scholarly journals Animal models of diabetes-associated vascular diseases: An update on available models and experimental analysis

2020 ◽  
Author(s):  
Judy Choi ◽  
Judy de Haan ◽  
Arpeeta Sharma
Keyword(s):  
Animal Models ◽  
Experimental Analysis ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Vascular Diseases ◽  
Therapeutic Interventions ◽  
Molecular Pathways ◽  
Mortality And Morbidity ◽  
Diabetic Vascular Complications ◽  
Artery Disease

Diabetes is a chronic metabolic disorder associated with the accelerated development of macrovascular (atherosclerosis, coronary artery disease) and microvascular complications (nephropathy, retinopathy and neuropathy), which remain the principal cause of mortality and morbidity in this population. Current understanding of cellular and molecular pathways of diabetes-driven vascular complications as well as therapeutic interventions have arisen from studying disease pathogenesis in animal models. Diabetes-associated vascular complications are multi-faceted, involving the interaction between various cellular and molecular pathways. Thus, the choice of an appropriate animal model to study vascular pathogenesis is important in our quest to identify innovative and mechanism-based targeted therapies to reduce the burden of diabetic complications. Herein, we provide up-to-date information on available mouse models of both Type 1 and Type 2 diabetic vascular complications as well as experimental analysis and research outputs.

scholarly journals Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Akira Mima
Keyword(s):  
Microvascular Complications ◽  
Vascular Complications ◽  
Polyol Pathway ◽  
Therapeutic Interventions ◽  
Mortality And Morbidity ◽  
Dipeptidyl Peptidase 4 ◽  
Diabetic Vascular Complications ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Artery Disease

Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular and　microvascular complications. Macrovascular complications include coronary artery disease　and cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications.

Macrovascular Disease in Diabetes: Is the Mouse a Suitable Model?

2012 ◽  
Vol 120 (04) ◽  
pp. 194-196 ◽  
Author(s):  
O. Müller ◽  
H. Katus ◽  
J. Backs
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Knockout Mice ◽  
Vascular Complications ◽  
Macrovascular Disease ◽  
Suitable Model ◽  
Diabetic Mice ◽  
Advantages And Disadvantages ◽  
Diabetic Vascular Complications

AbstractTo elucidate the pathogenesis of macrovascular disease in diabetes, animal models are widely used. Diabetic mice are of particular interest because they can be crossed to knockout mice lacking specific genes that are under consideration to contribute to diabetic vascular complications. However, the mouse is relative resistant to develop atherosclerosis. Therefore, we review some commonly used mouse models and discuss their advantages and disadvantages.

scholarly journals Glycemic Variability and Vascular Complications in Patients with Type 2 Diabetes Mellitus

Folia Medica ◽  
2017 ◽  
Vol 59 (3) ◽  
pp. 270-278 ◽  
Author(s):  
Martin Caprnda ◽  
Dasa Mesarosova ◽  
Pablo Fabuel Ortega ◽  
Boris Krahulec ◽  
Emmanuel Egom ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Glycemic Variability ◽  
Cerebral Stroke ◽  
Chronic Hyperglycemia ◽  
Type 2 Dm ◽  
Artery Disease ◽  
Index Value

AbstractBackground:Presence of macro- and microvascular complications in patients with diabetes mellitus (DM) is not only related to chronic hyperglycemia represented by glycated hemoglobin (HbA1c) but also to acute glycemic fluctuations (glycemic variability, GV). The association between GV and DM complications is not completely clear. Aim of our study was to evaluate GV by MAGE index in patients with type 2 DM and to verify association of MAGE index with presence of macro- and microvascular DM complications.Methods:99 patients with type 2 DM were included in the study. Every patient had done big glycemic profile, from which MAGE index was calculated. Anthropometric measurements, evaluation of HbA1c and fasting plasma glucose (FPG) and assessment for macrovascular (coronary artery disease – CAD; peripheral artery disease – PAD; cerebral stroke – CS) and microvascular (diabetic retinopathy – DR; nephropathy – DN; peripheral neuropathy – DPPN) DM complications were done.Results:Average MAGE index value was 5.15 ± 2.88 mmol/l. We found no significant differences in MAGE index values in subgroups according to presence of neither CAD, CS, PAD nor DR, DN, DPPN. MAGE index value significantly positively correlated with FPG (p < 0.01) and HbA1c (p < 0.001) and negatively with weight (p < 0.05).Conclusion:In our study we failed to show association of MAGE index with presence of macrovascular and microvascular complications in patients with type 2 DM. However, this negative result does not necessarily disprove importance of glycemic variability in pathogenesis of diabetic complications.

scholarly journals Post PCI Vascular and Bleeding Complications in Patients with or Without CKD

2016 ◽  
Vol 01 (01) ◽  
pp. 022-027
Author(s):  
Harish Oruganti ◽  
Jyotsna Maddury
Keyword(s):  
Renal Failure ◽  
Kidney Diseases ◽  
Vascular Complications ◽  
Therapeutic Interventions ◽  
Bleeding Complications ◽  
Access Site ◽  
Chronic Kidney Diseases ◽  
Artery Disease ◽  
General Populations ◽  
Distal Embolisation

AbstractBACKGROUND: There is increasing trend of both Cardiovascular disease (CVD) and chronic kidney diseases (CKD) in general populations. The individuals with CKD are more likely to die of CVD than of kidney failure. Both diagnostic and therapeutic interventions are crucial in management of CKD patients with coronary artery disease. As CKD itself is associated with more bleeding complications we aim to study the incidence of vascular complications (vessel thrombosis, distal embolisation, dissection, poorly controlled bleeding at puncture site, pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, and development of femoral neuropathy) in Percutaneous intervention (PCI) patients with renal failure.METHODS: 950 patients who underwent PCI procedures were classified into CKD (GFR<60ml/min/m2) (n=380, 40%) and non-CKD (n=570, 60%) groups. Two groups were analyzed for the occurrence of vascular complications post PCI.RESULTS: Vascular complications were seen in 28 out of 380 patients with CKD (7.37%) and 17 out of 570 patients without CKD (2.98%). Patients with renal failure (GFR<60ml/min/m2) were found to have higher risk of vascular complications post PCI. [p = 0.03, OR = 2.588 (1.344-5.017)]. Non access site complications were more common in patients with CKD compared to non CKD. 16 patients with CKD developed non access site complications compared to 9 in patients without CKD.[p=0.001, odds ratio 2.793(1.15-6.916)CONCLUSIONS: This study demonstrates higher risk of vascular complications post-PCI in patients with CKD compared to non CKD patients. Higher incidence of non access site complications was also observed in CKD patients.

scholarly journals Mini-review: diabetic renal complications, a potential stinky remedy

2016 ◽  
Vol 310 (2) ◽  
pp. F119-F122 ◽  
Author(s):  
Utpal Sen ◽  
Sathnur Pushpakumar
Keyword(s):  
Therapeutic Potential ◽  
Vascular Complications ◽  
Vital Role ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Number Of Patients ◽  
Matrix Metabolism ◽  
Artery Disease ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in diabetic patients. Despite optimal management, a significant number of patients progress toward end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini-review highlights the recent findings on the role of H2S in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow-releasing H2S compounds and its therapeutic potential is also included.

scholarly journals Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications

2021 ◽  
Vol 12 ◽  
Author(s):  
Vinay Singh Tanwar ◽  
Marpadga A. Reddy ◽  
Rama Natarajan
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Protein Coding ◽  
Altered Expression ◽  
Diabetic Vascular Complications ◽  
Obesity And Diabetes ◽  
Non Coding Rnas ◽  
Species Specific

Chronic metabolic disorders such as obesity and diabetes are associated with accelerated rates of macrovascular and microvascular complications, which are leading causes of morbidity and mortality worldwide. Further understanding of the underlying molecular mechanisms can aid in the development of novel drug targets and therapies to manage these disorders more effectively. Long non-coding RNAs (lncRNAs) that do not have protein-coding potential are expressed in a tissue- and species-specific manner and regulate diverse biological processes. LncRNAs regulate gene expression in cis or in trans through various mechanisms, including interaction with chromatin-modifying proteins and other regulatory proteins and via posttranscriptional mechanisms, including acting as microRNA sponges or as host genes of microRNAs. Emerging evidence suggests that major pathological factors associated with diabetes such as high glucose, free fatty acids, proinflammatory cytokines, and growth factors can dysregulate lncRNAs in inflammatory, cardiac, vascular, and renal cells leading to altered expression of key inflammatory genes and fibrotic genes associated with diabetic vascular complications. Here we review recent reports on lncRNA characterization, functions, and mechanisms of action in diabetic vascular complications and translational approaches to target them. These advances can provide new insights into the lncRNA-dependent actions and mechanisms underlying diabetic vascular complications and uncover novel lncRNA-based biomarkers and therapies to reduce disease burden and mortality.

scholarly journals An analytical study of the prevalence and prescribed pattern vascular complication for type II diabetic patient in Indian tertiary care hospitals

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 310-314
Author(s):  
Satya Preethi ◽  
Beeraka Chandra Sekhar ◽  
Pandiyan K R ◽  
Rajkumar R
Keyword(s):  
Glycemic Control ◽  
Lifestyle Modification ◽  
Patient Adherence ◽  
Microvascular Complications ◽  
Tertiary Care ◽  
Blood Glucose Control ◽  
Vascular Complications ◽  
Vascular Complication ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications

Diabetes mellitus (DM) is a common metabolic disorder. It is associated with complications which will affect the quality of life. Failure to control elevated blood sugar or inadequate treatment of diabetes could cause many complications.  A prospective observational study is used to assess the prevalence of diabetic vascular complications in 105 types of II diabetic patients. A date was collected regarding patient's demographic and clinical characteristics. Based on our study criteria, males were more when compared to females in getting vascular complications & also. Complications were more prominent in the age group of 50-65years. Of all microvascular complications, Nephropathy was major, whereas, in macro-vascular complications, CAD was prominent. Poor glycemic control and a long length of ailment appear to be the most significant danger factors for these complexities. Doctors assume a significant function to endorse hostile to diabetic meds and Pharmacist plays a sharp task to assess the medicine design so as to accomplish fruitful treatment. The currently anti-diabetic drugs are effective, but a lot of factors such as patient adherence, education related to diabetes, lifestyle modification, cost and type of medication have an association with glycemic control. The commonly prescribed anti-diabetic drug was Insulin. Metformin was the most preferred drug both as monotherapy and combination therapy.  Although polypharmacy was observed, drug utilization pattern can be rational owing to a higher prevalence of complications. Minimization of the occurrence of complications should be courage by early diagnosis, intensive blood glucose control and rational drug selections.

scholarly journals Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications

2019 ◽  
Vol 20 (15) ◽  
pp. 3737 ◽  
Author(s):  
Kenichi Goto ◽  
Takanari Kitazono
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Current Knowledge ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Muscle Cells ◽  
Diabetes In Animals ◽  
Diabetic Vascular Complications

Diabetes mellitus is one of the major risk factors for cardiovascular disease and is an important health issue worldwide. Long-term diabetes causes endothelial dysfunction, which in turn leads to diabetic vascular complications. Endothelium-derived nitric oxide is a major vasodilator in large-size vessels, and the hyperpolarization of vascular smooth muscle cells mediated by the endothelium plays a central role in agonist-mediated and flow-mediated vasodilation in resistance-size vessels. Although the mechanisms underlying diabetic vascular complications are multifactorial and complex, impairment of endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells would contribute at least partly to the initiation and progression of microvascular complications of diabetes. In this review, we present the current knowledge about the pathophysiology and underlying mechanisms of impaired EDH in diabetes in animals and humans. We also discuss potential therapeutic approaches aimed at the prevention and restoration of EDH in diabetes.

scholarly journals The effect of guideline revisions on vascular complications of type 2 diabetes

2019 ◽  
Vol 10 ◽  
pp. 204201881987540 ◽  
Author(s):  
Ralph Heijmans ◽  
Sunny S. Singh ◽  
Aloysius G. Lieverse ◽  
Eric J.G. Sijbrands ◽  
Mandy van Hoek
Keyword(s):  
Type 2 Diabetes ◽  
Diabetes Care ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Continuous Variable ◽  
Diabetes Mellitus Type Ii ◽  
Logistic Regression Models ◽  
Artery Disease ◽  
The Impact

Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend < 0.001). Conclusions: The introduction of the first diabetes guideline and subsequent revisions have reduced the risk of macrovascular and microvascular complications of type 2 diabetes, most strongly in diabetic retinopathy. This indicates that real-time diabetes care has improved over time.

The Role of Protein Kinase C Activation in the Pathogenesis of Diabetic Vascular Complications

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 222-227 ◽  
Author(s):  
Joong Yeol Park ◽  
Sung-Woo Ha ◽  
George L. King
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
De Novo ◽  
Vascular Complications ◽  
Vascular Diseases ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Kinase C

Many vascular diseases in diabetes are known to be associated with the activation of the diacylglycerol (OAG)protein kinase C (PKC) pathway. The major source of OAG that is elevated in diabetes is de novo synthesis from glycolytic intermediates. Among the various PKC isoforms, the β-isoform has been shown to be persistently activated in diabetic animals. Multiple lines of evidence have shown that many vascular alterations in diabetes such as a decrease in the activity of Na+-K+ -adenosine triphosphatase (Na+-K+-ATPase), and increases in extracellular matrix, cytokines, permeability, contractility, and cell proliferation -are caused by activation of PKC. Inhibition of PKC by two different kinds of PKC inhibitors, LY333531, a selective PKC-β-isoform inhibitor, and d-α-tocopherol, were able to prevent or reverse the various vascular dysfunctions in diabetic rats. These results have also provided in vivo evidence that OAG-PKC activation could be responsible for the hyperglycemia-induced vascular dysfunctions in diabetes. Clinical studies are now being performed to clarify the pathogenic roles of the OAG-PKC pathway in developing vascular complications in diabetic patients.

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