scholarly journals Disorders of Proteoglycan and Collagen Metabolism in the Kidneys in Diabetes Mellitus: Clinical and Pathogenetic Mechanisms and Laboratory Markers

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

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.


2020 ◽  
Vol 26 (27) ◽  
pp. 3341-3348 ◽  
Author(s):  
Marek Femlak ◽  
Anna Gluba-Brzozka ◽  
Beata Franczyk ◽  
Jacek Rysz

Introduction: Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study. Methods: The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint. Results: We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous. Conclusion: It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.


2017 ◽  
Vol 21 (2) ◽  
pp. 33-40
Author(s):  
I. N. Bobkova ◽  
A. A. Shchukina ◽  
M. V. Shestakova

THE AIM:to assess excretion value of podocytes injury biomarkers in urine and to clarify their significance for early diabetic nephropathy (DN) diagnostics in diabetes mellitus (DM) patients with different severity of albuminuria (AU)/proteinuria(PU).PATIENTS AND METHODS.74 DM pts were studied, including 30 with type1 DM (T1DM) and 44 pts with type2 DM (T2DM). They were divided into three groups: 41 pts with AU <30 mg/gCr (A1), 13 pts with AU 30-300 mg/gCr (A2), 20 pts with PU (A3). CKD S1 was revealed in 41pts, CKD S2 – in 25 pts, CKD S3 – in 8 pts. Arterial hypertension was observed in 52 pts of 74(70%), mainly in T2DM. 10 healthy subjects were studied as control. Urinary levels of nephrin and podocin (an important slit diaphragm proteins) were measured by ELISA.RESULTS.Nephrinuria (NU) >5,84ng/ml/g, which not detecting in controls, was revealed in 63% of A1 pts, in 77% – in A2, in 80% – in A3. Podocinuria (PdU)>1,73ng/ml/g was revealed in 78% of A1 pts, in 54% of A2 and in 83% – A3. NU in pts with PU was significantly higher than in AU<30 mg/g. PDU in groups with different AU/PU was equally high and has no differ between DM types. Direct correlation was obtained between NU and AU (R=0,947 p<0,05). NU and PdU in T1DM correlated directly with serum creatinine (R=0,489 p<0,05 and R=0,468 p<0,05) and indirectly with GFR (R=-0,461 p<0,05 and R=-0,36 р<0,05). In DM duration less than 5 years NU directly correlated with НbА1с level, in T2DM – indirectly with systolic blood pressure.CONCLUSON. Nephrin and podocin levels can be useful for early diagnostics and monitoring of DN. 


2020 ◽  
Vol 8 (1) ◽  
pp. 16
Author(s):  
Sruthi Kare ◽  
Vishwanath N. Reddy ◽  
Thejdeep Mahamkali

Background: India is one of the epicentres of the global diabetes mellitus pandemic. Rapid socioeconomic development and demographic changes, along with increased susceptibility for Indian individuals, have led to the explosive increase in the prevalence of diabetes mellitus in India over the past four decades. Diabetic Nephropathy is a common consequence of long-standing diabetes mellitus. The development of diabetic nephropathy has a dramatic increase on the morbidity and mortality of patients with diabetes. Objective of this study was to evaluate the prevalence of microalbuminuria in patients with diabetes mellitus patients.  Methods: This cross-sectional study was conducted on T 2 diabetes mellitus patients visiting medicine OPD of R L Jalappa hospital constituent hospital of Sri Deveraj Urs Medical College, Tamaka, Kolar from May 2016 to July 2016. A total of 60 type-2 diabetes patients were enrolled in the study.Results: Average duration of diabetes among study group was 8 years and most of the patients were between 6-10 years. In type 2DM patients, microalbuminuria and glycemic control have shown a significant linear correlation with duration of diabetes (p<0.05). Also, micro albuminuria has a significant correlation with increase in level of glycosylated haemoglobin.  Conclusions: The prevalence of microalbuminuria in diabetic patients was found to be high and being a developing country; there is a dire need that microalbuminuria and HbA1c testing should be done in both, newly diagnosed as well as already diagnosed type 2DM patients as an early marker of renal risk factor.


2020 ◽  
Vol 11 (4) ◽  
pp. 6028-6032
Author(s):  
Ozimboy O Jabbarov ◽  
Botir T Daminov ◽  
Kodirjon T Boboev ◽  
Laylo D Tursunova ◽  
Maxsuma X Tashpulatova ◽  
...  

In the current study, the development of diabetic nephropathy identified the relationship between the polymeric marker of AC genes and the NS3 gene. One hundred twenty-nine patients with type 2 diabetes were tried. Patients in the principle gathering: 65 people with diabetes nephropathy preserved kidney function (33 patients), and kidney function weakness (32 patients), 64 patients with Diabetes were enduring more than 10-20 years, diabetic nephropathy preserved the chain of genotyping polymers carries out kidney function (31 patients). The study showed a link between eNOS3 genes in the development of diabetic nephropathy in Type 2 diabetes patients, supported by the ACE gene.


Sign in / Sign up

Export Citation Format

Share Document