Towards Better Drug Repositioning: Targeted Immunoinflammatory Therapy for Diabetic Nephropathy

2019 ◽  
Vol 26 ◽  
Author(s):  
Qin zhang ◽  
Ming Yang ◽  
Ying Xiao ◽  
Yachun Han ◽  
Shikun Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Inflammatory Process ◽  
Drug Repositioning ◽  
Microvascular Complications ◽  
Pathogenic Factor ◽  
Progressive Decline ◽  
Functional Changes ◽  
Sequence Of Events ◽  
Novel Treatment

: Diabetic nephropathy (DN) is one of the most common and important microvascular complications of diabetes mellitus (DM). The main clinical features of DN are proteinuria and a progressive decline in renal function , which are associated with structural and functional changes in the kidney. The pathogenesis of DN is multifactorial, including genetic, metabolic and haemodynamic factors, which can trigger a sequence of events. Controlling metabolic risks such as hyperglycaemia, hypertension and dyslipidaemia is not enough to slow the progression of DN. Recent studies have emphasized immunoinflammation as a critical pathogenic factor in the progression of DN. Therefore, targeting inflammation is considered a potential and novel treatment strategy for DN. In this review, we will briefly introduce the inflammatory process of DN and discuss the anti-inflammatory effects of antidiabetic drugs when treating DN.

STUDY OF PREVALENCE AND CLINICAL PROFILE OF NEPHROPATHY AND RETINOPATHY IN TYPE 2 DIABETES PATIENTS AT TERTIARY CARE CENTER, UDAIPUR

2021 ◽  
pp. 6-8
Author(s):  
Yash Salil Patel
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Tertiary Care ◽  
Positive Family History ◽  
Diabetic Patients

Microvascular complications of Type 2 Diabetes Mellitus (T2DM), (retinopathy and nephropathy) have a similar etiopathogenetic mechanism besides genetic predisposition. Even though these two complications frequently co-exist, their frequency varies. The association of these two signicant complications and their coexistence needs a relook. To study prevalence of retinopathy and nephropathy in Type 2 diabetes mel Aim: litus. Comparison of diabetic retinopathy and nephropathy in Type 2 diabetes mellitus and its correlation of diabetic retinopathy and nephropathy with duration of illness and various risk factors that affects development, progression and severity of diabetic retinopathy and nephropathy. 100 diabetic patients were taken up for study for a period of one year meeti Methodology: ng the criteria for the present study. Detailed history was taken from patient and meticulous examination was done of all patients with special emphasis on renal and ophthalmic symptoms. Clinical data and investigation prole was tabulated. Statistical analysis was done. Among 100 patients, 22 had diabetic retinopathy. Among patients with diab Results & Conclusion: etic retinopathy, 68.18% patients had positive family history. Among 100 patients, 32 had diabetic nephropathy, mean FBS was 207 mg%, PPBS was 317.8 mg% and mean HbA was 9.2%. Among patients with diabetic retinopathy, mean FBS was 211 mg%, PPBS was 324.9 1c mg%, HbA was 9.5%. From this study it is found that diabetic nephropathy starts earlier than retinopathy. In this study 1c hypertension was found to accelerate progression into nephropathy and retinopathy.

scholarly journals ALTERATIONS OF LIPID LEVELS MAY INDUCE THE INSULIN RESISTANCE IN TYPE TWO DIABETES MELLITUS: A SYSTEMIC REVIEW

2020 ◽  
pp. 9-20
Author(s):  
DIVYA JYOTHI P ◽  
DOONDI PHANI KUMAR N ◽  
VINAY MOHAN A ◽  
RAMYA A
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Microvascular Complications ◽  
Hormone Secretion ◽  
International Diabetes Federation ◽  
The Body ◽  
Systemic Review ◽  
Cardiac Complications ◽  
Sequence Of Events ◽  
Chronic Hyperglycemia

Diabetes mellitus (DM) is not one disorder; it represents a series of metabolic conditions related to hyperglycemia and caused by defects in hormone secretion and hormone action. Exposure to chronic hyperglycemia may result in microvascular complications in the retina (diabetic retinopathy), kidney (diabetic nephropathy), neuron (diabetic-neuropathy), skin, foot, and cardiac complications (stroke, hypertension…etc.). International Diabetes Federation estimates that 1.1 million children and adolescents aged 14–19 years have type one DM. Without interventions to halt the increase in diabetes, there will be at least 629 million people living with diabetes by 2045. In the body, white adipose tissue is the leading site for the storage of excess energy produced from the food intake in large quantities, of the development of insulin resistance (IR) and type 2 DM by the over intake of fatty acid in the body. It results in the accumulation of fatty acyl co-A (FA-CoA) within the myocytes. It leads to improper signaling of the insulin and reduces the level in the myocytes and pancreases beta cells. It combines with genetically reduces the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) coactivator-1, initiates the inflammation process by the activation of the tumor necrotic factor alpha and protein kinase C. These alterations lead to further increase the intramyocellular FA-CoA and triglycerides. The sequence of events may develop mitochondrial dysfunction in the sarcolemma outer layers. Finally improves IR also with increasing intramyocellular lipids. This concept might be helpful to those who are pursuing endocrinology specialization, nursing staff, pharmacists, and other medical departments.

Microvascular Complications of Type 2 Diabetes Mellitus

2020 ◽  
Vol 18 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Charles Faselis ◽  
Alexandra Katsimardou ◽  
Konstantinos Imprialos ◽  
Pavlos Deligkaris ◽  
Manolis Kallistratos ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Sexual Dysfunction ◽  
Microvascular Complications ◽  
Diagnostic Methods ◽  
Laboratory Evaluation

Background: Type 2 diabetes mellitus (T2DM) is a chronic, non communicable, multisystem disease that has reached epidemic proportions. Chronic exposure to hyperglycaemia affects the microvasculature, eventually leading to diabetic nephropathy, retinopathy and neuropathy with high impact on the quality of life and overall life expectancy. Sexual dysfunction is an often-overlooked microvascular complication of T2DM, with a complex pathogenesis originating from endothelial dysfunction. Objective: The purpose of this review is to present current definitions, epidemiological data and risk factors for diabetic retinopathy, nephropathy, neuropathy and sexual dysfunction. We also describe the clinical and laboratory evaluation that is mandatory for the diagnosis of these conditions. Method: A comprehensive review of the literature was performed to identify data from clinical studies for the prevalence, risk factors and diagnostic methods of microvascular complications of T2DM. Results: Diabetic nephropathy and retinopathy affect approximately 25% of patients with T2DM; diabetic neuropathy is encountered in almost 50% of the diabetic population, while the prevalence of erectile dysfunction ranges from 35-90% in diabetic men. The duration of T2DM along with glycemic, blood pressure and lipid control are common risk factors for the development of these complications. Criteria for the diagnosis of these conditions are well established, but exclusion of other causes is mandatory. Conclusion: Early detection of microvascular complications associated with T2DM is important, as early intervention leads to better outcomes. However, this requires awareness of their definition, prevalence and diagnostic modalities.

scholarly journals Association of 2184AG Polymorphism in the RAGE Gene with Diabetic Nephropathy in Chinese Patients with Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Cai ◽  
Jian Li ◽  
Ji-Xiong Xu ◽  
Ying Liu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Chinese Patients ◽  
Chinese Han ◽  
Genotype Frequencies ◽  
Diabetic Microvascular Complications

Objective. The interaction between advanced glycation end products and their cellular receptor (RAGE) has an important role in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the relationship between the 2184A/G polymorphism in the RAGE gene and diabetic nephropathy in Chinese Han patients with type 2 diabetes mellitus. Methods. A total of 868 patients with type 2 diabetes mellitus (486 without and 382 with diabetic nephropathy) were enrolled in this study. The genotype and allele frequencies of the 2184A/G polymorphism were detected using the polymerase chain reaction-restriction fragment-length polymorphism method. Results. The G allele and AG + GG genotype frequencies in patients with diabetic nephropathy were significantly lower than those in patients without diabetic nephropathy (P=0.001 and P=0.005, resp.). After adjustments for possible confounders, multivariate logistic regression analyses showed that the 2184A/G polymorphism was independently associated with diabetic nephropathy (OR = 0.46, 95% CI: 0.22–0.92, P=0.028). Conclusions. Our study indicated that the 2184A/G polymorphism in the RAGE gene was significantly associated with diabetic nephropathy in Chinese Han patients with type 2 diabetes.

Wnt signaling and podocyte dysfunction in diabetic nephropathy

2017 ◽  
Vol 65 (8) ◽  
pp. 1093-1101 ◽  
Author(s):  
Madhura Bose ◽  
Sadia Almas ◽  
Sharma Prabhakar
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Diabetic Nephropathy ◽  
Wnt Signaling ◽  
Therapeutic Strategies ◽  
Podocyte Injury ◽  
Functional Changes ◽  
Terminal Renal Failure ◽  
Cardiovascular Morbidity And Mortality

Nephropathy is a major microvascular complication of diabetes mellitus and often leads to terminal renal failure in addition to contributing significantly to cardiovascular morbidity and mortality. Despites continuous advances, the pathogenesis of diabetic nephropathy remains poorly understood. Recent studies have underscored the significance of structural and functional changes in podocytes in the development and progression of diabetic nephropathy. The role of podocytes in health and diabetic nephropathy and abnormalities including podocyte hypertrophy, effacement, and apoptosis, and a detailed discussion on the role played by the Wnt-β-catenin signaling pathway in podocyte injury and dysfunction are the focus of this review. In addition, the role played by Wnt signaling in mediating the effects of known therapeutic strategies for diabetic nephropathy is also discussed.

scholarly journals Structural and functional changes of the heart in patients with diabetic nephropathy undergoing hemodialysis

2019 ◽  
pp. 39-48
Author(s):  
O. B. Susla ◽  
Z. I. Litovkina ◽  
O. V. Bushtynska
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Cardiac Remodeling ◽  
Systolic Dysfunction ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Valve Calcification ◽  
Adequate Treatment ◽  
Functional Changes

Systematic analysis of cardiac remodeling peculiarities in patients with V D stage of chronic kidney disease (CKD VD)  caused by diabetes mellitus is important both in the stratification of cardiovascular risk and in the choice of adequate treatment strategies. The purpose of the study was to determine the character of structural and functional reconstruction of myocardium in patients with diabetic nephropathy (DN) on maintenance hemodialysis (HD) by identifying left ventricular hypertrophy (LVH), its geometric types, assessment of the severity of heart dysfunction, pulmonary hypertension (PH), as well as determination of frequency of cardiac valve calcification (CVC), development of defects of mitral (MV) and aortic (AV) valves. Materials and methods. The study included 136 patients on chronic HD (men, 78, age, (53,9±1,0) years, duration of HD, (47,6±4,2) months). Depending on the presence/absence of type 2 diabetes mellitus (DM) with kidney damage, they were divided into two groups: the first one – without DN (n=88); the second one – with DN (n=48). All patients were followed up by standard echocardiography (EchoCG) examination by standard procedure. Results. LVH was diagnosed in 84.6% of patients with CKD VD stage, significantly more often (93.8 vs. 78.4%, p=0.020) in patients with DN, with the incidence of eccentric LVH in the second group being higher (47.9 vs. 28.4%, p=0.023) than in the first one. Prevalence of pseudonormal and restrictive types of LV diastolic dysfunction (62.5 vs. 28.4%, p<0.001), LV systolic dysfunction (27.1 vs. 9.1%, p=0.006) and PH (64.6 vs 35.2%, p=0.001) were significant in HD patients with DN. CVC was detected in 66.6% of patients with type 2 DM with renal injury with a predominance of calcification of both valves (35.4%) over isolated calcification of MV (MVC) (20.8%) and AV (AVC) (10.4 %). Combined valve calcification in the HD patients of the second group was observed 2.6 times more often (p=0.003) than in the first one. Patients with DN, unlike those without diabetes, were associated with a higher prevalence of stenoses of MV (16.7 vs. 3.4%, p=0.007) and AV (39.6 vs. 15.9%, p=0.004), and insufficiency of MV (66.7 vs. 44.3%, p=0.013) and AV (35.4 vs. 14.8%, p=0.006). The most significant EchoCG parameters that distinguished groups of HD patients with the presence of DN were: left atrial diameter (p<0.001), end-diastolic LV dimension (p<0.001), thickness of interventricular septum (p=0.001), LV myocardial mass index (p=0.001), ratio of transmitral flows in early and late diastole (p=0.009), time of deceleration of early diastolic transmitral blood flow (p<0.001), LV ejection fraction (p=0.009), diameter of the right ventricle (RV) (p=0.003), diameter (p=0.007) and mean pulmonary artery pressure (p<0.001). Conclusions. In patients with CKD VD stage with DN the maladaptive cardiac remodeling with predominance of unfavorable types (eccentric (to a greater extent) and concentric) LV hypertrophy, RV dilatation, PH, expressive of LV diastolic and systolic dysfunction, large-scale combined MVC and AVC occurs, which, in turn, leads to the formation of valve defects, can contribute to the progression of diastolic myocardial stiffness and heart failure.

Glycemic variability in patients with diabetes mellitus and different stages of diabetic nephropathy

2020 ◽  
Vol 24 (4) ◽  
pp. 46-54
Author(s):  
A. R. Volkova ◽  
V. S. Mozgunova ◽  
M. E. Chernaya ◽  
A. O. Sobenin ◽  
V. M. Lagoyko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Glucose Homeostasis ◽  
Energy Homeostasis ◽  
Microvascular Complications ◽  
Glycemic Variability ◽  
Advantages And Disadvantages ◽  
Glucose Reabsorption ◽  
Patients With Diabetes

The relevance of the study of glycemic variability in patients with diabetes mellitus and diabetic nephropathy is due to disability of the able-bodied population and high mortality against the background of the almost irreversible progression of diabetic nephropathy. The article highlights modern ideas about the influence of various factors on the occurrence of diabetic nephropathy and its course. The article is devoted to a review of current recommendations on diabetes mellitus and diabetic nephropathy; the etiopathogenesis of diabetic nephropathy was described in detail. The role of the kidneys in glucose homeostasis, renal gluconeogenesis, and glucose reabsorption by the kidneys in healthy and in pathology is described. Detailed expositions of glycemic variability parameters, their changes in patients with diabetes mellitus depending on the stage of diabetic kidney damage are presented. The role of the kidneys in maintaining energy homeostasis, impaired glucose homeostasis in conditions of chronic kidney disease is described. We analyzed different options for insulin therapy, their advantages, and disadvantages in patients with diabetes mellitus with diabetic nephropathy. The presented material is extremely relevant for the development and implementation in the clinical practice of glycemic control methods to optimize treatment tactics, prevent the formation of microvascular complications, and early disability of patients with diabetes mellitus.

scholarly journals Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Kholoud Shalaby ◽  
Rania Bahriz ◽  
Nancy Mahsoub ◽  
Mohammed M. El-Arman ◽  
Ghada El-Said
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Gene Polymorphism ◽  
Matrix Metalloproteinase ◽  
Microvascular Complications ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

Abstract Background Matrix metalloproteinase 9 (MMP-9) is an important inflammatory marker in diabetic nephropathy. Many studies assessed the association between MMP-9 gene polymorphism and different microvascular complications of type 2 diabetes mellitus, though the results were inconclusive and need further exploration. Our study aimed to assess the association between MMP-9 -1562C/T gene polymorphism and diabetic nephropathy in patients with type 2 diabetes mellitus. Results Taking CC genotype of rs3918242 (MMP-9-1562C/T SNP) as the reference genotype and C as the reference allele, TT genotype, T allele showed significantly lower frequency in diabetic nephropathy group than without nephropathy (2.9% versus 20%, 20% versus 35.7% respectively), with the possible significant protective effect against diabetic nephropathy development (OR = 0.269, 0.450 respectively); it was considered as an independent predictor for diabetic nephropathy occurrence. Conclusions This study suggested that T allele of MMP-9 -1562C/T single nucleotide polymorphism had a protective role against diabetic nephropathy development and also had a role for early prediction of patients susceptible to this complication, so it helps in prevention and management of those patients.

scholarly journals Relationship between Serum Asymmetric Dimethylarginine Level and Microvascular Complications in Diabetes Mellitus: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Jing Liu ◽  
Caiying Li ◽  
Wen Chen ◽  
Kuanrong He ◽  
Huijuan Ma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Publication Bias ◽  
Asymmetric Dimethylarginine ◽  
Meta Analysis ◽  
Microvascular Complications ◽  
Healthcare Research ◽  
Significant Heterogeneity ◽  
Statistical Heterogeneity ◽  
The Difference

Objective. The purpose of the meta-analysis was to evaluate the relationship between serum asymmetric dimethylarginine (ADMA) level and microvascular complications in diabetes mellitus (DM) including diabetic retinopathy (DR), diabetic neuropathy (DN), and diabetic nephropathy. Methods. Studies were comprehensively identified by searching Web of Science, Embase, and PubMed databases up to August 30, 2018. The meta-analysis was carried out to compare the difference of serum ADMA concentrations of DR, DN, and diabetic nephropathy patients with healthy controls. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality were applied to assess the methodological quality. Chi-squared Q test and I2 statistics were applied to evaluate statistical heterogeneity. Subgroup analyses were conducted and publication bias was assessed by Egger’s test. Result. Ten studies were finally entered in the meta-analysis. Statistically significant heterogeneity was observed across these studies (I2 = 77.0%, p < 0.001). Compared with DM without microvascular complications, circulating level of ADMA was significantly higher in DM with microvascular complications (all p < 0.05). Sensitivity analysis suggested that the results of this meta-analysis were shown to be stable. There was no significant publication bias (P=0.823). Conclusion. Elevated ADMA levels correlate with diabetic microangiopathies such as DR and diabetic nephropathy. ADMA may play an important role in the pathobiology of microvascular complications of diabetes.

scholarly journals Diabetic microvascular complications(retinopathy and nephropathy) and pregnancy

2013 ◽  
Vol 62 (2) ◽  
pp. 75-82 ◽  
Author(s):  
Natalya Viktorovna Borovik ◽  
Vladimir Vsevolodovich Potin ◽  
Yelena Leonidovna Rutenburg
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Diabetes Mellitus Type 1 ◽  
Diabetes Mellitus Type ◽  
Diabetic Microvascular Complications

Dynamics of diabetic nephropathy and diabetic retinopathy in 134 women with diabetes mellitus type 1 was studied. It was shown that pregnancy doesn’t lead to aggravation of diabetic nephropathy and diabetic retinopathy. Manifestation of transit maculopathy in some women was related to higher hypoglycemic condition rate.

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