Occurrence Of Diabetic Nephropathy Research Articles

The Generation and Treatment of Diabetic Nephropathy are Discussed from Deficiency, Blood Stasis, Dampness and Turbidity

Deficiency, stasis, dampness and turbidity are common clinical pathogenic factors, which have been confirmed in many fields for years, and many studies have shown that diabetic nephropathy is associated with the upper four diseases. This paper demonstrates the correlation and treatment with the occurrence of diabetic nephropathy from four aspects of deficiency, stasis, dampness and turbidity, as a clinical reference.

Correlation between Red Cell Distribution Width (RDW) and Mean Corpuscular Volume (MCV) as a Prognostic Biomarker for Diabetic Nephropathy Patients in a South Indian Hospital

Context: Diabetic nephropathy is one of the microvascular complications of diabetes mellitus, capable of leading to end-stage renal disease. Diabetic nephropathy could only be identified through renal biopsy testing, which is expensive and can impose a financial burden on patients. Therefore, there is a necessity to develop a cost-effective method for identifying diabetic nephropathy. Aim: To evaluate the correlation between RBC parameters, such as RDW and MCV values, as prognostic biomarkers for patients with diabetic nephropathy. Methods and Material: Study Design: Prospective comparative study. Study Site: Sudha Institute of Medical Science, Erode. Study Duration: Study was carried out over six-months. Sample Size: 101 diabetic nephropathy patients and 101 type 2 diabetes mellitus patients. Statistical Analysis: Pearson correlation. Results: The majority of diabetic nephropathy patients were 40 years old or older, and most of them were males. Among the study participants, a significant number of male participants had habits of smoking and alcohol consumption. The duration of diabetes and BMI exhibited a strong correlation with the occurrence of diabetic nephropathy. Furthermore, there were notable increases in urea, creatinine, FBS, RBS, PPBS, and HbA1C, alongside a decrease in MCV and eGFR as diabetic nephropathy progressed. Conclusions: Our research indicates a positive correlation between RDW and HbA1c, FBS, RBS, PPBS, urea, and creatinine. In contrast, negative correlation of RDW with MCV and eGFR. MCV is negatively correlated with HbA1c, FBS, RBS, PPBS, urea, creatinine. In contrast, positive correlation between MCV and eGFR.

Single-cell transcriptomes reveal a molecular link between diabetic kidney and retinal lesions

The occurrence of diabetic nephropathy (DN) and diabetic retinopathy (DR) are closely associated in patients with diabetes. However, the cellular and molecular linkage of DN and DR has not been elucidated, and further revelations are needed to improve mutual prognostic decisions and management. Here, we generate and integrate single-cell RNA sequencing profiles of kidney and retina to explore the cellular and molecular association of kidney and retina in both physiological and pathological conditions. We find renal mesangial cells and retinal pericytes share molecular features and undergo similar molecular transitions under diabetes. Furthermore, we uncover that chemokine regulation shared by the two cell types is critical for the co-occurrence of DN and DR, and the chemokine score can be used for the prognosis of DN complicated with DR. These findings shed light on the mechanism of the co-occurrence of DN and DR and could improve the prevention and treatments of diabetic microvascular complications.

The prevalence of diabetic peripheral neuropathy in youth with diabetes mellitus.

Diabetic neuropathy (DN) is a serious complication in diabetes mellitus. We aimed to determine the prevalence of DN in pediatric-onset diabetes in a tertiary care center and to assess the sensitivity and specificity of monofilament testing and noninvasive screening to diagnose DN compared with the gold standard nerve conduction study (NCS). Sixty-five Thai children and adolescents (39 females) diagnosed with diabetes before 15 years of age were included. All subjects were screened for DN by foot and neurological examinations, light touch sensation by 10 g Semmes-Weinstein monofilaments, and the Michigan Neuropathy Screening Instrument (MNSI). NCSs were used as the gold standard for diagnosis of DN. Fifty-eight patients had type 1 diabetes ( T1D), 5 patients had type 2 diabetes, and 2 patients had other types of diabetes. The mean age was 17.7±4.6 years (8-33 years). The prevalence of DN in this cohort was 12.3% by NCS. All subjects were asymptomatic. Mean diabetes duration did not differ between the groups (with DN 8.0±3.0 years vs. no DN 8.2±5.0 years). Notably, one patient with T1D developed DN within 3 years after diagnosis. Poor glycemic control was a significant risk factor for DN. Glycosylated hemoglobin was higher in the DN group (10.6%±2.3% vs. 8.5%±1.6%, P=0.008). The occurrence of diabetic nephropathy was associated with DN (prevalence rate ratio, 4.97; 95% confidence interval, 1.5-16.46). Foot and neurological examinations, monofilaments, and the MNSI failed to detect DN in all subjects with abnormal NCS. The prevalence of DN in pediatric-onset diabetes is not uncommon but mainly is subclinical. Poor glycemic control is the main risk factor. Noninvasive screening tests for DN exhibited poor diagnostic sensitivity in the pediatric population.

POS-332 THE ASSOCIATION BETWEEN SERUM INTERLEUKIN-1 BETA AND HEPARIN SULPHATE IN DIABETIC NEPHROPATHY PATIENTS

Inflammation is considered an important mechanism in the development of diabetes mellitus (DM) and persists for a long time before the occurrence of diabetic nephropathy (DN). Many studies have demonstrated that a decrease in the endothelial glycocalyx (EG) is negatively correlated with proteinuria.

The association between EKG abnormalities and the development of microalbuminuria in type 2 diabetes.

Microalbuminuria is associated with both with chronic kidney disease and various cardiovascular abnormalities. Given the common use of electrocardiograms (EKGs) in diagnosing cardiovascular dysfunction, this study is analyzing the relationship between EKG abnormalities and diabetic nephropathy in type 2 diabetes mellitus (DM) patients. The enrollments of this study were from the 10-year follow-up data (2003–2012) of the Diabetes Management through an Integrated Delivery System project. All study subjects underwent at least 1 EKG measurement. The urinary microalbuminuria was recorded annually. The logistic regression model was used to evaluate the association between EKG abnormalities and the occurrence of diabetic nephropathy in type 2 DM patients. The total of 1189 patients with type 2 DM are included in this study and a total of 552 patients had microalbuminuria during a 10-year follow-up. A significantly higher odds ratio of microalbuminuria occurrence (4.85) was found in the patients with premature supraventricular contraction or tachycardia compared to those without EKG abnormalities. The odds ratios of microalbuminuria occurrence were 1.00, 2.43, 2.64, and 2.98, respectively, for patients with insulin resistance in the Q (quartile) 1(as the reference), Q2, Q3, and Q4, respectively. Our findings can serve as a reference for the association between EKG abnormalities and the development of microalbuminuria in type 2 diabetes.

The association between serum interleukin-1 beta and heparin sulphate in diabetic nephropathy patients

Inflammation is considered an important mechanism in the development of diabetes mellitus (DM) and persists for a long time before the occurrence of diabetic nephropathy (DN). Many studies have demonstrated that a decrease in the endothelial glycocalyx (EG) is negatively correlated with proteinuria. To elucidate whether EG damage induced by inflammasomes in DM patients leads to the occurrence of microalbuminuria (MA) and accelerates the progression of DN, this study screened 300 diagnosed DM patients. Finally, 70 type 2 diabetes patients were invited to participate in this study and were divided into two groups: the T2DM group (patients with normal MA and without diabetic retinopathy, n = 35) and the T2DN group (patients with increased MA and diabetic retinopathy, n = 35). Circulating heparin sulphate (HS, EG biomarkers) and interleukin-1 beta (IL-1β, inflammasome biomarkers) of the patients were measured by ELISA. Laboratory data were measured using routine laboratory methods. Patients in the T2DN group had increased serum HS, increased IL-1β, increased CRP, decreased haemoglobin, and increased neutrophils compared to patients in the T2DM group (all P < 0.05). Increased HS and decreased haemoglobin were independently associated with T2DN patients. ROC curves showed that the AUC of HS for the prediction of T2DN was 0.67 (P < 0.05). The combination of HS and haemoglobin yielded a significant increasement in the AUC (0.75, P < 0.001) with optimal sensitivity (71.2%) and specificity (79%). Furthermore, serum IL-1β was positively correlated with HS and was an independent associated factor of HS in the T2DN group. The relationship between HS and IL-1β was not significant in the T2DM group. Our findings surgessed the inflammasome may be associated with and promote damage to the EG during the disease course of DN that manifests as increased MA.

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.

FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose.

Aims Abnormal regulation of autophagy participates in the development of diabetic nephropathy. mTOR is the most common negative regulator of the autophagy signaling pathway. FBW7 constitutes the SCF (Skp1–Cullin1–F-box protein) recognition subunit of E3 ubiquitin ligase, and mTOR is a substrate of FBW7 that can be modified by ubiquitination and be degraded via proteasomes. In this study, we explored the relationship between FBW7 and autophagy and examined the effects of FBW7 on the occurrence of diabetic nephropathy in vitro. Materials and Methods We cultured mesangial cells induced by high glucose in vitro and used rapamycin as a specific mTOR inhibitor, performed FBW7 gene overexpression, and detected the expression of autophagy signal and inflammatory factors by WB, ELISA, RT-PCR, and immunofluorescence. Results High glucose can downregulate the expression of FBW7 and activate mTOR signal, which leads to diminished autophagy in renal mesangial cells, as well as renal inflammatory cytokines and fibrotic factors. RAPA, as a specifically inhibitor of mTOR, can decrease inflammatory cytokines and fibrotic factors by inhibiting mTOR. Moreover, FBW7 gene overexpression can increase autophagy by inhibiting mTOR signal; at the same time, the inflammatory cytokines and fibrotic factors were decreased in mesangial cells. Conclusions FBW7 was decreased in renal mesangial cells induced by high glucose, and FBW7 gene overexpression can increase autophagy by inhibiting mTOR signaling and ameliorate inflammation and fibrosis.

Occurrence of Diabetic Nephropathy After Renal Transplantation Despite Intensive Glycemic Control: An Observational Cohort Study

The kinetics and risk factors of diabetic nephropathy after kidney transplantation remain unclear. This study investigated the posttransplant occurrence of diabetic nephropathy and the contribution of posttransplant glycemic control. We performed a single-center prospective cohort study of 953 renal allograft recipients and 3,458 protocol-specified renal allograft biopsy specimens up to 5 years after transplantation. The effects of pretransplant diabetes and glycemic control (glycated hemoglobin levels) on the posttransplant histology were studied. Before transplantation, diabetes was present in 164 (17.2%) renal allograft recipients, primarily type 2 (n = 146 [89.0%]). Despite intensive glycemic control (glycated hemoglobin 7.00 ± 1.34% [53 ± 14.6 mmol/mol], 6.90 ± 1.22% [52 ± 13.3 mmol/mol], and 7.10 ± 1.13% [54 ± 12.4 mmol/mol], at 1, 2, and 5 years after transplantation), mesangial matrix expansion reached a cumulative incidence of 47.7% by 5 years in the pretransplant diabetes group versus 27.1% in patients without diabetes, corresponding to a hazard ratio of 1.55 (95% CI 1.07-2.26; P = 0.005). Mesangial matrix expansion was not specific for diabetic nephropathy and associated independently with increasing age. Pretransplant diabetes was associated with posttransplant proteinuria but not with estimated glomerular filtration rate, graft failure, or any other structural changes of the glomerular, vascular, or tubulointerstitial renal compartments. The occurrence of diabetic nephropathy was independent of posttransplant glycated hemoglobin levels. Mesangial matrix expansion, an early indicator of diabetic nephropathy, can occur rapidly in patients with diabetes before transplantation, despite intensive glycemic control. Prevention of diabetic nephropathy requires more than pursuing low levels of glycated hemoglobin.

Cardiovascular risk in type 1 diabetes mellitus.

Commonly cardiovascular risk (CVR) is linked to type 2 diabetes mellitus as this type is known to be part of the metabolic syndrome, which includes other cardiovascular factors such as hypertension, dyslipidemia. Inversely, CVR of type 1 diabetes mellitus (T1DM) is currently being debated apart from the occurrence of diabetic nephropathy (DN). For this, we did a review of CVR in patients with T1DM complicated or not with DN. The place of novel non-invasive techniques in screening of subclinical vascular damage is also discussed in this review.

Awareness regarding diabetes control and diabetic nephropathy among Sudanese adults admitted with diabetic foot: a cross-sectional study

Introduction: In Sudan limited data is available regarding the prevalence of diabetes mellitus (DM), its complications as well as patients´ awareness and practice patterns. This study aimed to evaluate the knowledge and practice regarding control of DM and occurrence of diabetic nephropathy (DN), among Sudanese diabetics with diabetic foot.

Association between (AC)n dinucleotide repeat polymorphism at the 5′-end of the aldose reductase gene and diabetic nephropathy: a meta-analysis

Association between the (AC)(n) dinucleotide repeat polymorphism at the 5'-end of the aldose reductase gene and the occurrence of diabetic nephropathy was conducted. We examined eight studies consisting of ten Caucasian type 1 diabetes mellitus case-control comparisons and eight studies consisting of nine type 2 diabetes mellitus case-control comparisons, which were based on our inclusion criterion and available in the literature. The meta-analysis demonstrated a large heterogeneity among the studies on the type 1 diabetic subjects and a significant association was observed between the (AC)(n) dinucleotide repeat polymorphism at the 5'-end of the aldose reductase gene and diabetic nephropathy. The Z-2 allele appeared to be a genetic risk factor for susceptibility to diabetic nephropathy with a random effects odds ratio (OR) of 1.40 (95% confidence interval, CI (1.07, 1.84)). The Z+2 allele showed a protective effect on diabetic nephropathy with a random effects OR of 0.77 (95% CI (0.65, 0.91)). The meta-analysis, however, showed no association between the genetic polymorphism and diabetic nephropathy in type 2 diabetic subjects. Neither the risk Z-2 allele nor the protective Z+2 allele in type 1 diabetic subjects appeared to have an effect on nephropathy in type 2 diabetic subjects, while their fixed effects OR was 1.09 (95% CI (0.96, 1.22)) and 0.88 (95% CI (0.67, 1.15)) respectively. The current meta-analysis demonstrated a correlation between the (AC)(n) dinucleotide repeat polymorphism and the occurrence of diabetic nephropathy in Caucasian type 1 diabetic subjects in contrast to type 2 diabetic subject population in which such an association could not be demonstrated.

Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: An Egyptian study

Background The development and progression of diabetic microvascular complications including nephropathy are related to the degree of glycemic control and oxidative stress and may be influenced by genetic factors. The aim of the present study was to investigate the association between haptoglobin (Hp) gene polymorphism and the occurrence of diabetic nephropathy in patients with type 2 diabetes mellitus and to find a possible link between Hp phenotypes and the inflammatory parameters; serum C-reactive protein (CRP), interleukin- 6 (IL-6), and Hp. Methods The study included 60 normotensive type 2 diabetic patients (> 5 years duration) categorized into three equal groups (normo-, micro-, and macroalbuminuric), according to urinary albumin excretion (UAE). In addition, 20 age- and sex-matched individuals were selected to serve as a control group. Serum CRP, IL-6, and Hp concentrations were measured and Hp phenotyping was conducted using polyacrylamide gel electrophoresis. Results The frequency of Hp phenotype 1-1 (Hp 1-1) in diabetic patients with normoalbuminuria was 7/20 (35%) as compared with 1/20 (5%) in diabetics with macroalbuminuria ( p = 0.02). However, the frequency of Hp 2-2 was greater in diabetics with macroalbuminuria (12/20, 60%) than in those with normoalbuminuria or controls (5/20, 25%; p = 0.03). Patients with diabetic nephropathy (micro- or macroalbuminuria) had higher levels of serum CRP, IL-6, and Hp than those without nephropathy (normoalbuminuria). Serum Hp levels in type 2 diabetics were higher in Hp phenotype 2-2 than in Hp 1-1; however, serum CRP and IL-6 levels did not differ significantly between Hp phenotype groups. Moreover, there were significant positive correlations between UAE and serum levels of CRP, IL-6, and Hp in diabetic patients. Conclusions Hp phenotype 2-2 is considered to be a major susceptibility gene for the development of nephropathy in type 2 diabetic patients. In addition, the significant association between inflammatory parameters and UAE indicates that inflammation may be a pathogenic mechanism of renal injury in type 2 diabetics. Moreover, serum IL-6 and Hp may be good prognostic factors for the development of nephropathy in the course of diabetes mellitus. Future research on the use of anti-inflammatory therapy may result in a new approach to the treatment and prevention of diabetic nephropathy.

Role of systolic blood pressure in determining prognosis of hemodialyzed patients

The role of blood pressure in determining the prognosis of hemodialyzed patients was examined in 195 patients who were introduced to hemodialysis. The relationship between blood pressure and survival or death was analyzed. In 46 patients who died within 3 years after the introduction of hemodialysis (nonsurvivors), the age was higher (61 ± 2 years v 50 ± 1 years), the occurrence of diabetic nephropathy was higher, and the systolic pressure was higher in both the introduction (178 ± 4 mm Hg v 167 ± 2 mm Hg) and maintenance (165 ± 4 mm Hg v 147 ± 2 mm Hg) phases than in 132 patients who survived more than 3 years (survivors). On the other hand, there were no significant differences in diastolic pressure during either phase between the two groups of patients. When diabetic nephropathy was excluded, only systolic pressure during the maintenance phase was higher in the nonsurvivors than in the survivors. Therefore, based on systolic pressure during the maintenance phase, patients were divided into two groups, the HT group (≥160 mm Hg) and the NT group (<160 mm Hg), and cumulative survival rates were compared. Whether all patients, only those patients with diabetic nephropathy, or only those patients without diabetic nephropathy were examined, the survival rate was higher in the NT group than in the HT group. Furthermore, patients were divided into the following three groups based on the changes in systolic pressure between the introduction of hemodialysis and the maintenance phase: the HT-NT group, whose systolic pressure was higher than 160 mm Hg during the introduction phase but decreased to below 160 mm Hg during the maintenance phase; the HT-HT group, whose pressure was higher than 160 mm Hg during both phases; and the NT-NT group, whose pressure was below 160 mm Hg during both phases. The cumulative survival rate in the HT-NT group was significantly higher than in the HT-HT group, being as high as that in the NT-NT group. Our results suggest that systolic pressure during the maintenance phase, corrected by hemodialysis, plays an important role in determining the prognosis of hemdialyzed patients.

Is increased erythrocyte sodium-lithium countertransport a useful marker for diabetic nephropathy?

Genetic predisposition to essential hypertension has been proposed as a risk factor for the development of diabetic nephropathy in type 1 (insulin-dependent) diabetes mellitus. An increased sodium-lithium countertransport activity (NaLiCT) has been suggested as a genetic marker for essential hypertension. We therefore evaluated NaLiCT in diabetic patients with (N = 39) or without (N = 23) diabetic nephropathy (DNP), patients with non-diabetic renal diseases (N = 42) and in healthy controls (N = 24). The NaLiCT was elevated in both diabetic patient groups compared to healthy controls (median 244; range 134 to 390 mumol.liter cells-1.hr-1), but was not different in patients with DNP (median 314; range 162 to 676), without DNP (median 325; range 189 to 627) and patients with non-diabetic renal disease (median 300; range 142 to 655). The genetic predisposition to DNP is illustrated by the fact that diabetic sibs of probands with DNP showed a higher occurrence of DNP than diabetic sibs of patients without DNP. We analyzed whether familial DNP clustered with an increased NaLiCT. The NaLiCT in sibs concordant for the presence of DNP (N = 10; median 307; range 217 to 428 mumol.liter cells-1.hr-1) was not significantly different from that in sibs concordant for absence of DNP (N = 15; median 279; range 189 to 442). We conclude that erythrocyte sodium-lithium countertransport activity cannot be used as a marker to identify patients at risk for the development of diabetic nephropathy.

Pancreatic transplantation.

In the last few years there has been considerable improvement in results with pancreatic transplantation. Several centers now report a 1-year graft survival rate of 50%-60%. Patients with well-functioning grafts become insulin independent and have normal or near normal fasting ans post-prandial glucose levels and normal glycosylated hemoglobin values. The glucose tolerance as measured by oral and intravenous glucose tolerance tests is normal in 50%-80% of the patients but subnormal in the others. One important reason for subnormal glucose tolerance is medication with cyclosporin and prednisolone. In most cases an improvement in neuropathy is found and retinopathy seems to be stabilized. Preliminary data indicate that the provision of a pancreatic graft prevents the occurrence of diabetic nephropathy in a simultaneously or previously transplanted kidney.

Diabetes Mellitus with Immune Complex Glomerulonephritis

The present study describes 3 patients with the simultaneous occurrence of diabetic nephropathy and immune-complex mediated glomerulonephritis. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal manifestation included proteinuria and hematuria which were preceded by or co-existent with an infectious process. Renal histology showed the characteristic change of diabetic nephropathy along with those of immune complex glomerulonephritis. Immunofluorescence studies showed a linear pattern with a superimposed granular pattern of IgG and C3 deposits. Renal function and urinary findings improved in the 2 patients who were followed up.

Editorial: Aspirin and diabetic retinopathy.

Kwaan and his co-workers, 1 having previously observed a diabetic patient with disseminated intravascular coagulation consequent to increased platelet aggregation, had studied 87 other mature-onset diabetic subjects of whom 77 exhibited platelet aggregation-enhancing activity. The degree of such activity did not correlate with plasma levels of lipoproteins, triglycerides, free fatty acids, the free fatty acids to albumin molar ratio, or such complications as occlusive diseases of large arteries and neuropathy. However, there was distinct correlation with the occurrence of diabetic nephropathy, retinopathy, and the duration of the disease. More recently, as a follow-up to their earlier observations, the same group of authors 2 conducted further studies of the correlation of platelet aggregation-enhancing activity with diabetic retinopathy. The method for measuring the degree of activity permitted expression of an aggregation index (AI). In diabetic patients without retinopathy or with early retinopathy, a percentage increase of AI was lacking or slight, and