• Title/Summary/Keyword: diabetic nephropathy.

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The Amputation Rate and Associated Risk Factors within 1 Year after the Diagnosis of Diabetic Foot Ulcer (당뇨병성 족부 궤양 환자의 진단 1년 내의 절단율 및 위험 인자의 분석)

  • Chun, Dong-Il;Jeon, Min Chul;Choi, Sung-Woo;Kim, Yong-Beom;Nho, Jae-Hwi;Won, Sung Hun
    • Journal of Korean Foot and Ankle Society
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    • v.20 no.3
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    • pp.121-125
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    • 2016
  • Purpose: This study investigates the amputation rate within 1 year after the diagnosis of diabetic foot ulcer and its associated risk factors. Materials and Methods: This study enrolled 60 patients with diabetic foot ulcer. The mean and standard deviation age was $64.4{\pm}12.8years$ (range, 32~89 years); the mean and standard deviation prevalence period for diabetes mellitus was $21.0{\pm}7.5years$ (range, 0.5~36 years). The amputation rate was evaluated by dividing the subjects into two groups - the major and minor amputation groups - within 1 year following the initial diagnosis of diabetic foot ulcer. Multivariate Cox proportional hazards regression analysis was used to identify the risk factors for amputation. Results: The total amputation rate of 38.3% (n=23) was comprised of the amputation rate for the major amputation group (10.0%) and rate for the minor amputation group (23.8%). There was a high correlation between peripheral artery disease (toe brachial pressure index <0.7) and amputation (hazard ratio [HR] 5.81, confidence interval [CI] 2.09~16.1, p<0.01). Nephropathy was significantly correlated with the amputation rate (HR 3.53, CI 1.29~9.64, p=0.01). Conclusion: Clinicians who treat patients with diabetic foot complications must understand the fact that the amputation rate within 1 year is significant, and that the amputation rate of patients with peripheral artery disease or nephropathy is especially high.

Specific Alternation of Gut Microbiota and the Role of Ruminococcus gnavus in the Development of Diabetic Nephropathy

  • Jinni Hong;Tingting Fu;Weizhen Liu;Yu Du;Junmin Bu;Guojian Wei;Miao Yu;Yanshan Lin;Cunyun Min;Datao Lin
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.547-561
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    • 2024
  • In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact of Ruminococcus gnavus (R. gnavus) on DN. Eight-week-old male KK-Ay mice were administered antibiotic cocktails for a duration of two weeks, followed by oral administration of R. gnavus for an additional eight weeks. Our study revealed significant changes in the gut microbiota during both the initiation and progression of DN. Specifically, we observed a notable increase in the abundance of Clostridia at the class level, higher levels of Lachnospirales and Oscillospirales at the order level, and a marked decrease in Clostridia_UCG-014 in DN group. Additionally, there was a significant increase in the abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Moreover, oral administration of R. gnavus effectively aggravated kidney pathology in DN mice, accompanied by elevated levels of urea nitrogen (UN), creatinine (Cr), and urine protein. Furthermore, R. gnavus administration resulted in down-regulation of tight junction proteins such as Claudin-1, Occludin, and ZO-1, as well as increased levels of uremic toxins in urine and serum samples. Additionally, our study demonstrated that orally administered R. gnavus up-regulated the expression of inflammatory factors, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) and Interleukin (IL)-6. These changes indicated the involvement of the gut-kidney axis in DN, and R. gnavus may worsen diabetic nephropathy by affecting uremic toxin levels and promoting inflammation in DN.

Screening of Korean Herbal Medicines with Inhibitory Effect on Aldose Reductase (IX) (한국 약용식물 추출물의 알도즈 환원 효소 억제 효능 검색(IX))

  • Choi, So-Jin;Kim, Young Sook;Kim, Joo Hwan;Kim, Jin Sook
    • Korean Journal of Pharmacognosy
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    • v.45 no.4
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    • pp.354-358
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    • 2014
  • Aldose reductase (AR) has been demonstrated to play important role in the development of the diabetic complications such as diabetic retinopathy, diabetic neuropathy and diabetic nephropathy. To discover novel treatments for diabetic complications from natural sources, 69 Korean herbal medicines have been investigated for inhibitory activities on AR. Among them, 7 herbal medicines, Eleutherococcus sessiliflorus (stems), Artemisia japonica (whole plants), Wisteria floribunda (leaves), Eurya japonica (stems, twigs and leaves, leaves), Ampelopsis brevipedunculata (stems) exhibited a significant inhibitory activity compared with 3,3-tetramethyleneglutaric acid as positive control.

Regulator of Calcineurin 1 Isoform 4 (RCAN1.4) Is Overexpressed in the Glomeruli of Diabetic Mice

  • Jang, Cho-Rong;Lim, Ji-Hee;Park, Cheol-Whee;Cho, Young-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.5
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    • pp.299-305
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    • 2011
  • Calcineurin (CaN) is activated in diabetes and plays a role in glomerular hypertrophy and extracellular matrix (ECM) accumulation. Here, kidneys from diabetic model mice were investigated for the expression of the regulator of CaN 1 (RCAN1) isoform 4 (RCAN1.4) which had been shown to be transcriptionally upregulated by CaN activation. We found the increased immunoreactivity for RCAN1 in the glomerular cells of db/db mice and streptozotocin-induced diabetic mice. In concordance, the expression of RCAN1 protein and RCAN1.4 mRNA were elevated in the whole kidney sample from db/db mice. Interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$, and glycated albumin (AGE-BSA) were identified as inducers of RCAN1.4 in mesangial cells. Pretreatment of cyclosporine A blocked the increases of RCAN1.4 stimulated by IL-$1{\beta}$ or AGE-BSA, suggesting that activation of CaN is required for the RCAN1.4 induction. Stable transfection of RCAN1.4 in Mes-13 mesangial cells upregulated several factors relevant to ECM production and degradation. These results suggested that RCAN1.4 might act as a link between CaN activation and ECM turnover in diabetic nephropathy.

Review on the association between glucose control and mortaliy in diabetic patients (당뇨병에서 혈당조절과 사망률의 연구에 관한 소고)

  • Kahng, Hyun-Un
    • The Journal of the Korean life insurance medical association
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    • v.30 no.2
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    • pp.16-19
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    • 2011
  • In patents with diabetes, the higher the serum glucose level was, the more cardiovascular events and death were observed. But with a certain kind of group, to control glucose level tightly does not decrease the incidence of these events. Several studies show that intensive glucose control does not gain benefit in patient with long standing, uncontrolled diabetes, especially having previous cardiovascular events, while definitely preventing progression of newly onset of diabetic nephropathy. Whether intensive glucose control increases mortality in high risk group is obscure and needs more studies with longer observation time.

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Effect of atorvastatin on dendritic cells of tubulointerstitium in diabetic rats

  • Tu, Yafang;Jia, Ruhan;Ding, Guohua;Chen, Ling
    • BMB Reports
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    • v.43 no.3
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    • pp.188-192
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    • 2010
  • Inflammatory reactology has become increasingly important in diabetic kidney disease. In this study, we estabilished STZ-induced diabetic rat model to investigate whether dendritic cells (DCs) mediated tubulointerstitial damages, and whether the effects by DCs were mediated by P-selectin expression and can be inhibited by atorvastatin. The study demonstrated that there was an accumulation of DCs in diabetic rats mediated by P-selectin. It also showed the accumulation of DCs and expression of P-selectin was closely correlated with the degree of renal tubulointerstitial injury. These effects were markedly attenuated by atorvastatin. Thus, DCs play a role in tubulointerstitial damages, atorvasttin can prevent renal tubulointerstitium from damage by inhibiting the P-selectin expression and DCs migration.

Effect of Supplementation of Dietary Sea Tangle on the Renal Oxidative Stress in Diabetic Rats (식이 다시마의 섭취가 당뇨 쥐 신장의 산화적 스트레스 및 당뇨성 병변에 미치는 영향)

  • Park, Min-Young;Kim, Kyung-Hee;Jeong, Kyu-Shik;Kim, Hyeon-A
    • Journal of the Korean Society of Food Culture
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    • v.22 no.1
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    • pp.140-148
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    • 2007
  • Diabetic nephropathy has been increasing, although blood glucose and blood pressure can be controlled by angiotensin converting enzyme(ACE) or advanced glycosylation end products(AGE) inhibitors in the diabetic patients. We investigated the effect of dietary supplementation of sea tangle on the blood glucose, and pathological scoring of diabetic kidneys in the streptozotocin(STZ) induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet and diabetic rats fed control diet or control diet supplemented with powder or oater extract of sea tangle. Diabetes was induced by a single injection of STZ(60mg/kg, ip) in citrate buffer. The animals were fed the experimental diet and water for 13 weeks. Dietary supplementation of sea tangle decreased blood glucose in the diabetic rats. However, dietary supplementation of sea tangle did not affect the antioxidant enzyme activities, MDA content and pathology of diabetic kidneys. These results indicate that decreased blood glucose by sea tangle could not delay the progression of diabetic kidney disease.

Plasminogen Activator Inhibitor-1 Antisense Oligodeoxynucleotides Abrogate Mesangial Fibronectin Accumulation

  • Park, Je-Hyun;Seo, Ji-Yeon;Ha, Hun-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.6
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    • pp.385-390
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    • 2010
  • Excessive extracellular matrix (ECM) accumulation is the main feature of chronic renal disease including diabetic nephropathy. Plasminogen activator inhibitor (PAI)-1 is known to play an important role in renal ECM accumulation in part through suppression of plasmin generation and matrix metalloproteinase (MMP) activation. The present study examined the effect of PAI-1 antisense oligodeoxynucleotide (ODN) on fibronectin upregulation and plasmin/MMP suppression in primary mesangial cells cultured under high glucose (HG) or transforming growth factor (TGF)-${\beta}1$, major mediators of diabetic renal ECM accumulation. Growth arrested and synchronized rat primary mesangial cells were transfected with $1\;{\mu}M$ phosphorothioate-modified antisense or control mis-match ODN for 24 hours with cationic liposome and then stimulated with 30 mM D-glucose or 2 ng/ml TGF-${\beta}1$. PAl-1 or fibronectin protein was measured by Western blot analysis. Plasmin activity was determined using a synthetic fluorometric plasmin substrate and MMP-2 activity analyzed using zymography. HG and TGF-${\beta}1$ significantly increased PAI-1 and fibronectin protein expression as well as decreased plasmin and MMP-2 activity. Transient transfection of mesangial cells with PAI-1 antisense ODN, but not mis-match ODN, effectively reversed basal as well as HG- and TGF-${\beta}1$-induced suppression of plasmin and MMP-2 activity. Both basal and upregulated fibronectin secretion were also inhibited by PAI-1 antisense ODN. These data confirm that PAI-1 plays an important role in ECM accumulation in diabetic mesangium through suppression of protease activity and suggest that PAI-1 antisense ODN would be an effective therapeutic strategy for prevention of renal fibrosis including diabetic nephropathy.

Comparative co-expression analysis of RNA-Seq transcriptome revealing key genes, miRNA and transcription factor in distinct metabolic pathways in diabetic nerve, eye, and kidney disease

  • Asmy, Veerankutty Subaida Shafna;Natarajan, Jeyakumar
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.26.1-26.19
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    • 2022
  • Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.