scholarly journals The role of pro-inflammatory cytokines in diabetic nephropathy in pregnant women with type 1 diabetes mellitus

2013 ◽  
Vol 94 (1) ◽  
pp. 105-110
Author(s):  
G R Gazizova

Diabetic nephropathy is one of the most frequent and unfavorable complications of pregnancy in terms of prognosis in patients with diabetes mellitus. The combination of pregnancy and uncompensated diabetes with such complications as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, leads to overproduction of pro-inflammatory cytokines, thromboses and ischemic necroses of the fetoplacental tissues, and low blood level of immunosuppressive cytokines increases the severity of the disease. This mechanism may be one of the reasons of the spontaneous abortion and pregnancy loss in early pregnancy term in women with diabetes. For a long time the leading role in diabetic nephropathy formation was acknowledged for hyperglycemia, dyslipidemia, oxidative stress, and arterial and renal intraglomerular hypertension. Diabetic nephropathy was recognized as non-immune and non-inflammatory process. Currently diabetic nephropathy is considered as a series of inflammatory reactions involving inflammatory cytokines and chemokines, consisting in the migration of monocytes or macrophages to the kidneys and glomerular and interstitial fibrosis development. Recent studies prove the role of immune-inflammatory reactions in diabetic kidney damage development and confirm an imbalance of the collagen exchange regulating factors, even at the stage of reversible renal dysfunction - microalbuminuria. The close relationship found between hyperglycemia, overproduction of growth factors and nephrosclerosis development in diabetes mellitus. The detection of pro-inflammatory cytokines and fibrogenic growth factors in the urine of patients with diabetes, especially in pregnant women with diabetes, can be used to prompt diagnosis and evaluation of processes occurring in the kidneys, to study the degree of sclerosis, and as a consequence, to predict kidney functional disorders development. Keywords: diabetes mellitus, pregnancy, diabetic nephropathy, cytokines, growth factors.

2021 ◽  
Vol 5 (1) ◽  
pp. 1122-1127
Author(s):  
V. Vasilkova ◽  
◽  
T. Mokhort ◽  
L. Korotaeva ◽  
Y. Yarets ◽  
...  

Aim: to assess the relationship of proinflammatory cytokines and chemokines with the levels of natriuretic peptides in patients with diabetes mellitus (DM). Materials and methods. A total of 155 patients (14 men and 61 women) with type 1 and type 2 diabetes, aged 34 to 84 years, were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of pro-inflammatory cytokines (interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), chemokines (monokine induced by interferon-gamma (MIG), regulated upon activation, normal T cell expressed and presumably secreted (RANTES), growth factors (fibroblast growth factor-23 (FGF-23), vascular endothelial growth factor (VEGF-A), natriuretic peptides (B‐type natriuretic peptide (BNP), N‐terminal fragment of B‐type natriuretic peptide (proBNP). Renal function was assessed based on the levels of serum creatinine, glomerular filtration rate (GFR), which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics. Statistical data analysis was performed using smSTATA 14.2 for Mac (2018). Results. 57% DM patients had BNP and proBNP levels exceeding the diagnostic values of BNP >35 pg/ml and/or proBNP >125 pg/ml. The levels of BNP and proBNP positively correlated with the levels of homocysteine, uric acid, IL-6, С-reactive protein (CRP), high-sensitivity C-reactive protein (hsCRP), A/С, creatinine, cystatin C, TNF-alpha, chemokines (MIG, RANTES), growth factors (FGF-23, VEGF-A) (p <0.05). According to multiple regression analysis, predictors for increased proBNP were IL-6, A/K, creatinine (ß=0.70, p<0.001, ß=3.51, p=0.01, ß=0.97, p=0.01, respectively). ROC analysis determined the highest diagnostic significance of creatinine for the prediction of increased proBNP. The significance of IL-6 proved higher than A/С (AUC-0.777). Thus, when the level of IL-6 (AUC-0.789) was 3.1 mg/ml, the sensitivity and specificity for increased proBNP concentration were 71.9% and 71.2%, respectively. Conclusion. IL-6 might be an independent predictor of increased levels of natriuretic peptide in patients with diabetes. Further study of the role of pro-inflammatory cytokines in the development of cardiovascular diseases will make it possible to finally decode the mechanisms of their pathogenesis, which will further allow us to understand their complex effect on the body and obtain information for the development of new effective and safe specific medicines.


2020 ◽  
Vol 5 (6) ◽  
pp. 355-361
Author(s):  
D. V. Morozenko ◽  
◽  
R. F. Yeromenko ◽  
K. V. Gliebova ◽  
O. P. Timoshenko ◽  
...  

The article considers the issue of disorders of connective tissue metabolism in diabetes mellitus. Glycosylation of structural components of connective tissue and glucose toxicity have been found to determine the pathogenesis of late complications of diabetes mellitus. The most common concept of the pathogenesis of diabetes is metabolic, according to which all variants of diabetes mellitus, including blood vessels, their basement membrane, are associated with primary disorders of lipid, glycoprotein, protein and carbohydrate metabolism due to complete or partial insufficiency. It has been found that the formation of interstitial fibrosis in the kidneys of patients with diabetes begins in the preclinical stages of diabetic nephropathy. The leading cause of interstitial fibrogenesis is hyperglycemia; exacerbate proteinuria fibrosis, activation of the renin-angiotensin system, chronic inflammation and the formation of myofibroblasts in the interstitium. According to the results of the study of aspects of early diagnosis of kidney damage in type 1 diabetes mellitus, it was found that the development of diabetic nephrosclerosis is characterized by qualitative and quantitative changes in collagen composition in the glomeruli and interstitium, rebalance between collagen synthesis and breakdown, glycosaminoglycans, increased synthesis of fibrogenic growth factors and oxidative modification of proteins. The formation of diabetic nephropathy in patients with diabetes is also characterized by the accumulation of collagen types IV and VI, the appearance of interstitial collagen types III and I in the glomeruli, as well as the accumulation of collagen of all types in tubulointerstitium. Quantitative and qualitative characteristics of sulfated glycosaminoglycans of urine in human diabetes indicated different degrees of development of diabetic nephropathy. Glycosaminoglycans hyperexcretion was observed in patients with diabetes mellitus without proteinuria. In patients with microalbuminuria, glycosaminoglycans hyperexcretion was even more pronounced. It was also found that in diabetes, the total excretion of sulfated glycosaminoglycans in the urine doubles. Conclusion. Thus, in diabetes mellitus, an important pathogenetic link in the violation of the morpho-functional state of the kidneys is the degradation of collagen and proteoglycans of the basement membranes of the glomeruli, as well as interstitial fibrosis. This is reflected in changes in urinary glycosaminoglycans excretion, in particular heparansulfate and chondroitin sulfate, which may serve as a marker of proteoglycan metabolism disorders in the kidneys. Patients with diabetes also have an increase in the urine of hydroxyproline, which indicates an increase in the intensity of collagen metabolism in patients


2020 ◽  
Vol 24 (4) ◽  
pp. 46-54
Author(s):  
A. R. Volkova ◽  
V. S. Mozgunova ◽  
M. E. Chernaya ◽  
A. O. Sobenin ◽  
V. M. Lagoyko ◽  
...  

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.


Author(s):  
Suresh Kumar Sethi ◽  
Rajesh Kumar

Background: Hyperglycemia is an important risk factor for the development of diabetic nephropathy. In the initial stages ie micro albuminuria the DKD is clinically detectable and can even be reversed. Hence early screening of diabetic patients is important. Hence the aim of this study was to evaluate the prevalence of nephropathy in a cross section of diabetic patients. Objectives: The Aim of our study was to evaluate the prevalence of nephropathy in recently detected diabetic patients by evaluating microalbuminuria, serum creatinine and creatinine clearance. Methods: A total of 120 patients above 18 years were included in the study and were divided into three groups according to age and were further divided into three groups as per the duration of diseases Patients were again divided into two groups according to the gender. The GFR was calculated as per the MDRD formula and the patients were divided further as per the stage of CKD. Serum Creatinine levels were calculated and the variables associated with CKD were adjusted by Logistic Regression. Results: Our results suggests that 41.25% of subjects were in mild to severe nephropathy out of which 16.25 % were within the three years of diagnosis, thus suggesting the role of early and routine investigation in diabetic patients. Conclusion: Hence the role of life style is clearly emphasized by our results. Although when the variables were adjusted with the logistic regression the occupation was not that significant. Keywords: Albuminuria, Diabetes mellitus (DM), Diabetic Kidney Disease (DKD), Diabetic nephropathy (DN), Serum Creatinine.


Author(s):  
Suresh Kumar Sethi ◽  
Rajesh Kumar

Background: Hyperglycemia is an important risk factor for the development of diabetic nephropathy. In the initial stages ie micro albuminuria the DKD is clinically detectable and can even be reversed. Hence early screening of diabetic patients is important. Hence the aim of this study was to evaluate the prevalence of nephropathy in a cross section of diabetic patients. Objectives: The Aim of our study was to evaluate the prevalence of nephropathy in recently detected diabetic patients by evaluating microalbuminuria, serum creatinine and creatinine clearance. Methods: A total of 120 patients above 18 years were included in the study and were divided into three groups according to age and were further divided into three groups as per the duration of diseases Patients were again divided into two groups according to the gender. The GFR was calculated as per the MDRD formula and the patients were divided further as per the stage of CKD. Serum Creatinine levels were calculated and the variables associated with CKD were adjusted by Logistic Regression. Results: Our results suggests that 41.25% of subjects were in mild to severe nephropathy out of which 16.25 % were within the three years of diagnosis, thus suggesting the role of early and routine investigation in diabetic patients. Conclusion: Hence the role of life style is clearly emphasized by our results. Although when the variables were adjusted with the logistic regression the occupation was not that significant. Keywords: Albuminuria, Diabetes mellitus (DM), Diabetic Kidney Disease (DKD), Diabetic nephropathy (DN), Serum Creatinine.


Author(s):  
Alberto Cuocolo ◽  
Emilia Zampella

Although there has been a marked decline in mortality due to coronary artery disease (CAD) in the overall population in the past three decades, reducing CAD mortality in patients with diabetes mellitus (DM) has proven exceptionally difficult. Several epidemiological studies have shown that DM is associated with a marked increase in the risk of CAD. The symptoms are not a reliable means of identifying patients at higher risk considering that angina is threefold less common in DM than in non-DM. Noninvasive cardiac imaging, such as echocardiography, nuclear cardiology, computed tomography, and magnetic resonance imaging, can provide insight into different aspects of the disease process, from imaging at the cellular level to microvascular and endothelial dysfunction, autonomic neuropathy, coronary atherosclerosis, and interstitial fibrosis with scar formation. In particular, stress myocardial perfusion imaging has taken a central role in the diagnosis, evaluation, and management of CAD in DM patients.


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