=0.006). TAOC increased as glucose standard deviation increased (r=0.63, p=0.028). CONCLUSIONS Increased glucose variability is associated with increased inflammation in adolescents withT1D. Increased TAOC with increasing variability may be an effort to compensate for the ongoing oxidative stress.
Collapse
Affiliation(s)
| | - Amanda S. Dye
- Department of Pediatrics, West Virginia University, Charleston, WV, USA
| | - Hong Huang
- Department of Pediatrics, University of Kentucky, UK Medical Center MN, Lexington, KY, USA
| | - John A. Bauer
- Department of Pediatrics, University of Kentucky, UK Medical Center MN, Lexington, KY, USA
| |
Collapse
|
|
48
|
Nicolaides E, Jones CJ. Review: Type 2 diabetes — implications for macrovascular mechanics and disease. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/14746514020020011101] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Before macrovascular disease is established, type 2 diabetes is associated with structural and functional changes in large arteries that lead to increased stiffness, abnormal pulse wave travel and systolic hypertension. Structural changes result mainly from glycation of wall components. Functional changes originate in endothelial dysfunction. Increased arterial stiffness, or decreased arterial distensibility, increases pulse wave velocity and the amplitude of reflected waves, so that reflected waves arrive early and augment central systolic pressure. This promotes the development of left ventricular hypertrophy, an independent risk factor for cardiovascular mortality. One of the major mechanisms of arterial stiffening is endothelial dysfunction with reduced nitric oxide (NO)-mediated vasodilatation, the initial lesion in pre-atherosclerotic diabetes. To understand better the mechanisms of endothelial dysfunction will be vital if future therapeutic interventions are targeted to disease prevention. Protein glycation in poorly controlled diabetes is also damaging to blood vessels and must be limited by good diabetic control over the longer term.
Collapse
Affiliation(s)
| | - Christopher Jh Jones
- Welsh Heart Research Institute, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW,
| |
Collapse
|
|
49
|
Wotherspoon F, Laight DW, Shaw KM, Cummings MH. Review: Homocysteine, endothelial dysfunction and oxidative stress in type 1 diabetes mellitus. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/14746514030030050401] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Type 1 diabetes is associated with an increased risk of cardiovascular disease, which cannot be fully explained by traditional risk factors. Elevated plasma homocysteine is an independent risk factor for macrovascular disease in the general population. This review examines the evidence for hyperhomocysteinaemia in patients with type 1 diabetes and describes the mechanisms that may lead to increased macrovascular susceptibility. While reports of plasma homocysteine levels in type 1 diabetes are inconsistent, increased plasma homocysteine levels have been found in subgroups of patients with microalbuminuria, nephropathy and macrovascular disease. Although a direct causal relationship between plasma homocysteine and atherosclerosis remains to be proven, potential mechanisms of vascular damage by homocysteine include endothelial dysfunction linked to increased oxidative stress. This could contribute to the association between hyperhomocysteinaemia and macrovascular disease in type 1 diabetes.
Collapse
Affiliation(s)
- Fiona Wotherspoon
- Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Southwick Park Road, Cosham, Portsmouth, PO6 3LY, UK,
| | - David W Laight
- School of Pharmacy and Biomedical Studies, University of Portsmouth, St. Michaels Building, White Swan Road, Portsmouth, PO1 2DT, UK
| | - Kenneth M Shaw
- Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Southwick Park Road, Cosham, Portsmouth, PO6 3LY, UK
| | - Michael H Cummings
- Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Southwick Park Road, Cosham, Portsmouth, PO6 3LY, UK
| |
Collapse
|
|
50
|
Browne D, Meeking D, Shaw K, Cummings M. Review: Endothelial dysfunction and pre-symptomatic atherosclerosis in type 1 diabetes — pathogenesis and identification. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/14746514030030010401] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The vascular endothelium offers an attractive model for detecting functional abnormalities prior to structural changes in the vasculature. Demonstration of progression from endothelial dysfunction through to atherosclerosis is required. Measurements of forearm bloodflow, biochemical markers and biophysical assessments of the endothelium have been employed as research tools for investigating pre-symptomatic atherosclerosis. However, studies examining endothelial function in type 1 diabetes have been sparse and conflicting. Differences in methodology and the study populations were potential confounding factors. Augmented vasodilatory prostanoids compensate for reduced nitric oxide bioavailability in determining endothelial function in type 1 diabetes. Hyperglycaemia appears to be the initiating event in type 1 diabetes which promotes a variety of biochemical events which are pathogenic to the endothelium. Improved understanding of the endothelium may facilitate the development of novel diagnostic tools and interventions targeting the accelerated atherosclerosis associated with type 1 diabetes.
Collapse
Affiliation(s)
- Duncan Browne
- Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Cosham, Portsmouth, PO6 3LY, UK,
| | | | | | | |
Collapse
|