Nephropathy In Type Research Articles

DIABETES & MICROALBUMINURIA- A MULTI-SYSTEM DISEASE

In diabetic patients, the presence of microalbumin in the urine is perhaps the most significant early signal for the onset of systemic vasculopathy and associated target organ damage viz., brain, heart, and kidneys1. Microalbuminuria is considered to be a predictor of the development of overt diabetic nephropathy in type 1 and 2 diabetes2. Diabetic patients are at considerable risk of either having or developing the renal disease and/or related cardiovascular diseases, usually starting with microalbuminuria often related to insulin resistance (or metabolic syndrome)1. Thus, microalbuminuria is a relatively common accompaniment of metabolic syndrome and the foremost predictor of renal disease as well as cardiovascular disease3,4. Hypertension and microalbuminuria often coexist in diabetic patients, and reducing blood pressure reduces microalbuminuria in type 1 diabetes2. However, the relationship between hypertension and microalbuminuria in diabetes is complex. Furthermore, microalbuminuria is also associated with other inflammatory states, including rheumatoid arthritis and inflammatory bowel disease. Also, male sex and hormone replacement therapy in women seems to increase the susceptibility of a person to microalbuminuria, although the basis for this is yet not clear2.

Serum CXCL16 in Relation to Diabetic Nephropathy in Type 2 Diabetes Egyptian Patients

Abstract Background: CXC chemokine ligand 16 (CXCL16) is both an oxidized low density lipoprotein receptor (ox-LDL) and a chemokine with a potential role in the pathogenesis of Diabetic Nephropathy (DN). Aim of Study: The aim of this work is to evaluate the relationship between serum CXCL16 levels and (DN) in type 2 Egyptian diabetic patients. Methods: This case-controlled study was conducted on 80 T2DM patients (group A1: 24 patients with normoalbu-minuria; group A2: 28 patients with microalbuminuria, and group A3: 28 patients with macroalbuminuria) and 20 age-and sex-matched healthy controls. All were subjected to a complete clinical evaluation and laboratory investigations which included quantitative measurements of urinary albu-min/creatinine ratio and serum CXCL16 levels by enzyme-linked immunosorbent assays. Results: Serum CXCL16 levels were significantly higher in all T2DM groups compared with healthy controls. There was a positive correlation between CXCL16, creatinine and ACR (r=0.48, p:0.039 and r=0.53, p:0.019, respectively), whereas it was significantly negatively associated to eGFR (r=–0.46, p:0.05). Regression analysis indicated that CXCL16 levels were continued significantly correlated with creatinine, eGFR and ACR (p:<0.05, for all). Conclusion: Egyptian type 2 DM patients are characterized by increased serum CXCL16 levels. There was a statistically significant correlation between CXCL16 levels and conven-tional renal markers reflecting disease progression.

Methylenetetrahydrofolate reductase genetic polymorphism and the risk of diabetic nephropathy in type 2 diabetic patients.

Background:As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility.Materials and method:Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios (ORs) with 95% confidence intervals (95% CIs).Results:The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic (OR = 1.64, 95% CI = 1.34–2.00, P < .001), dominant (OR = 1.85, 95% CI = 1.40–2.46, P < .001), codominant (heterozygote: OR = 1.67, 95% CI = 1.27–2.21, P < .001; homozygote: OR = 2.55, 95% CI = 1.82–3.57, P < .001), and recessive (OR = 1.89, 95% CI = 1.50–2.38, P < .001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: OR = 2.06, 95% CI = 1.58–2.67, P < .001; dominant: OR = 2.52, 95% CI = 1.73–3.69, P < .001; codominant: OR = 3.78, 95% CI = 2.50–5.70, P < .001; recessive: OR = 2.41, 95% CI = 1.96–2.97, P < .001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations.Conclusion:The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.

Relationship between triglyceride glucose index, retinopathy and nephropathy in Type 2 diabetes.

AimsTo explore the relationship between TyG index, diabetic retinopathy (DR) and nephropathy.MethodsThis was a cross‐sectional observational study that examined 1413 subjects with type 2 diabetes (both known and newly diagnosed). Subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography) and nephropathy (defined as urinary albumin excretion ≥ 30 mg/24 h). The TyG index was calculated as ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2) and stratified into 4 quartiles (TyG‐Q). The baseline characteristics of the study population in the four TyG‐Q (Q1 (≤7.3) n = 349, Q2 (>7.3 to ≤ 7.5) n = 358, Q3 (>7.5 to ≤ 8.0) n = 354, and Q4 (>8.0) n = 352) were analysed. Variables associated with the presence of DR and nephropathy were assessed using a stepwise binary logistic regression analysis.ResultsThe presence of DR was associated with higher TyG index (OR = 1.453, P =.001) and longer duration of diabetes (OR = 1.085, P < .001). The presence of nephropathy was associated with a higher TyG index (OR = 1.703, P < .001), greater age (OR = 1.031, P < .001), use of insulin (OR = 1.842, P = .033), higher systolic BP (OR = 1.015, P < .001), and the presence of DR (OR = 3.052, P < .001). Higher TyG‐Q correlated with the severity of DR (P = .024), presence of nephropathy (P = .001), age (P < .001) and diastolic blood pressure (P = .006).ConclusionsA higher TyG index is associated with the presence of retinopathy and nephropathy in individuals with diabetes and could be used for monitoring metabolic status in clinical settings.

Jaceosidin Ameliorates Insulin Resistance and Kidney Dysfunction by Enhancing Insulin Receptor Signaling and the Antioxidant Defense System in Type 2 Diabetic Mice.

Emerging evidence has shown that flavonoids extracted from Artemisia have beneficial effects on metabolic disorders. However, whether and how jaceosidin ameliorates insulin resistance and diabetic nephropathy in type 2 diabetes mellitus is largely unknown. For 8 weeks, db/db diabetic mice were fed with or without jaceosidin. Oral jaceosidin supplementation reduced fasting blood glucose levels and insulin resistance through the upregulation of insulin receptor downstream pathways in the liver and skeletal muscles. While jaceosidin did not noticeably alter kidney filtration function, this dietary intervention contributed to attenuating the accumulation of advanced glycation end products in diabetic kidneys. The levels of VEGF-a (vascular endothelial growth factor-a) proteins in the diabetic kidneys were markedly diminished by jaceosidin treatments, which increased the expression and activity of Cu (copper) and Zn-SOD (zinc-superoxide dismutase). Therefore, it is suggested that jaceosidin supplementation elicits antidiabetic effects and treats diabetic nephropathy by augmenting insulin signaling, suppressing fibrosis, and enhancing antioxidant activity.

Serum lipid profile and Nephropathy in type 2 diabetes patients: A comparative study

Background: The prevalence of hypercholesterolemia (TC>200md/dl) alone, as reported in numerous studies across India, has varied from about 20% to 35%. However, what is more important is the pattern of dyslipidemia. When compared with the western populations, Indians and migrant Asian Indians tend to have higher triglyceride levels and lower HDL-C levels. Subjects and Methods: This was a comparative study conducted among 120 cases. A pre-structural proforma will be used to collect baseline date detailed clinical history with clinical examination and relevant investigation will be done on participating individuals. Results: There was correlation between lipid levels and duration of diabetes for all lipid fractions which were significant. Conclusion: Correlation coefficient between nephropathy and lipid profile was found to be significant.

Serum Klotho protein level in type 2 diabetic patients depending on the renal function

The study aimed to assess serum Klotho protein level in type 2 diabetic patients depending on kidney function.&#x0D; Methods. This observational study included 72 patients with diabetes mellitus (DM) and 26 patients with acute coronary syndrome. The control group consisted of 20 healthy subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR), the diabetics were divided into the following groups: group I included the patients with normal GFR and without albuminuria (n = 25); group ІІ consisted the patients with normal GFR and albuminuria (n = 23); group III – the patients with reduced GFR and albuminuria (n = 24) and group ІV included the patients with acute coronary syndrome (n = 26).&#x0D; The GFR was calculated using the CKD EPI formula (KDIGO 2012). The concentration of Klotho protein was determined by enzyme-linked immunosorbent assay.&#x0D; Results. The development of diabetic nephropathy in type 2 diabetic patients accompanied by a significant decrease of soluble Klotho compared with the controls and the patients of the1-st group. The level of Klotho protein in the group of patients with albuminuria decreased to (490.66 ± 58.76) pg/ml (p &lt;0.05). The lowest concentration of Klotho (443.58 ± 46.92) pg/ml was found in the advanced stages of diabetic nephropathy, namely in patients with albuminuria and impaired renal function. Moreover, a significantly decreased serum Klotho was observed in acute coronary syndrome group in comparison with the control group (p &lt;0.05). There were inverse correlations of Klotho concentration with urinary albumin and blood creatinine levels and a direct correlation between Klotho and GFR.&#x0D; Conclusions. The obtained data indicated the key role of Klotho protein in the formation of renal pathology in type 2 diabetes and the feasibility of practical use of Klotho determination as an early diagnostic marker of renal disorders and cardiovascular risk assessment. The strategies improving Klotho production may be useful in the reduction of both renal and vascular lesions progression in type 2 diabetic patients.

\u03b52 allele and \u03b52-involved genotypes (\u03b52/\u03b52, \u03b52/\u03b53, and \u03b52/\u03b54) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: a meta-analysis

BackgroundDiabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive.MethodsAn up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database.ResultsA total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ε2 vs. ε3 was 1.89 (95% confidence intervals [95% CI]: 1.49–2.38, P < 0.0001). With regard to APOE genotypes, ε2/ε2, ε2/ε3, and ε2/ε4 increased the risk of T2DN (ε2/ε2 vs. ε3/ε3: OR = 2.32, 95% CI: 1.52–3.56, P = 0.0001; ε2/ε3 vs. ε3/ε3: OR = 1.97, 95% CI: 1.50–2.59, P<0.0001; ε2/ε4 vs. ε3/ε3: OR = 1.69, 95% CI: 1.18–2.44, P = 0.0046).ConclusionsThis meta-analysis found that the APOE ε2 allele and the ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) are the risk factors of T2DN.

2151-PUB: Association of Homocysteine with Early Nephropathy in Patients with Type 2 Diabetes

Early predication and intervention of diabetic nephropathy is increasingly imperative. Hyperhomocysteinemia is common and chronically induces arteriolar thickening, and tubulointerstitial and podocyte injury, therefore, could play a causative role in early renal injury in the kidney in type 2 diabetes. In this study, we for the first time investigated the relation of plasma total homocysteine concentration to early nephropathy in type 2 diabetes. We enrolled 183 type 2 diabetic patients in a cross-sectional study. Early diabetic nephropathy status was diagnosed by presence of microalbuminuria. Plasma total homocysteine levels were measured using fluorescence polarization immunoassay. Variables for diabetic nephropathy were obtained from fasting blood samples and interviewer- questionnaire. We found that plasma total homocysteine concentrations were elevated in subjects with early diabetic nephropathy than without (13.3±2.9)µmol/l vs. (8.5 ± 1.4)μmol/l, p &amp;lt; 0.01). The association of homocysteine with the diabetic nephropathy was independent of major traditional risk factors for diabetic nephropathy (duration of diabetes, HbA1c, and blood pressure) and determinants of higher homocysteine concentration (age, sex, serum folate and vitamin B12, Biguanide use, and serum cystatin or creatinine levels,) (OR: 1.36 (1.08-1.74), p &amp;lt; 0.05). Furthermore, per increase of 5.0 μmol/l plasma homocysteine was related to early nephropathy (OR: 1.15 (1.04-1.29), p &amp;lt; 0.05), after controlling for per unit increase of other factors: per 5 year increase of duration of diabetes, per 1% increase of HbA1c, per 10 nmol/l increase of serum folate, per 100 pmol/l increase of serum B12, per 0.1 mg/L increase of serum cystatin or per 10 μmol/l increase of creatinine, and per 10 or 5 mmHg increase of systolic or diastolic blood pressure. We concluded that plasma total homocysteine concentration was independently associated with occurrence of early diabetic nephropathy. Future prospective studies are warranted. Disclosure J. Li: None. Q. Lv: None. H. Lu: None. H. Zhang: None. J. Zhou: None. Funding National Natural Science Foundation of China (81070655); Jiangsu Provincial Natural Science Foundation of China (BK2009441)

1139-P: Remogliflozin (SGLT2 Inhibitor) Significantly Reduces Albuminuria and Delays the Progression of Nephropathy in Type 2 Diabetes Mellitus Patients

Remogliflozin is a novel SGLT2 inhibitor approved and available in India for the treatment of type 2 diabetes mellitus patients. This study was designed to determine the effect of Remogliflozin on diabetic nephropathy patients compared with placebo on the reduction of the albuminuria. We conducted a 24 week, double-blind, randomized, parallel-group study with 94 type 2 diabetics subjects with diabetic nephropathy (micro albuminuria range from 30 to 300) and HbA1c of 7.5 - 9.3%. Subjects were randomized to Remogliflozin (100 mg bid) and placebo with 1000 mg metformin OD. The primary end point was change in HbA1C from baseline, with secondary end points including change in fasting plasma glucose (FPG), body weight, and change in albuminuria. Safety and tolerability were also characterized. Result: As shown in Table in image. Conclusion: Result of our study revealed that Remogliflozin significantly reduced albuminuria (p value &amp;lt;0.001) in type 2 diabetes mellitus patients with delay in progression of diabetic nephropathy as compared to placebo. Disclosure V.K. Gupta: None.

475-P: Renal Loss of mTORC2 Is Associated with Improved Diabetic Nephropathy in Type 1 Diabetes

One of the major pathological features of early stage diabetic nephropathy (DN) is tubulointerstitial fibrosis on renal proximal tubular cells (RPTCs), which eventually progresses to fibrosis without proper renal function. However, little is known about the factors regulating these processes. Here, we show that mTOR complex 1 and 2 specifically regulate metabolic control processes of type-1 diabetes in kidney. Using conditional mouse genetic approaches to disable subunits of mTORC1 (Rictor) and mTORC2 (Raptor), respectively or both in PRTCs (Pax8cre), we showed that mice lacking Rictor or Raptor/Rictor develop improved renal pathologies in STZ induced type-1 diabetic model, including low levels of proteinuria, reduced matrix protein accumulation/matrix expansion and tubulointerstitial inflammation. However, the mice lacking Raptor alone were still largely susceptible to STZ toxicity. Meanwhile, Nox4 and oxidative stress levels were significantly reduced in RictorcKO diabetic animal, but to a lesser extent in RaptorcKO diabetic mice. Transcriptome analysis of kidney cortex identified unique pathways that play roles in mTORC/Nox4 pathway during type-1 diabetic pathogenesis, including autophagy, metabolism of lipids and fatty acid regulation. These pathways were largely unchanged in RictorcKO mice when they were exposed to STZ induction. Functionally, losing mTORC2 complex resulted in reduced cellular death and oxidative stress levels, and a profound perturbation of the endocytic machinery. Finally, we found that the treatment with pp242, the mTORC1/2 dual inhibitor, greatly ameliorated the renal pathology in OVE26 mice, a spontaneous type-1 diabetic model. Collectively, our findings highlight a novel mTOR-dependent regulatory network for maintaining metabolic homeostasis in RPTCs during the pathogenesis of DN, and further validates the relevance of simultaneously targeting Nox4 and mTORC2 as a potential early therapeutic option for treating DN. Disclosure C. Chang: None. Z. Zhang: None. K. Xu: None. M. Bhat: None. Q. Shi: None. Funding JDRF (1-FAC-2019-858-A-N)

Urinary Retinol Binding Protein (RBP) Level as an early Biomarker of Diabetic Nephropathy in type 2 Diabetic Patients

Urinary Retinol Binding Protein (RBP) Level as an early Biomarker of Diabetic Nephropathy in type 2 Diabetic Patients

MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score &amp;gt; 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p &amp;lt; 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p &amp;lt; 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p &amp;lt; 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p&amp;lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p&amp;lt;0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p&amp;lt;0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p&amp;lt;0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p&amp;lt;0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.

Involvement of Peroxisome Proliferator-Activated Receptor-a and g in Apelin Action on the Kidney in Type 2 Diabetic Rat Model

AbstractBackground: Apelin is an adipokine that revealed numerousrenoprotective actions; however, its effect in diabeticnephropathy is controversial.Aim of Study: The objectives of the current study wereto determine the action of apelin administration on nephropathyin type 2 diabetic rat model and to clarify its possible mechanismsand if PPARs activation is involved in these mechanisms.Material and Methods: Thirty adult male wistar rats weresubdivided into control, diabetic and diabetic-apelin treatedrats. Type 2 diabetes was induced via a high-fat diet togetherwith a single low-dose of streptozotocin. Apelin was injectedintraperitoneally for 10 weeks. Serum glucose, insulin andlipid profile were estimated. Homeostatic Model Assessmentfor Insulin Resistance (HOMA-IR) was calculated. Renalfunctions were evaluated by serum urea and creatinine, urinaryalbumin excretion, urinary N-acetyl-beta-D-glucosaminidase(NAG) activity and histopathological inspection. Renal tissuehomogenate was assessed for Superoxide Dismutase (SOD),Malondialdehyde (MDA), Nitric Oxide (NO) content andPPAR-a and PPAR-g gene expression.Results: Apelin administration to diabetic rats improvedhyperglycemia, insulin resistance, dyslipidemia, renal functionparameters and pathological lesions in the kidney that resultedfrom induction of diabetes. It elevates renal SOD and NO,decreased MDA and increased PPAR-a and g gene expressionin comparison to diabetic rats.Conclusions: Apelin administration to diabetic rats improvedinsulin resistance, hyperglycemia, dyslipidemia andrenal functions which may be partially via its antioxidantproperties and NO dependent mechanism that struggled theharmful properties of diabetes on the kidney. Besides, apelininduced upregulation of both PPARa/g genes expression thatcould be involved in the renoprotective effect of apelin. Moreinvestigations for the mechanism by which apelin acts onPPARa/g are recommended.

Potential application of nanoemulsified garlic oil blend in mitigating the progression of type 2 diabetes-mediated nephropathy in Wistar rats.

The renoprotective potential of nanoemulsified garlic oil blend (GNE) in alleviating the progressive stages of hyperlipidemia-mediated diabetic nephropathy was examined. The study was carried out in high fat-fed, streptozotocin-induced type 2 diabetic Wistar rats for five months. The diabetic rats showed a significant increase of area under the curve in OGTT (p < 0.01) and IPITT (p < 0.01), increased urinary albumin (p < 0.01), urinary microprotein (p < 0.001), total cholesterol (p < 0.01), triglycerides (p < 0.001) and LDL cholesterol (p < 0.001), with decreased serum albumin (p < 0.01), serum protein (p < 0.001) and HDL-cholesterol levels (p < 0.05) than the control rats. The histopathological analysis evidenced mesangial expansion and hypercellularity at the end of the first and third month, and glomerulosclerosis and tubular atrophy at the end of the fifth month in diabetic rats. Moreover, on disease progression, increase in urinary podocalyxin, NGAL and CD36 was observed, and the renal mRNA and protein expression of podocalyxin decreased significantly with a concomitant increase in NGAL and CD36 expression from first till fifth month end. The treatment with GNE (20mg/kg) significantly ameliorated the serum albumin (p < 0.001) and urine albumin (p < 0.01) from the end of the third month with significant attenuation in the lipid profile than GO (20mg/kg) or Ator (8mg/kg). Moreover, GNE reverted the histopathological alterations and attenuated the aberrant mRNA, protein expression and urinary excretion level of renal CD36, podocalyxin and NGAL in diabetic rats from an early stage of disease till the end of the study period. This study demonstrated the enhanced efficacy of GO in nanoemulsified form in mitigating the progression of nephropathy in type 2 diabetic rats.

Association of Pentraxin 3 rs2305619 (A/G) gene polymorphism and its serum level with the risk of nephropathy in type II diabetic patients

Diabetic nephropathy (DN) is one the microvascular diabetic complications. Pentraxin 3 (PTX3) belongs to the acute-phase reactants proteins and variation in the serum levels of PTX3 are accompanied with DN. This work was done on 180 subjects which included 3 groups: 60 patients of T2DM with nephropathy, 60 patients of T2DM without nephropathy and 60 age and sex matched healthy controls. Serum Pentraxin3 was measured by ELISA and Pentraxin 3 rs2305619 (A/G) variation was evaluated by using the TaqMan allelic discrimination assay. Resultsshowed a significant differences between the three groups regarding serum Pentraxin3 level and Pentraxin 3 rs2305619 (A/G) genotypes distribution with elevated serum Pentraxin3 level and increased GG genotype in patients with DN, increased AG genotype in patients without DN and elevated AA genotype in controls. GG genotypes of Pentraxin 3 rs2305619 (A/G) might be a risk factor for nephropathy in T2DM. ConclusionGG genotypes of Pentraxin3 rs2305619 gene polymorphism and high serum Pentraxin 3 level might be considered a genetic risk factor for nephropathy in T2DM.

TNF-α pathway and T-cell immunity are activated early during the development of diabetic nephropathy in Type II Diabetes Mellitus

Aim of the present study was to investigate the possible involvement of TNF-α signaling pathway and T-lymphocyte activation in DN.Eighty-two diabetic patients [39 male, age 69.5(56–78)years] were divided into three groups, according to Albumin/Creatinine ratio (ACR) levels, Group I (ACR < 30 μg/mg), Group II (ACR 30–300 μg/mg), Group III (ACR > 300 μg/mg). Urinary Tumor Necrosis Factor-α (TNF-α), and serum TNF-α, ΤNF-receptor 1 (TNFR1), TNFR2, B7–1, CD28, Cytoxic T-Lymphocyte-Associated protein-4 (CTLA4), were estimated.There were significant differences between Groups I, II, III regarding the concentration of urinary TNF-α (p < .001), serum TNFR1 (p < .001), serum TNFR2(p < .001), CTLA4 (p < .001) and CD28(p = .034). In multivariate analysis, independent parameters correlated with ACR were serum TNFR1 (p = .003), TNFR2 (p = .012) and urinary TNF-α (p = .015) levels. There was a significant correlation between markers of T-cell activation and TNF-α signaling pathway activation.Activation of TNF-α signaling pathway and T-lymphocytes seem to synergize and participate in the development of DN in type II DM.

The Role of Hyperglycemia and Coexisting Hypertension in The Development of Diabetic Nephropathy in Type II Diabetes Mellitus

Background: diabetic nephropathy (D.N) is an important cause of morbidity and mortality and now the most common cause of end stage renal failure ESRF worldwide but especially in developed countries.Objectives: the aim of the study is to know the role of hyperglycemia and co-existing hypertension HTN in the development of D.N. among patients with type II Diabetes Mellitus(DM).Patients and Method: one hundred and twenty one diabetic patients were enrolled in a prospective observational study. Sixty six patients were females and fifty five were males. Besides full history and physical examination data were collected according to a format. At the end, these data were collected and analyzed statistically.Results: the average age was (54± 2.1) year , female to male ratio 66 to 55 (1.2:1) the number of patients with hyperglycemia was 90. Average random blood sugar R.B.S was 259± 1.6 mg/dL. number of patients with hypertension was 71, the average of systolic blood pressure BP was 158± 6.1mmHg and diastolic was 10.2±1.1, the average duration of D.M. was (10.5± 4.2) year, the average of glycosylated hemoglobin HbA1c was 9.8± 2.1. the number of patients with D.N was 77.Conclusion: the data showed that hyperglycemia and co-existing of hypertension were major risk factors in the development of D.N. among patient with type II D.M.

FETUIN A AS AN EARLY MARKER OF DIABETIC NEPHROPATHY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Background: Fetuin-A is a liver-derived plasma protein, mediates the formation and stabilization of calciprotein particles formation, ensures mineral solubilization, thus preventing pathological calcification, also it promotes insulin resistance. Objective: To study the role of fetuin A as a marker for early diabetic nephropathy in type 2 diabetes mellitus. Subjects and Methods: Cross sectional study including 30 diabetic patients without microalbuminuria (group I), 30 diabetic patients with microalbuminuria (Group II) and age and sex matched 30 healthy subjects served as a control group. All patients and control subjects were thoroughly examined clinically. Fasting and post prandial blood sugar, HbA1c, renal function tests, lipid profile, creatinine clearance, albumin/creatinine ratio and serum fetuin A by ELISA were investigated. Results: Serum Fetuin A increased in diabetic nephropathy patients without microabuminuria compared to those with microabuminuria. Significant negative correlation was found between serum Fetuin A and albumin/creatinine ratio in diabetic patients with and without microalbuminuria. Cut off value of serum fetuin A was >294.2 ug/dl with sensitivity of 93.3% ,specificity 93% , positive predictive value 92.7%, negative predictive value 93.8% and diagnostic accuracy 91.6%. Conclusion: Serum fetuin A can be used as an early marker for diabetic nephropathy before development of microalbuminuria in patients with type 2 diabetes mellitus.

TLR4 Polymorphisms (896A>G and 1196C>T) Affect the Predisposition to Diabetic Nephropathy in Type 2 Diabetes Mellitus.

PurposeType 2 diabetes mellitus (T2DM) is a disease with a steadily increasing incidence throughout the world. Some molecules regulating the innate immune responses such as toll-like receptor 4 (TLR4) have shown to be involved in late diabetic complications. This study aimed to investigate the association of TLR4 gene polymorphisms with clinicopathological aspects of T2DM in the Iranian population.Patients and MethodsTwo TLR4 896A>G and 1196C>T polymorphisms were assessed in 100 T2DM patients and 100 healthy controls using sequence-specific primers PCR. Demographic, anthropometric, and biochemical parameters were obtained from the participants.ResultsAfter logistic regression, in 1196C>T, a significant association was shown between diabetic nephropathy (DN) and CT genotype (P= 0.04, OR= 4.35, CI= (1.04–18.1)). TG level has increased significantly in both T2DM and control subjects with CT genotype (P= 0.027, OR= 1.005, 95% CI= (1.001–1.01)). For 896A>G variant, a significant association was also detected between AG genotype and increased oral glucose tolerance test (OGTT) level (P= 0.048, OR= 1.003, 95% CI= (1.00–1.005)).ConclusionAlthough minor alleles of 1196C>T and 896A>G variants have not directly been associated with type 2 diabetes, by involving in the dysregulation of serum TG and blood sugar levels, they might increase the risk of DN.