Different Stages Of Diabetic Nephropathy Research Articles

Evaluation of serum levels of sestrin 2 and betatrophin in type 2 diabetic patients with diabetic nephropathy

BackgroundDiabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes mellitus (DM) and the leading cause of chronic kidney disease (CKD) worldwide. Since obesity and type 2 DM (T2DM) are considered as inflammatory conditions, thus reducing their accompanied systemic inflammation may lessen their complications. Sestrin 2 belongs to a group of stress induced proteins which are produced in response to oxidative stress, inflammation and DNA damage. Betatrophin; a hormone that stimulates the growth, proliferation and mass expansion of pancreatic beta-cells and improves glucose tolerance. The objective of the study was to evaluate levels of serum Sestrin 2 and betatrophin in patients with different stages of diabetic nephropathy (DN)) and compare results with healthy control.MethodsThis cross sectional study was carried out on 60 patients above 18 years old, recruited from Tanta University hospitals out patients clinics and 20 apparently healthy individuals of matched sex and age as a control group. Participants were divided into two groups: group I: 20 normal subjects as control group and group II: 60 patients with type 2 DM,. further subdivided in to three equal groups: group 1IIA(20 patients) with normo-albuminuria (ACR < 30 mg/g), group IIB (20 patients) with micro albuminuria (ACR = 30 to 300 mg/g) and group IIC (20 patients) with macro albuminuria (ACR > 300 mg/g). They were subjected to detailed history taking, careful clinical examination and laboratory investigations including blood urea, serum creatinine, estimated glomerular filtration rate (eGFR), urinary albumin creatinine ratio, and specific laboratory tests for Sestrin 2 and Betatrophin by using ELISA technique.ResultsSerum Sestrin 2 significantly decreased, while serum betatrophin level significantly increased in macroalbuminuric group compared to control and other 2 diabetic groups (P value < 0.05). The cut off value of serum sestrin 2 was 0.98 ng/ml with sensitivity 99%, specificity 66% while the cut off value of serum betatrophin was > 98.25 ng/ml with sensitivity 98%, specificity 82%. Serum betatrophin positively correlated with age, fasting, 2 h postprandial, BMI, triglyceride, total cholesterol, serum creatinine, blood urea, UACR, and negatively correlated with eGFR and serum albumin. Serum Sestrin 2 positively correlated with serum albumin. BMI, serum urea, UACR and serum albumin. Serum betatrophin are found to be risk factors or predictors for diabetic nephropathy.ConclusionsPatients with DN, particularly the macroalbuminuria group, had a significant increase in betatrophin levels and a significant decrease in serum Sestrin 2 level. The function of Sestrin 2 is compromised in DN, and restoring it can reverse a series of molecular alterations with subsequent improvement of the renal functions, albuminuria and structural damage.

Biomarkers of Oxidative Stress in Diabetes Mellitus with Diabetic Nephropathy Complications.

The present study aimed to investigate and compare biomarkers of oxidative stress and the activity of antioxidant enzymes in the plasma of patients with different stages of diabetic nephropathy. For this purpose, we studied (1) the levels of reactive oxygen species and reactive nitrogen species as oxidative stress parameters, (2) lipid and protein oxidation, (3) the activity of antioxidant enzymes, and (4) cytokine production. Patients with type 2 diabetes mellitus were divided into three groups according to the loss of renal function: patients with compensated diabetes mellitus with normal renal function DMT2N0 measured as an estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, a group with decompensated diabetes mellitus with complication diabetic nephropathy and mild-to-moderate loss of renal function DMT2N1 (eGFR < 60 mL/min/1.73 m2: 59-45 mL/min/1.73 m2), and a decompensated diabetes mellitus with diabetic nephropathy group with moderate-to-severe loss of renal function DMT2N2 (eGFR > 30 mL/min/1.73 m2: 30-44 mL/min/1.73 m2). All results were compared with healthy volunteers. The results showed that patients with diabetic nephropathy had significantly higher levels of ROS, cytokine production, and end products of lipid and protein oxidation compared to healthy volunteers. Furthermore, patients with diabetic nephropathy had depleted levels of nitric oxide (NO), an impaired NO synthase (NOS) system, and reduced antioxidant enzyme activity (p < 0.05). These findings suggest that patients with impaired renal function are unable to compensate for oxidative stress. The decreased levels of NO radicals in patients with advanced renal complications may be attributed to damage NO availability in plasma. The study highlights the compromised oxidative status as a contributing factor to impaired renal function in patients with decompensated type 2 diabetes mellitus. The findings of this study have implications for understanding the pathogenesis of diabetic nephropathy and the role of oxidative stress and chronic inflammation in its development. The assessment of oxidative stress levels and inflammatory biomarkers may aid in the early detection and prediction of diabetic complications.

Arterial stiffness in patients with type 2 diabetes mellitus at different stages of diabetic nephropathy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Changes of MicroRNA-377 in Diabetic Nephropathy

Background: MicroRNAs (miRNAs) play important roles in modulating gene expression. In cultured mesangial cells, MiR-377 exhibited the greatest change on exposure to high glucose and led to increased fibronectin production in in-vitro diabetic nephropathy. Our aim was to identify the pattern of microRNA-377 changes in human diabetic patients with different stages of diabetic nephropathy. Methods: The study included 45 patients divided into 5 groups; patients with stage 1 & 2 diabetic nephropathy (DN), stage 3 & 4 DN, diabetics without DN, stage 1 & 2 chronic kidney disease (CKD), and stage 3 & 4 CKD. The following tests were done to all patients; serum creatinine, estimated glomerular filtration rate (eGFR), albumin to creatinine ratio, blood sugar, urine analysis, glycated hemoglobin, fundus examination. The RNA was extracted from plasma samples, TaqMan microRNA (miRNA) assays from applied Bio systems were used for analysis of MicroRNA-377. Results: This study found that patients with the highest median of the interquartile range (IQR) of miR-377 were those of group 1 with significant difference between them and all other groups. MiR-377 was significantly correlated with glycated hemoglobin but not with eGFR. Conclusion: Plasma miR-377 is highly significantly increased in human diabetic patients with early rather than late diabetic nephropathy, diabetics without nephropathy, or those at any stage of other causes of CKD. Our findings confirm the role of miR-377 as a potentially novel target in the development of diabetic nephropathy in humans.

Serum calcium and phosphorous balance in diabetic nephropathy and its correlation with glycated hemoglobin

Background: Timely control of hemoglobin A1c (HbA1c) level is very important in patients with diabetic kidney disease. Diabetic nephropathy brings changes in mineral metabolism. The changes in calcium and phosphorous level is a reason for increased morbidity or decreased quality of life in these patients. Conflicting reports are available on serum calcium level and decline in kidney function. This study is to analyse the changes in calcium and phosphorous level in different stages of diabetic nephropathy and its correlation with glycated haemoglobin.Methods: A cross sectional study with 60 diabetic nephropathy patients admitted in MES Medical College for a period of 1.5 years. Patients with cardiac, liver, thyroid dysfunction, under dialysis were excluded from the study. Fasting blood sugar, HbA1c, calcium, phosphorous, creatinine were assessed by VITROS 5600 integrated system. The study population is divided into groups by two different means, according to HbA1c and estimated glomerular filtration rate (eGFR) value. Statistical analysis was performed by statistical package for the social sciences (SPSS) software. Level of significance calculated at 95%.Results: eGFR value showed a highly significant correlation with age (p=0.016), creatinine (p≤0.00001), calcium (p≤0.00001), phosphorous (p≤0.00001) and HbA1c (p=0.00001). There was no significant difference in creatinine and eGFR between male and female subjects. Only eGFR (p=0.0396) showed a significant difference between poor and good glycaemic control groups.Conclusions: This study shows highly significant correlation between the decreased eGFR hypocalcaemia, hyperphosphatemia, increased serum creatinine level and HbA1c. Strict glycemic control is crucial in maintenance of mineral homeostasis and prevention of blood calcium, phosphorous abnormalities.

Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy

This study aimed at comparing the effects of metformin on tubulointerstitial fibrosis (TIF) in different stages of diabetic nephropathy (DN) in vivo and evaluating the mechanism in high glucose (HG)-treated renal tubular epithelial cells (RTECs) in vitro. Sprague–Dawley (SD) rats were used to establish a model of DN, and the changes of biochemical indicators and body weight were measured. The degree of renal fibrosis was quantified using histological analysis, immunohistochemistry, and immunoblot. The underlying relationship between autophagy and DN, and the cellular regulatory mechanism of metformin on epithelial-to-mesenchymal transition (EMT) were investigated. Metformin markedly improved renal function and histological restoration of renal tissues, especially in the early stages of DN, with a significant increase in autophagy and a decrease in the expression of fibrotic biomarkers (fibronectin and collagen I) in renal tissue. Under hyperglycemic conditions, renal tubular epithelial cells inactivated p-AMPK and activated partial EMT. Metformin-induced AMPK significantly ameliorated renal autophagic function, inhibited the partial EMT of RTECs, and attenuated TIF, all of which effectively prevented or delayed the onset of DN. This evidence provides theoretical and experimental basis for the following research on the potential clinical application of metformin in the treatment of diabetic TIF.

The impact of central obesity on the risk of hospitalization or death due to heart failure in type 1 diabetes: a 16-year cohort study

BackgroundObesity and type 2 diabetes are well-known risk factors for heart failure (HF). Although obesity has increased in type 1 diabetes, studies regarding HF in this population are scarce. Therefore, we investigated the impact of body fat distribution on the risk of HF hospitalization or death in adults with type 1 diabetes at different stages of diabetic nephropathy (DN).MethodsFrom 5401 adults with type 1 diabetes in the Finnish Diabetic Nephropathy Study, 4668 were included in this analysis. The outcome was HF hospitalization or death identified from the Finnish Care Register for Health Care or the Causes of Death Register until the end of 2017. DN was based on urinary albumin excretion rate. A body mass index (BMI) ≥ 30 kg/m2 defined general obesity, whilst WHtR ≥ 0.5 central obesity. Multivariable Cox regression was used to explore the associations between central obesity, general obesity and the outcome. Then, subgroup analyses were performed by DN stages. Z statistic was used for ranking the association.ResultsDuring a median follow-up of 16.4 (IQR 12.4–18.5) years, 323 incident cases occurred. From 308 hospitalizations due to HF, 35 resulted in death. Further 15 deaths occurred without previous hospitalization. The WHtR showed a stronger association with the outcome [HR 1.51, 95% CI (1.26–1.81), z = 4.40] than BMI [HR 1.05, 95% CI (1.01–1.08), z = 2.71]. HbA1c [HR 1.35, 95% CI (1.24–1.46), z = 7.19] was the most relevant modifiable risk factor for the outcome whereas WHtR was the third. Individuals with microalbuminuria but no central obesity had a similar risk of the outcome as those with normoalbuminuria. General obesity was associated with the outcome only at the macroalbuminuria stage.ConclusionsCentral obesity associates with an increased risk of heart failure hospitalization or death in adults with type 1 diabetes, and WHtR may be a clinically useful screening tool.

The expression of POMC and AgRP in brain and kidney tissues at different stages of diabetic nephropathy rats

Abstract Objective To explore the changes of proopiomelanocortin (POMC) and Agouti-Related Peptide (AgRP) expression in brain and kidney tissues under insulin intervention at different stages of diabetic nephropathy (DN) rats. Methods The male Sprague-Dawley (SD) rats of DN were treated with high-fat diet for 8 weeks and induced by intraperitoneally injection of streptozotocin (30 mg/kg) for one time. Then DN rats were also injected insulin subcutaneously at 2–5 U/(kg·24 h) from initiation of the streptozotocin. Kidney tissue, blood sample, and 24 h-urine were collected to detect the ratio of kidney/body weight, blood glucose and 24-h urinary albumin excretion rate at different stages (4, 8, 12, and 16 weeks). Immunohistochemistry assay was used to measure the expression of POMC and AgRP at different stages of DN rats. Results The DN rats were established successfully. With the progression of DN, blood glucose, 24-h urinary albumin excretion rate and kidney body weight ratio increased significantly, while decreased when insulin was injected. Immunohistochemistry showed that the expression levels of POMC were decreased gradually in brain and kidney tissues. Conversely, the expression of AgRP in kidney was highest at week 8 and then decreased gradually. The effect of insulin on normalizing POMC and AgRP expression in brain and renal tissues was also observed in DKD rats. Conclusion With the progression of DN, the expression of POMC and AgRP in kidney tissues was observed at different stages of disease, and their expressions were significantly normalized by insulin. The mechanism of in situ expression of POMC and AGRP in kidney to the progression of DN needs further investigations.

Diagnostic efficacy of serum and urinary netrin-1 in the early detection of diabetic nephropathy

This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to...

Evaluation of the Genetic Association and Expressions of Notch-2 /Jagged-1 in Patients with Type 2 Diabetes Mellitus.

Background:Diabetes mellitus (DM) is the world’s most common cause of chronic kidney diseases (CKD), with approximately 1 in 4 adults with DM having CKD and 1 out of 10 to 20% of DM patients die from CKD.Objective:The current study aims to investigate the correlation between Notch-2 and Jag-1expressions and specific inflammation biomarkers IL-1β and IL-6 with different stages of diabetic nephropathy.Methods:From August 2018 to January 2019, three hundred subjects were recruited for this study. One hundred and fifty subjects were healthy and age-matched to the diabetic group and selected as a control group. Another 150 patients with an established diagnosis of type 2 diabetes (T2DM) according to the criteria of the American Diabetes Association (ADA) were also recruited. Blood specimens were eventually used to identify the expressions Notch-2 and Jagged-1 and the levels of inflammatory biomarkers IL-1β and IL-6.Result:The current study shows a significant increase in gene expression and inflammatory biomarkers in patients with moderate and severe diabetic nephropathy compared to the control group. However, there was no significant difference between healthy control and mild diabetic nephropathy patients. This study shows a close association between the increase in the levels of inflammatory biomarkers IL-1β and IL-6 as well as the gene expressions levels of both Notch-2 and Jag-1 with human diabetic nephropathy.Conclusion:According to our findings, we emphasize the use of Notch-2 and Jag-1 expressions and IL-1β and IL-6 levels as potential biomarkers for different stages of diabetic nephropathy.

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

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.

Clinical Significance of Urinary Monocyte Chemoattractant Protein-1 (uMCP-1) and TNF-Alfa in Indian Type 2 Diabetic Patients at Different Stages of Diabetic Nephropathy

Introduction: TNF alfa and Monocyte Chemoattractant Protein-1 (MCP-1) are inflammatory markers upregulated in diabetic nephropathy. This study aims to find the levels of urinary MCP-1 (uMCP-1) and serum TNF alfa levels at different stages of diabetic nephropathy and to see its correlation with UACR(Urinary Albumin Cdeatinine Ratio) in Indian type2 diabetic subjects Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in one year were recruited in this study.Patients were subjected to blood and urine investigations. Groups are Group 1 (control), Group 2 (diabetes with normoalbuminuria), Group 3 (diabetes with microalbuminuria), Group 4 (diabetes with macroalbuminuria). Diabetic Nephropathy were classified according to KIGDO staging. Anthropometric and biochemical details were recorded for all the subjects.UACR calculated by the formula which has been approved by National Kidney Disease Education Program. Urinary MCP-1 and TNF alfa levels were measured by using ELISA. Results: S.urea creatinine, Total cholesterol, TG, LDL, UACR, S.TNF alfa, UMCP1 levels are significantly high in diabetes with macroalbuminuria group (p = 0.01, 0.001, 0.013, 0.01, <0.01, <0.01, <0.01, 0.01 respectively). UACR is positively correlated with umcp1 (r= 0.413 , P=<0.01) and S.TNF alfa (r= 0.218, p=0.008). Increasing uMCP-1, S.TNF alfa levels with the progression of diabetic nephropathy indicating the extent of renal tubular and glomerular damage (p value 0.015,0.008 respectively.) Funding Statement: The authors stated: No funding has been allocated to this research work. Declaration of Interests: The authors declared: There is no conflict of interest. Ethics Approval Statement: This cross-sectional study has been approved by Ethical committee

Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy.

BackgroundDiabetic nephropathy (DN) is a major complication of diabetes and the main cause of end-stage renal disease. Extracellular vesicles (EVs) are small cell-derived vesicles that can alter disease progression by microRNA (miRNA) transfer.MethodsIn this study, we aimed to characterize the cellular origin and miRNA content of EVs in plasma samples of type 2 diabetes patients at various stages of DN. Type 2 diabetes patients were classified in three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. The concentration and cellular origin of plasma EVs were measured by flow cytometry. A total of 752 EV miRNAs were profiled in 18 subjects and differentially expressed miRNAs were validated.ResultsDiabetic patients with microalbuminuria and/or macroalbuminuria showed elevated concentrations of total EVs and EVs from endothelial cells, platelets, leucocytes and erythrocytes compared with diabetic controls. miR-99a-5p was upregulated in macroalbuminuric patients compared with normoalbuminuric and microalbuminuric patients. Transfection of miR-99a-5p in cultured human podocytes downregulated mammalian target of rapamycin (mTOR) protein expression and downregulated the podocyte injury marker vimentin.ConclusionsType 2 diabetes patients with microalbuminuria and macroalbuminuria display differential EV profiles. miR-99a-5p expression is elevated in EVs from macroalbuminuria and mTOR is its validated mRNA target.

Dietary intake in type 1 diabetes at different stages of diabetic kidney disease

AimDiet plays an important role in the kidney health of individuals with type 1 diabetes. However, not much is known about dietary practices at different stages of diabetic nephropathy. We aimed at investigating food intake, dietary patterns, and nutrient intakes in individuals with type 1 diabetes differing in renal status. MethodsData were available from 1874 individuals with type 1 diabetes (45% men, age 48 ± 13 years). Diet was assessed at the levels of food items and diet patterns (diet questionnaire), and energy and nutrient intakes (food record). Six groups were formed based on the eGFR or dialysis and transplantation status. ResultsReductions in liquid-milk product and salt consumption, and increase in special diet adherence were observed at the early stages of eGFR decline. Reduced coffee consumption was observed after eGFR was <30 ml/min/1.73 m2. With advancing kidney failure, rye bread consumption decreased, but that of wheat bread increased. Compared to those with intact kidney function (the index group), the Fish and vegetable diet pattern scores were higher in individuals with mildly-to-severely decreased eGFR. Instead, the Sweet pattern scores were lower than in the index group in all other groups. Energy intake was lower in all groups compared to those with intact kidney function. Advancing kidney failure was associated with reductions in protein intake per body weight, and in the intakes of sodium, potassium, calcium, and phosphorus. ConclusionsDifferences in the dietary intake are seen already at the early stages of kidney function decline.

Significance of glycated LDL in different stages of diabetic nephropathy

AimThe aim of this study was to investigate the role of elevated glycated LDL (low-density lipoprotein) in the progression of diabetic kidney disease among type 2 diabetes (T2D) subjects. Materials and methodsThis case-control observational study is a part of Saudi Diabetes Kidney Disease (SAUDI-DKD) study conducted during the period from April 2014 to June 2015. This study cohort is divided into two groups; the first group was T2D patients without diabetic nephropathy (DN) (n = 24) and the second group was T2D with DN (n = 45). Serum glycated LDL levels were determined by ELISA. Pearson's correlation analysis was performed, and the diagnostic accuracy was assessed using the area under the ROC curve. ResultsThere was a threefold increase of serum glycated LDL level among diabetic subjects when compared with non-diabetic subjects and this level progressively increased with the progression of DN. The glycated LDL was found to have a significant diagnostic accuracy with AUC of 0.685 and 0.775 for cases with microalbuminuria and macroalbuminuria respectively. ConclusionThe glycated LDL could play a significant role in predicting diabetic patients who are susceptible to develop DN among T2D patients.

Medical prevention through mathematical models: assessing the evolution of diabetic complications

The aim of the study was to evaluate hemorheological changes in diabetic patients with renal complications, also to observe the influence of biological parameters in blood viscosity and to determine the progresion of dissease by using a mathematical model with multiple lineary regression equation in the intent of limiting the evolution of diabetic nephropathy.The study compared rheological and biological measurements in 21 patients with different stages of diabetic nephropathy, controlled with a subset of 18 healthy subjects. Progressive inclusion of the different rheological and biological parameters resulted into a mathematical model according with their statistically significant relevance and renal involvement.Results demonstrated a strong dependency of at least five parameters that can be modifiable through proper therapy and diet and may influence the viscosity of blood and, implicitelly, the micro-vascular complications of diabetes mellitus.

Application of shear wave elastography in the study of renal tissue elasticity in patients with diabetic nephropathy

Objective To investigate the clinical value of real-time shear wave elastography(SWE) in early diagnosis of diabetic nephropathy(DN). Methods One hundred and fifty-five patients with type 2 diabetes mellitus (DM) in our hospital were selected as DN group and 54 healthy volunteers with matched age-sex were selected as control group. According to the criteria of Mogensen staging, patients of DN group were divided into 3 subgroups according to urine protein/creatinine (ACR): group A (DM or DN Ⅰ, Ⅱ), ACR 300 mg/g. All subjects were examined by SWE technique to detect the maximum, mean and minimum Young′s modulus values (Emax, Emean, Emin) of the middle of left renal parenchyma, the values of Young′s modulus in the control group and DN patients were compared. The relationship between Young′s modulus and ACR in patients with DN was analyzed. Results The Emax, Emean and Emin in DN patients were all greater than those in control group (P<0.05). In group A, B and C, Emax, Emean and Emin gradually increased (P<0.05). Spearman correlation analysis showed that there was a positive correlation between Young′s modulus and ACR in patients with DN (r=0.817, 0.764, 0.609; all P=0.000). ROC curve analysis showed that the area under the curve of Emax diagnosis DN Ⅲ stage was 0.810, the cut-point value was 6.65 kPa, the sensitivity was 79.0%, and the specificity was 81.7%; the area under the curve of Emean diagnosis DN Ⅲ stage was 0.785, and the cut-off value was 3.69 kPa, sensitivity 62.8%, specificity 78.3%. Conclusions SWE technique can quantitatively analyze renal parenchyma hardness in patients with different stages of DN, which may provide new diagnostic information for early diagnosis of DN. Key words: Ultrasonography; Diabetic nephropathy; Shear-wave elastography; Renal parenchyma elasticity

Pathological significance of urinary complement activation in diabetic nephropathy: A full view from the development of the disease.

Aims/IntroductionThe aim of the present study was to obtain a full view of the changes of urinary complement activation products in the development of diabetic nephropathy and explore their possible significance in the disease process.Materials and methodsA total of 62 patients at different stages of diabetic nephropathy, 20 diabetes patients without nephropathy and 20 healthy persons were enrolled. Urinary complement activation products, including C3a, C5a and C5b‐9, were measured, and their associations with the progression of the disease were analyzed.ResultsThe urinary complement activation products increased markedly since the proteinuria stage, and were parallel with the progression of diabetic nephropathy. More severe renal tubular damage was observed in patients with higher levels of urinary complement activation products. The urinary complement activation products levels correlated closely with renal tubulointerstitial injury score and relative tubular interstitial volume. Multivariate regression analysis showed that elevated urinary complement activation products were independent risk factors for tubular injury in diabetic nephropathy patients.ConclusionsUrinary complement activation might have a role in renal tubular interstitial injury in patients with diabetic nephropathy, especially in patients at a later stage of the disease.

Correlation Between Different Stages of Diabetic Nephropathy and Neuropathy in Patients with T2DM: A Cross-Sectional Controlled Study

IntroductionEarly detection of diabetic peripheral neuropathy (DPN) is critical in patients with type 2 diabetes mellitus (T2DM) due to the lack of targeted therapy for DPN. We have investigated the relationship between different stages of diabetic nephropathy and DPN in an attempt to elucidate whether albuminuria can be used as an early warning signal of DPN progression.MethodsA total of 217 T2DM patients who met the inclusion criteria were recruited from the Department of Endocrinology, Nanfang Hospital between January 2016 and June 2016. These patients were placed in groups based on urinary albumin excretion rate (UAER) and estimated glomerular filtration rate. Nerve conduction studies, the Semmes–Weinstein monofilament test (SWMT) and the vibration perception threshold (VPT) test were conducted. Multiple linear regression analysis, multivariate logistic regression and receiver-operating characteristic (ROC) analysis were performed to investigate the relationship between different stages of diabetic nephropathy and DPN in these patients.ResultsSignificant differences were observed in the conduction velocity (CV) and amplitude of sensory/motor nerve potential among the T2DM patients at different stages of diabetic nephropathy (all p < 0.05). The UAER and duration of diabetes were found to be independent factors associated with the mean CV and amplitude of sensory/motor nerve potential (all p < 0.05). A disease duration of > 10 years (p = 0.025) and a higher total cholesterol value (p = 0.024) were found to be significantly associated with abnormal SWMT results. A UAER of > 300 mg/24 h (p = 0.007) and a diastolic blood pressure of > 100 mmHg (p = 0.042) were associated with a higher risk for abnormal VPT. A UAER of > 300 mg/24 h (p < 0.001) and a disease duration of > 10 years (p = 0.02) were observed to be significantly correlated with DPN. The ROC analysis showed that the optimal cutoff values of UAER and duration as indicators of DPN were 90.5 mg/24 h and 9.5 years, respectively (both p < 0.001).ConclusionsThe results suggest that diabetic nephropathy is closely associated with the development of DPN in T2DM patients and that UAER and disease duration can be used as warning indicators of DPN progression.Chinese Clinical Trials Register NumberChiCTR-ROC-16007701.

Risk of coronary artery disease and stroke according to sex and presence of diabetic nephropathy in type 1 diabetes.

To determine the effect of different stages of diabetic nephropathy (DN) and sex on the excess and absolute morbidity of coronary artery disease (CAD) and stroke in people with type 1 diabetes (T1D) in order to distinguish different cardiovascular disease (CVD) risk profiles in people with T1D. The study included 4410 people with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane), divided by DN status, and a control population of 12 434 people without diabetes. CVD events were identified from the Finnish nationwide health registries. Cumulative incidences for CAD and stroke were calculated and standardized incidence ratios (SIRs) were estimated between participants with T1D and the control group, stratified by DN status and sex. There were 487 incident CADs and 290 strokes at the end of 2014 (median follow-up 12.9 years). The cumulative incidence rates of CAD and stroke were similar in men and women within different nephropathy groups. The SIR for CAD was 7.5 (95% confidence interval [CI] 6.9-8.2), 17.2 (95% CI 14.9-19.5) in women and 5.3 (95% CI 4.7-5.9) in men. The women-to-men ratio of SIR increased by nephropathy group: 3.3, 3.7, 5.3 and 6.8 in the normo-, micro- and macroalbuminuria and end-stage renal disease (ESRD) groups, respectively. The SIR for stroke was 5.0 (95% CI 4.3-5.5), similar in men and women. The women-to-men ratio of SIR for stroke was 0.8, 1.3, 1.6 and 1.7, in the normo-, micro- and macroalbuminuria and ESRD groups, respectively. The SIR in participants with normoalbuminuria and an estimated glomerular filtration rate ≥90 mL/min/1.73 m2 was 3.5 (95% CI 2.5-4.5) for CAD and 1.6 (95% CI 1.0-2.3) for stroke. Although the excess CVD risk is several-fold greater in women compared to men, the absolute CVD risk in men and women was equal when nephropathy was taken into account. Even participants with normoalbuminuria and normal kidney function were found to have an excess CVD risk compared with the control group without diabetes.