scholarly journals Diabetes Microvascular Complications: An Overview of Epigenetic Modifications

2020 ◽  
Author(s):  
Neerja Aggarwal ◽  
Pawan Kumar Kare
Keyword(s):  
Association Studies ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Polyol Pathway ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Diabetic Vascular Complications ◽  
Current Scenario ◽  
History Of ◽  
Diabetic Microvascular Complications

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are two serious and long-standing microvascular complications of type 2 diabetes mellitus (T2DM) whose burden is increasing worldwide due to increasing burden of T2DM. Several factors which may predispose to the development of DN and DR are persistent hyperglycemia and its consequences such as formation of advanced glycation end products (AGEs), activation of hexosamine pathway, polyol pathway, uncontrolled blood pressure, increased oxidative stress, age, family history of kidney disease or hypertension, ethnic background etc. However, the pathophysiological mechanisms of these complications are complicated and not completely understood yet. Hence it is the demand to discover newer approaches to treat these devastating complications completely. Recently, various epigenetic modifications, which are the transmissible alterations in the expressions of a gene, are being studied to understand the pathophysiology of diabetic vascular complications. Metabolic and environmental factors may lead to dysregulated epigenetic mechanisms which might further affect the chromatin structure and related expressions of a gene, which may lead to diabetes-associated complications. Therefore, it is the need to explore its role in vascular complications in the current scenario. In this chapter, various epigenetic studies with regard to DN and DR, epigenome-wide association studies (EWAS) approach, and starting clinical material for such studies have been discussed. We have also summarized the better understanding of epigenetic alterations and their role in microvascular complications of diabetes through this chapter. The better understanding of epigenetic mechanisms and their role in diabetic microvascular complications could be used in clinical management of DN as well as DR or could be helpful to improve the available therapies for these complications.

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.

New Insights into Hyperglycemia-induced Molecular Changes in Microvascular Cells

2009 ◽  
Vol 89 (2) ◽  
pp. 116-127 ◽  
Author(s):  
S. Roy ◽  
K. Trudeau ◽  
S. Roy ◽  
Y. Behl ◽  
S. Dhar ◽  
...  
Keyword(s):  
Microvascular Complications ◽  
Vascular Complications ◽  
Diabetic Microangiopathy ◽  
Molecular Changes ◽  
Biochemical Alterations ◽  
Diabetic Vascular Complications ◽  
Basement Membrane Thickening ◽  
Microvascular Cells ◽  
Diabetic Microvascular Complications ◽  
Inflammation Cytokines

Hyperglycemia is the most prevalent characteristic of diabetes and plays a central role in mediating adverse effects on vascular cells during the progression of diabetic vascular complications. In diabetic microangiopathy, hyperglycemia induces biochemical and molecular changes in microvascular cells that ultimately progress to retinal, renal, and neural complications and extends to other complications, including advanced periodontal disease. In this review, we describe changes involving basement membrane thickening, tissue remodeling, gap junctions, inflammation, cytokines, and transcription factors, and their effects on the pathogenesis of diabetic microvascular complications. The majority of the changes described relate to retinal microangiopathy, since ultrastructural, structural, and biochemical alterations have been well-characterized in this tissue.

Mean Platelet Volume and Platelet Distribution Width Correlate with Microvascular Complications in Egyptian People with Type 2 Diabetes Mellitus

2021 ◽  
Vol 17 ◽  
Author(s):  
Mohammed I. Abd El-Ghany ◽  
Nahed Abdallah ◽  
Waleed Eldars
Keyword(s):  
Type 2 Diabetes ◽  
Mean Platelet Volume ◽  
Microvascular Complications ◽  
Fasting Blood Glucose ◽  
Vascular Complications ◽  
Platelet Distribution Width ◽  
Platelet Volume ◽  
Distribution Width ◽  
Diabetic Microvascular Complications

Background: Type 2 diabetes is a part of metabolic syndrome associated with a higher risk of vascular complications. Diabetes is characterized by changes in platelet morphology, function, and platelet hyperactivity so, it's considered a prothrombotic condition. Morbidity and mortality in people with type 2 diabetes-related to micro and macrovascular complications. Novel biomarkers are needed to identify and treat people at higher risk. Objective: The main objective of this controlled cross-sectional study was to evaluate Platelet volume indices (PVI) in subjects with type 2 diabetes with and without complications in comparison to subjects without diabetes. Methods: Hundred and thirty-five subjects aged from 35 to 60 years were subdivided into 3 groups. Group A includes 55 subjects with type 2 diabetes with complications. Group B includes 45 subjects with type 2 diabetes without complications. Group C includes 35 normal healthy subjects. Detailed clinical history was taken. Also, PVI, fasting blood glucose (FBG), hemoglobin A1c, and creatinine were obtained. Results: Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Plateletcrit (PCT), and Platelet large cell ratio (P-LCR) were significantly higher among subjects with retinopathy, nephropathy, and neuropathy than other subjects with diabetes who didn't develop complications (P<0.001). At cutoff value > 11.9 fL, MPV have diagnostic sensitivity 80% and specificity 97.8%. Whereas PDW >16.9fL has a sensitivity of 74.5% and specificity of 100% for diabetic microvascular complications (retinopathy, nephropathy, and neuropathy). Conclusion: MPV and PDW may be considered as possible biomarkers for the early detection of diabetic microvascular complications.

scholarly journals To study levels of serum fibrinogen in type 2 diabetes mellitus and its association with diabetic microvascular complications

2017 ◽  
Vol 4 (1) ◽  
pp. 10
Author(s):  
Gurinder Mohan ◽  
Ranjeet Kaur ◽  
Aakash Aggarwal ◽  
Parminder Singh
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
High Serum ◽  
Diabetic Patients ◽  
Coagulation Disorder ◽  
Urine Albumin ◽  
Group A ◽  
Diabetic Microvascular Complications ◽  
Group B

Background: Diabetes mellitus is a hypercoagulable state associated with atherosclerosis leading to development of vascular complications, including microvascular complications.Methods: In our study a total of 60 diabetic patients with duration of diabetes more than 5 years, attending the OPD/ indoor of SGRDIMSR, Amritsar, Punjaqqb, India were included. They were divided in two groups, group A of 30 patients including diabetics with any of the three microvascular complications (diabetic nephropathy, diabetic retinopathy and diabetic neuropathy) and group B of 30 patients including diabetics without any microvascular complication. Group C comprised of 30 age and sex matched non-diabetic subjects who served as controls. Subjects with liver cirrhosis, malignancy or coagulation disorder were excluded. After taking the consent, detailed history taking and detailed physical examination and relevant investigations were done. The serum fibrinogen (hemostasis marker), HBA1C and UACR (urine albumin creatinine ratio) along with routine investigations were measured.Results: It was observed that serum fibrinogen levels were significantly higher in diabetic patients (266.16±54.73 mg/dl) as compared to non-diabetic controls (174.66±18.32 mg/dl); p <0.001.Further, serum fibrinogen levels were found to be significantly higher in diabetic patients with microvascular complications (293.43±51.09 mg/dl) as compared to those without microvascular complications (238.90±44.12); p<0.001.Conclusions: Significantly high serum fibrinogen level was found in diabetic patients as compared to controls and was in positive correlation with development of microvascular complications.

High D-dimer plasma concentration in systemic sclerosis patients: Prevalence and association with vascular complications

2020 ◽  
pp. 239719832095755
Author(s):  
Sofia Furtado ◽  
Bertrand Dunogué ◽  
Georges Jourdi ◽  
Benjamin Chaigne ◽  
Aziza Chibah ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Plasma Concentration ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Macrovascular Complications ◽  
Digital Ulcers ◽  
Tertiary Referral Center ◽  
History Of ◽  
Diffuse Cutaneous Systemic Sclerosis ◽  
D Dimer

Objective: To determine the frequency of elevated D-dimer plasma concentration (>500 ng/mL) in patients with systemic sclerosis and evaluate its association with systemic sclerosis–specific microvascular and macrovascular complications. Methods: Retrospective observational study of patients with systemic sclerosis followed in a tertiary referral center with at least one measurement of D-dimer between 2010 and 2018. Results: A total of 214 patients were analyzed. Mean age at inclusion was 55.1 ± 14.7 years; 180 (84.1%) were female; 74 (34.6%) had diffuse cutaneous systemic sclerosis. Anti-Scl70 and anti-centromere antibodies were positive in 74 (34.6%) and 75 (35.0%) patients, respectively. D-dimer level was elevated in 93 (43.5%) patients, independently of cutaneous subtype (44.6% in diffuse cutaneous systemic sclerosis vs 42.9% in limited cutaneous systemic sclerosis, p = 0.81). At least one microvascular complication was found in 108 (50.5%) patients: 105 (49.1%) with previous or current digital ulcers, 6 (2.8%) with renal crisis, and 4 (1.9%) with pulmonary arterial hypertension. Microvascular complications were more frequent in patients with elevated D-dimer (57.0% vs 45.5%, p = 0.09), significantly so after exclusion of patients with a history of cancer and/or venous thromboembolism (60.5% vs 44.8%, p = 0.04). Macrovascular complications were detected in 15 (7.0%) patients and were associated with a high D-dimer level (11.8% vs 3.3%, p = 0.03). Over a median follow-up of 2.3 years [1.1–3.3] after D-dimer measurement, new macrovascular complications occurred only in patients with high D-dimer (n = 8). Conclusion: High D-dimer levels are frequently found in systemic sclerosis patients and seem to be associated with the occurrence of macrovascular and microvascular complications after adjustment for confounding factors.

scholarly journals miR2Diabetes: A Literature-Curated Database of microRNA Expression Patterns, in Diabetic Microvascular Complications

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 784 ◽  
Author(s):  
Sungjin Park ◽  
SeongRyeol Moon ◽  
Kiyoung Lee ◽  
Ie Byung Park ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Association Studies ◽  
Microvascular Complications ◽  
Expression Patterns ◽  
Disease Model ◽  
Model Organisms ◽  
Web Interface ◽  
Diabetic Microvascular Complications ◽  
User Friendly ◽  
Rats And Mice ◽  
Kidney Liver

microRNAs (miRNAs) have been established as critical regulators of the pathogenesis of diabetes mellitus (DM), and diabetes microvascular complications (DMCs). However, manually curated databases for miRNAs, and DM (including DMCs) association studies, have yet to be established. Here, we constructed a user-friendly database, “miR2Diabetes,” equipped with a graphical web interface for simple browsing or searching manually curated annotations. The annotations in our database cover 14 DM and DMC phenotypes, involving 156 miRNAs, by browsing diverse sample origins (e.g., blood, kidney, liver, and other tissues). Additionally, we provide miRNA annotations for disease-model organisms (including rats and mice), of DM and DMCs, for the purpose of improving knowledge of the biological complexity of these pathologies. We assert that our database will be a comprehensive resource for miRNA biomarker studies, as well as for prioritizing miRNAs for functional validation, in DM and DMCs, with likely extension to other diseases.

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.

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