Diabetic Nephropathy Complications Research Articles

Constructing the biomolecular networks associated with diabetic nephropathy and dissecting the effects of biomolecule variation underlying pathogenesis.

Diabetic nephropathy (DN) is a common and serious complication of diabetes, contributing significantly to patient mortality. Complication of DN (CDN) ranks as the second leading cause of end-stage renal disease globally. To address this, understanding the genetic regulation underlying DN is crucial for personalized treatment strategies. In this study, we identified genes and lncRNAs associated with diabetes and diabetic nephropathy constructing a DN-related lncRNA-mRNA network (DNLMN). This network, characterized by scale-free biomolecular properties, generated through the study of topological properties, elucidates key regulatory interactions. Enrichment analysis of important network modules revealed critical biological processes and pathways involved in DN pathogenesis. In the second step, we investigated the differential expression and co-expression of hub nodes in diseased and normal individuals, identifying lncRNA-mRNA relationships implicated in disease regulation. Finally, we gathered DN-related single nucleotide polymorphisms (SNPs) and lncRNAs from the LincSNP 3.0 database. The DNLMN encompasses SNP-associated lncRNAs, and transcription factors (TFs) linked to differentially expressed lncRNAs between diseased and normal samples. These results underscore the significance of biomolecular networks in disease progression and highlighting the role of biomolecular variability contributes to personalized disease phenotyping and treatment.

Management of the Diabetic Microalbuminuria with Ayurvedic intervention- A Case Report

Background: One of the most prevalent side effects of diabetes, diabetic nephropathy causes Hypoalbuminemia, chronic kidney damage and end-stage renal failure worldwide. This study was performed for the effectiveness of the Ayurvedic treatment in the patient presented with the complications of Diabetic Microalbuminuria with special reference of Kaphaja Shotha. A 67-year-old, male patient consulted to the Ayurveda hospital with generalized body swelling, difficulty in breathing on the rest, Fatigue for 2 years, following secondary prevention for two years. Design: Single Case report. Materials and Methods: In this prospective case study, conducted on a subject experiencing edema as a complication of diabetic nephropathy for two years, the individual was admitted to the Indoor Patient Department of Medicine. Over a period of three months, the subject was assessed every 15 days. The intervention involved the administration of oral medications including mainly Gokshuradi guggulu, Punarnavadi guggulu, Hingwastak Churna, Triphala Churna, Syrup Neeri KFT, and Gomutra Haritaki. The edema reduced progressively, and there was an alleviation of associated symptoms such as difficulty in breathing and fatigue. Additionally, the subject showed improvement in renal function parameters and reported an enhanced sense of well-being. Results: Laboratory investigation showed protein in urine and hypoalbuminemia with normal blood urea and S. Creatinine., which was corrected after treatment, increased serum albumin from 1.9 (g/dl) to 3.9(g/dl) and serum globulin from 1.7(g/dl) to 2.7 (g/dl). After 18 days, a significant improvement was noted in all the clinical features, blood investigations, Chest X ray of the patient and no any unwanted effects were noted during the study period. The case was managed without encountering any adverse effects, following the treatment regimen for Shotha. Keywords: Diabetic Microalbuminuria, Hypoalbuminemia, Kaphaja Shotha

Unveiling the Anti-Cholera and Active Diabetic Renoprotective Compounds of Maqian Essential Oil: A Computational and Molecular Dynamics Study.

Cholera is an exceptionally aggressive infectious disease characterized by the potential to induce acute, copious, watery diarrhea of considerable severity and renal inflammation. Diabetic nephropathy is a serious complication of diabetes mellitus that can lead to kidney failure through inflammation; thus, anti-inflammatory agents are promising therapies for diabetic nephropathy. Previous studies have shown that the essential oil of Zanthoxylum myriacanthum var. pubescens Huang, Maqian essential oil (MQEO), exhibits potent antibacterial, anti-inflammatory, and renoprotective activities in diabetic mice and has emerged as a potential therapeutic drug for the treatment of diabetic nephropathy complications. Therefore, the present study was carried out to screen the potential inhibition of cholera toxin and the diabetic renoprotective activity of MQEO through computational approaches. Twelve chemical constituents derived from MQEO were docked with cholera toxin and the target proteins involved in diabetic nephropathy, namely, TXNIP, Nrf2, and DPP IV, and, subsequently, the predictions of molecular dynamic simulations, the drug-likeness properties, and the ADMET properties were performed. α-terpineol showed high binding affinities toward the cholera toxin protein. For TXNIP, among all the chemical constituents, α-phellandrene and p-cymene showed strong binding affinities with the TXNIP protein and displayed relatively stable flexibility at the hinge regions of the protein, favorable physicochemical properties in the absence of hepatotoxicity, and low cytotoxicity. For Nrf2, α-terpineol exhibited the highest binding affinity and formed a very stable complex with Nrf2, which displayed high pharmacokinetic properties. All compounds had low free-binding energies when docked with the DPP IV protein, which suggests potent biological activity. In conclusion, based on a computational approach, our findings reveal that MQEO constituents have inhibitory activity against cholera toxin and are promising therapeutic agents for suppressing diabetic inflammation and for the treatment of diabetic nephropathy complications.

Nanomedicines for the management of diabetic nephropathy: present progress and prospects.

Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and progress of DN depend heavily on early detection and effective treatment. DN is a major contributor to end-stage renal disease, and a complete cure is yet to be achieved with currently available options. Though some therapeutic molecules have exhibited promise in treating DN complications, their poor solubility profile, low bioavailability, poor permeation, high therapeutic dose and associated toxicity, and low patient compliance apprehend their clinical usefulness. Recent research has indicated nano-systems as potential theranostic platforms displaying futuristic promise in the diagnosis and treatment of DN. Early and accurate diagnosis, site-specific delivery and retention by virtue of ligand conjugation, and improved pharmacokinetic profile are amongst the major advantages of nano-platforms, defining their superiority. Thus, the emergence of nanoparticles has offered fresh approaches to the possible diagnostic and therapeutic strategies regarding DN. The present review corroborates an updated overview of different types of nanocarriers regarding potential approaches for the diagnosis and therapy of DN.

Nanocarriers and Diabetes: New Vistas and the Way Ahead.

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.

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.

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy

ABSTRACT Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Comparations Of Glycated Albumin Among Type 2 Diabetes Mellitus Patient With Normoalbuminuria, Microalbuminuria And Macroalbuminuria

Diabetic nephropathy is the most often complication of diabetes mellitus (DM). Complications of diabetic nephropathy can occur through several pathways, one of which is the formation of Advanced Glycation End Products (AGEs) through the formation of Glycated Albumin (GA). Glycated albumin (GA) is a medium-term glycemic control (2-3 weeks), shorter duration than HbA1c (2-3 months). The aim of this study was to compare the levels of GA in T2DM patients with normoalbuminuria, microalbuminuria, and macroalbuminuria. This is a cross-sectional study with subjects were 105 outpatients who had been diagnosed with T2DM by clinicians at Hasan Sadikin Hospital’s Endocrinology Clinic. We examined urinary albumin per Creatinine (u-ACR) and blood GA Increased GA level was found in 75.24% subjects. Kruskal Wallis test in GA serum levels of patients with T2DM normoalbuminuria group, microalbuminuria and macroalbuminuria revealed statistically significant (p &lt;0.001), with median and range of GA in normoalbuminuria 15,9% (12,1-21,89)%; microalbuminuria 20,9% (12,9-47,2)%; dan macroalbuminuria 23,1% (13,6-46,1)%. Statistical analysis showed that the GA serum level was significantly different between T2DM patients with normoalbuminuria and macroalbuminuria, but not between those with microalbuminuria and macroalbuminuria (p=0.001 and p=0.137, respectively). The result showed that the extensive kidney damage at the subject, the higher result of Glycated Albumin level in serum.

STUDY OF MICROALBUMINURIAAND ALBUMIN - CREATININE RATIO IN TYPE 2 DIABETES MELLITUS AND THEIR CORRELATION WITH GFR AND OTHER BIOCHEMICAL PARAMETERS

Diabetes mellitus (DM) is one of the primary risk factors for developing renal impairment globally. The development of microalbuminuria has been considered to be one of the rst clinical signs of a classic course of diabetic nephropathy, which leads to macroalbuminuria and then to progressive loss of glomerular ltration rate (GFR) and eventually end-stage renal disease. Both type 1 and type 2 DM may lead to chronic complication of diabetic nephropathy (DN). The development of microalbuminuria has been considered to be one of the rst clinical signs of a classic course of diabetic nephropathy, which leads to macroalbuminuria and then to progressive loss of glomerular ltration rate (GFR) and eventually end-stage renal disease. Persistent macroalbuminuria predicts loss of kidney function and, more importantly, interventions that reduce macroalbuminuria also slow the loss of glomerular ltration rate. this prospective observational study was designed in an attempt to evaluate the relationship between microalbuminuria, albumin-creatinine ratio with other biochemical parameters in type 2 DM and to examine whether this relation differs from that of non-diabet

Naringin prevents diabetic nephropathy in rats through blockage of oxidative stress and attenuation of the mitochondrial dysfunction.

We have studied the effects of naringin (NAR), a flavonoid from citric fruits, on morphology, ultrastructure and function of the kidney in streptozotocin (STZ)-induced diabetic rats. Two groups of animals were used: (1) control rats and (2) STZ rats (60mg STZ/kg b.w.). At 3 days after induction, one group of STZ-treated rats received 40mg NAR/kg b.w. daily. NAR blocked completely alterations in the biochemical renal markers in STZ rats except the increase in serum urea that was partially avoided by the flavonoid. NAR ameliorated the kidney morphological lesions from STZ rats. STZ treatment induced round and smaller mitochondria, which was avoided by NAR. Citrate synthase, isocitrate and malate dehydrogenases, enzyme activities of the Krebs cycle, were decreased in STZ rats. NAR abolished this decrease in the latter proteins. NAR also prevented a decrease in the ATP synthase activity of the mitochondria from renal cortex by about 49% in STZ rats, returning the enzyme activity to control values. The nephroprotection caused by NAR is mediated through counteraction of oxidative stress in mitochondria of proximal tubules. NAR might be a therapeutic strategy to reduce the complication of diabetic nephropathy in type 1 diabetic patients.

STUDY OF DOSAGE ADJUSTMENT OF ORAL ANTIDIABETIC DRUG IN TYPE II DIABETES MELLITUS PATIENTS WITH DISORDERS KIDNEY FUNCTION AT DR. SOEKARDJO TASIKMALAYA HOSPITAL

Diabetic nephropathy is one of the complications in DM that can end up becoming DM kidney failure. Nephropathy complications, if not handled properly, will lead to terminal chronic kidney disease. One of the factors that trigger complications of diabetic nephropathy in DM patients is the long-term use of oral anti-diabetic drugs. Therefore, proper dosage adjustment of these antidiabetic drugs, which are excreted through the kidneys, is required. The purpose of this study was to determine whether the dose received by type II DM patients with impaired renal function in the hospital was appropriate or not. This research will be carried out quantitatively and retrospectively by collecting patient medical record data at the hospital, and then the data obtained will be analyzed descriptively by calculating the creatinine clearance using the Cockcroft &amp; Gault formula and comparing it with the literature dose based on the value of creatinine clearance. The sampling technique used was purposive sampling using the inclusion and exclusion criteria determined by the researcher. The inclusion criteria are data on type II diabetes mellitus patients with impaired kidney function at dr. Soekardjo Tasikmalaya Hospital in October–December 2020 who were treated with oral anti-diabetic drugs. The exclusion criteria were type II DM patients with impaired renal function who were treated with insulin, type I DM patients, and type II DM patients with impaired renal function who were treated with oral antidiabetic with incomplete laboratory data. Based on research that has been conducted on 35 samples, as many as 25 people, or 71.43 percent of patients, received therapeutic doses that were not in accordance with their kidney conditions. Meanwhile, 10 people, or 28,57% of patients, received a therapeutic dose according to their kidney condition.

Assesment of serum taurine level as a potential biomarker for early diagnosis of diabetic nephropathy

Objective: Measuring of serum taurine as an early marker to detect and prevent complications of Diabetic nephropathy. Method: Ninty diabetic patients (male and female) were chosen from Ahmed Maher hospital after their approval, eighty patients classified into four groups (diabetic control group, early stage group, before dialysis group, after dialysis group) according to its Complete clinical examination, investigation and biochemical analysis, twenty diabetic controlled patients not suffered from kidney impairment considered as diabetic control group. ten frank healthy non diabetic persons enrolled as volunteers. Complete clinical examination, investigation and biochemical analysis (liver and kidney functions, lipid profile), add to measuring Blood sugar, HbA1c, and the recent biomarker taurine, was measured for all patient and volunteers. Results: The data showed non-significant change in lipid profile, creatinine in urine, and serum Albumine in all patients regarding to control group (P&gt;0.05). that Liver function in all groups demonstrated non significance between groups,but values recorded significant changes in all groups of patients related to frank control group (p&lt;0.05). Kidney function (urea – creatinine) values recorded very highly significant changes in all groups of patients related to frank control group (p&lt;0.00), except controlled diabetic group and Early stage of diabetic nephropathy. also, there is a highly significant changes in blood glucose and HbA1c (P&gt;0.001). On the other hand, the data showed extremely significant decrease in serum taurine in all diabetic patients according to the severity of diabetic nephropathy compared to that recorded in healthy control (P&lt;0.000). Conclusion: Serum taurine is reduced in diabetic patients with advanced conditions of diabetic nephropathy. Taurine Level is considered as an early marker (prognostic) to detect and prevent the diabetic nephropathy complications.

Blood glucose management in type 1 diabetes

Journal of Kidney CareVol. 7, No. 6 Keeping up with Kidney CareBlood glucose management in type 1 diabetesPeter EllisPeter EllisEmail: E-mail Address: [email protected]Health and Social Care Consultant, Writer and EducatorSearch for more papers by this authorPeter EllisPublished Online:22 Nov 2022https://doi.org/10.12968/jokc.2022.7.6.310AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Arnqvist HJ, Westerlund MC, Fredrikson M, Ludvigsson J, Nordwall M. Impact of HbA1c followed 32 years from diagnosis of type 1 diabetes on development of severe retinopathy and nephropathy: the VISS study. Diabetes Care. 2022 (online ahead of print). https://doi.org/10.2337/dc22-0239 Google ScholarKidney Disease: Improving Global Outcomes Diabetes Working Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney International. 2020; 98(4):S1–S115. https://doi.org/10.1016/j.kint.2020.06.019 Google ScholarLim AKH. Diabetic nephropathy—complications and treatment. Int J Nephrol Renovasc Dis. 2014; 7:361–381. https://doi.org/10.2147/IJNRD.S40172. Google ScholarNational Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. 2015. www.nice.org.uk/guidance/ng17/chapter/Recommendations#blood-glucose-management (accessed 13 October 2022) Google Scholar FiguresReferencesRelatedDetails 2 November 2022Volume 7Issue 6ISSN (print): 2397-9534ISSN (online): 2397-9542 Metrics History Published online 22 November 2022 Published in print 2 November 2022 Information© MA Healthcare LimitedKeywordsdiabeteschronic kidney diseaseblood glucose levelsPDF download

Concordance of Proteinuria Examination Results using Dipstick Urine, Albumin-Creatinine Ratio, and Immunoassay in Diabetes Mellitus Type-2

Periodic examination of proteinuria for DM patients is important for the prevention of diabetic nephropathy complications. The most commonly used methods for checking proteinuria today are urine dipstick, albumin-creatinine ratio, and immunoassays. To analyze the suitability of proteinuria examination using a urine Dipstick, Albumin-Creatinine Ratio, and immunoassay. An observational analytic study, cross sectional, conducted in July 2020 - October 2020 at the Dr. Soetomo Surabaya, using urine samples (n = 57) that met the inclusion and exclusion criterias. The suitability test was carried out between the AIM urine dipstick, urine sysmex dipstick, AIM immunoassay and the Sysmex UC 3500 AC Ratio which were analyzed by the Cohen's kappa test. Immunoassay detected the highest proteinuria in 85.96% of type 2 DM patients, followed by AC Ratio (68.42%), AIM Dipstick (52.6%), and Sysmex Dipstick (49.12%). There was a very strong agreement between the AIM Dipstick and the Sysmex Dipstick, κ = 0.86 (p&lt;0.05), a weak agreement between AIM immunoassay examination and Sysmex AC ratio, κ = 0.37 (p&lt;0.05). There is no agreement between the Sysmex urine disptick and AIM immunoassay. There is a low agreement between the AIM Dipstick and the Sysmex AC Ratio. The AIM immunoassay detected microalbuminuria in 10(55.6%) of 18 subjects with negative results on Sysmex. Most immunoassay examinations detect proteinuria in type 2 DM patients. It is advisable to screen proteinuria using an immunoassay examination in type 2 DM patients1. Immunoassay examination can be relied on in screening proteinuria in DM patients. The results showed a very strong agreement using the AIM and the Sysmex dipstick examination. However, there was a weak agreement between the immunoassay examination and the AC ratio.

Relationship Between Sporadic Renal Cysts and Renal Function Detected by Isotope Renography in Type 2 Diabetes.

PurposeThis study aimed to reveal the relationship between the volume of sporadic renal cysts and renal function in patients with type 2 diabetes (T2D).Materials and MethodsOne hundred and seventy-one patients that underwent renal imaging and other routine examinations at the Shanghai Pudong Hospital were included in this study. The Gates’ method of glomerular filtration rate (GFR) was measured by 99mTc-DTPA renal dynamic imaging in addition to the eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI).ResultsOur results showed that BMI, total iGFR, and eGFR showed significant differences between patients with T2D with or without SRC (p < 0.05). Spearman correlation analysis showed that cyst volume was positively correlated with Scr and gender but not iGFR (p > 0.05). The total iGFR positively correlated with eGFR (r = 0.83, p < 0.0001) and negatively with Scr (r = −0.78, p < 0.0001), age (r = −0.43, p < 0.0001), duration of T2D (r = −0.25, p = 0.001), and BMI (r = −0.21, p = 0.006) but not gender (r = −0.03, p = 0.668). The multilinear regression model revealed that gender (β = 0.346, p < 0.001), iGFR (β = −0.705, p < 0.001), and serum uric acid (β = 0.195, p = 0.032) were independent predictors of Scr. Moreover, we observed a significant increase in Scr in males (p < 0.05). Finally, we found that the split kidney function reflected by iGFR and related parameters such as time to peak (PTT) and half time of excretion (excrete t1/2) did not mutually distinguish from each other significantly whether they are measured in patients with renal cysts or in those without renal cysts (p > 0.05).ConclusionOur preliminary results suggest that in T2D, SRCs may be a renal complication of diabetic nephropathy. Although we found that the patients with renal cysts may display reduced iGFR, the volume of simple cysts seems not to exacerbate renal insufficiency. Isotope renography is a useful tool to evaluate the split kidney functions in diabetic patients who acquire single-side cysts.

Antioxidative Stress and Anti-Inflammatory Activity of Fucoidan Nanoparticles against Nephropathy of Streptozotocin-Induced Diabetes in Rats.

Oxidative stress and inflammation have been shown to interact and have the role of importance in causing diabetic nephropathy complications. Fucoidan has a strong antioxidant and anti-inflammation effect, so the aim of this research was to evaluate the antioxidative stress and anti-inflammatory effect of fucoidan nanoparticles against nephropathy of streptozotocin-induced diabetes in rats. Fucoidan nanoparticles are characterized using dynamic light scattering (DLS) and scanning electron microscope (SEM). The rats were randomized into the control group (were given with aquadest), streptozotocin group (were injected with streptozotocin at a dose of 55 mg/kg BW i.p.), and fucoidan nanoparticle group (were given orally with fucoidan at doses 75, 150, and 300 mg/kg BW and then injected streptozotocin at a dose of 55 mg/kg BW i.p.). The blood was taken to evaluate the level of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to measure malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) by ELISA; superoxide dismutase (SOD), and glutathione peroxidase (GPx) by immunohistochemical staining and histological observation by Hematoxylin & Eosin (H&E) staining. The DLS demonstrated that the fucoidan nanoparticle size was 330.6 ± 58.8 nm, and the SEM showed an irregular shape with a rough surface image. The administration of streptozotocin significantly increased BUN, creatinine, MDA, IL-6, and TNF-α levels, whereas expression of SOD and GPx decreased as compared with the control group (p < 0.05). The administration of fucoidan nanoparticles only at a dose of 300 mg/kg BW significantly decreases BUN, creatinine, MDA, IL-6, and TNF-α levels. However, fucoidan nanoparticles at a dose of 300 mg/kg BW significantly increase SOD and GPx expression as compared with the streptozotocin group (p < 0.05). The administration of streptozotocin caused the loss of normal kidney cell structure and necrosis, while treatment with fucoidan nanoparticles improved renal cell necrosis. It can be concluded that fucoidan nanoparticles are promising agents in terms of the protection afforded against streptozotocin-induced nephropathy through antioxidative stress by decreasing MDA and increasing SOD and GPx and through anti-inflammatory effect by decreasing levels of IL-6 and TNF-α.

A Novel Study of Protein Kinase C Beta Gene Polymorphism (rs3760106) and Protein Kinase C Activity Levels as a Predictor of Nephropathy Complications in Iraqi Diabetic Patients

Objective: This study aimed to investigate the relation between the risk of (PRKCB-1504 C/T) gene polymorphisms and diabetic nephropathy pathogenesis and its association with its levels and some other biomarkers in serum of Iraqi diabetic nephropathy patients.&#x0D; Methods: A cross-sectional study was performed on 130 samples obtained from Al-Hussein Teaching Hospital / Kerbala – Iraq during Feb., 2020 to March. 2021. Seventy three patients of them with type 2 diabetes mellitus (T2D) and the remaining patients with type 2 diabetes mellitus with nephropathy complications (DN). Phenotypic analysis included determination of protein kinase C (PKC) activity levels, HbA1c%, serum insulin levels and renal function tests. Five ml of whole blood was obtained from each patients, 4.0 ml was centrifuged for serum separation used for biomarkers determinations and the remaining 1.0 ml was used for genomic DNA extraction for molecular analysis and polymorphism of PRKCB (rs3760106) by allele specific-amplification refractory mutational system-polymerase chain reaction (allele specific ARMS-PCR), followed by electrophoresis on 1% agarose gel. Various statistical analyses were applied to analyze the obtained data.&#x0D; Results: The amplification of the PRKCB gene gives one genotypes as indicated by (200 bp) bands for those with homozygous wild type (CC), homozygous mutant (TT) genotypes and two genotypes bands (200 bp) for those with heterozygous (CT). Genotype frequencies of rs3760106 polymorphism were found to be consistent with Hardy–Weinberg equilibrium. Allele frequencies (23.3 %, 26.7 %, 50 %) of CC, CT, TT in cases of DN group. While the frequencies in the non-DN group were (30 %, 45%, 25%) and for healthy control group were (50%, 33.4%, 16.6%) for wild, heterozygous, and homozygous in an order. In healthy control group, the risk of diabetic nephropathy was significantly higher among carriers of T allele under codominant TT (OR=6.42, 95%CI=(1.66-24.85), P=0.007), dominant CT+TT (OR=3.2, 95%CI = (1.08-9.95),P=0.03) and recessive model (OR=5, 95%CI = (1.51-16.56), P=0.008) while in T2DM without nephropathy the risk of diabetic nephropathy was significantly higher among carrier of T allele under recessive model (0R=3, 95%CI = (1.09-28.25), P= 0.003). Serum level of PKC-B1 activity was significantly higher among DN group than T2DM and control groups (43.35 ± 18.69, 30.35 ± 11.96, 27.42 ± 10.31, P=0.001), also PKC-B1 activity in DN group was significantly correlated with fasting blood glucose, HOMA-IR and renal function tests such as GFR, urea and creatinine.&#x0D; Conclusion: This study indicates that the PRKCB (C/T-1504) rs3760106 single nucleotide polymorphism was significantly associated with increased diabetic nephropathy susceptibility of Iraqi patients with T2DM and serum level of PKCB activity was associated with increase the risk of diabetic nephropathy complications.

Assessment of risk factors associated with diabetes

Objective: Purpose of the study was to assess to risk factors of diabetes type II and complications in diabetic patient of tertiary care hospital. Methods/Design: Cross sectional study conducted to evaluate the risk factors associated with diabetes Mellitus. Setting: Tertiary hospitals of Islamabad and Azad Kashmir was selected for the current study. Participants: 50 patients assessed without any gender discrimination age between 35 to 85 years for risk factors and complications. Intervention: Data was collected from patients that were bed ridden admitted in hospitals. A total of 50 patients were included in this study with age limit more than 35 years and without any discrimination of gender. Primary Outcome Measures: In tertiary care hospitalized patient’s obesity, inactivity and family history were the major risk factor for diabetes mellitus type 2 and we calculated the obesity, inactivity and family history percentage in diabetic patients 63%, 49% and 67% respectively. Results: Percentage of risk factors calculated the obesity, inactivity and family history in diabetic patients 63%, 49% and 67% respectively. Macro vascular complications in patients with diabetes mellitus type 2 were stroke 3%, angina 8%, hypertension and cognitive impairment have highest percentages i.e., 78%. 46% patients were suffering from ulceration; gangrene and amputation have percentages 19% and 3% respectively. Patients with microvascular complications of diabetic nephropathy were assessed for their albuminuria 25%, edema 32% and incontinence 28%. Conclusion: These complications can be avoided if patients of DM type 2 adopt a healthy lifestyle, do exercise and monitor their blood glucose levels regularly. Patients should also control their blood pressure to avoid damage to their microvasculature.

Investigation of angiotensin-1 converting enzyme 2 gene (G8790A) polymorphism in patients of type 2 diabetes mellitus with diabetic nephropathy in Pakistani population.

BackgroundType 2 diabetes mellitus is a multifactorial disease that escalates the risk of other associated complications such as diabetic neuropathy, retinopathy, and nephropathy. Diabetic nephropathy is a microvascular condition that leads to end-stage renal disease (ESRD). There are several genes involved in disease development and it is a challenging task to investigate all of these. Nonetheless, identifying individual gene roles can assist in evaluating the combinatorial effects with other genes. Angiotensin-1 converting enzyme 2 (ACE2), is the key regulator of blood pressure in the Renin-Angiotensin-Aldosterone System that hydrolyzes angiotensin II (vasoconstrictor) into angiotensin 1–7 (vasodilator). The association of different variants of the ACE2 with the risk of type 2 diabetes mellitus has been determined in various populations with susceptibility to other complications. This study was aimed to investigate the association of Angiotensin-1 converting enzyme 2 polymorphism, G8790A, with the increased risk of type 2 diabetes mellitus (T2DM) development with the complication of diabetic nephropathy (DN) in the Pakistani population.MethodsIn this case-control study, a total of 100 healthy controls and 100 patients of type 2 diabetes mellitus aged > 40 years, having disease duration ≥ 10 years were compared. The G8790A polymorphism in ACE2 was analyzed by allele-specific polymerase chain reaction (AS-PCR). The urinary albumin excretion (UAE), urinary creatinine, and albumin to creatinine ratios (ACR) were determined to assess renal function status. Pearson bivariate correlation coefficients were calculated to investigate the relationship among all the parameters. Crude and adjusted odds ratios were found to determine any risk association between ACE2 G8790A polymorphisms and disease development. The p-values < 0.05 were considered significant.ResultsA homogeneity was obtained regarding the distribution of data by sex, BMI, diastolic blood pressure, pulse rate and urinary creatinine levels between case and control groups. The ACR showed a significant correlation with UAE (r = 0.524, p = 0.001), urinary creatinine (r = -0.375, p = 0.001) and random blood sugar levels (r = 0.323, p = 0.005) with the complication of diabetic nephropathy in T2DM patient. Females with the AA genotype had a 10-fold increased risk for the development of type 2 Diabetes (OR = 9.5 [95% CI = 2.00–21.63] p<0.002). Males having A allele showed a significant association for susceptibility of type 2 Diabetes (OR = 3.807 [95% CI = 1.657–8.747] p<0.002). However, none of the genotypes or alleles revealed an association for diabetic nephropathy in male and female patients. Urinary ACR was also found to be positively correlated with UAE (r = 0.642 p = 0.001 & 0.524, p = 0.001) and random blood sugar levels (r = 0.302, p = 0.002 & r = 0.323, p = 0.005) in T2DM and T2DM+DN groups, respectively.ConclusionThe study finding indicated that female AG/AA genotype and male A genotype of G8790A polymorphism in the ACE2 gene were associated with type 2 diabetes mellitus as a genetic risk factor but are not associated with diabetic nephropathy in the Pakistani population.

Association of C-Reactive Protein with Risk of Complications of diabetic nephropathy

Association of C-Reactive Protein with Risk of Complications of diabetic nephropathy