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1.
N Z Med J ; 133(1510): 35-44, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32078599

RESUMO

AIMS: To determine whether glycaemic control and the prevalence of microvascular complications in Waikato children/youth with type 1 diabetes (T1D) has changed since 2003. METHODS: A retrospective review was performed of clinical records of children and youth with T1D who were under the care of the Waikato Paediatric and Young Adult Diabetes Services between March 2016 and March 2017. Comparisons were made to published data from the same service in 2003. RESULTS: Despite a more than two-fold increase in insulin-pump therapy since 2003, glycaemic control was not significantly improved in either children or youth. However, since 2003 there has been a significant reduction in the prevalence of diabetic retinopathy (24.6% vs 6.0%; P=0.003) and nephropathy (6.0% vs 25.4%; P=0.002), while symptomatic diabetic neuropathy remains rare. This reduction occurred despite a significant increase in obesity and hypertension, and no significant difference in the rates of dyslipidaemia or smoking. CONCLUSIONS: There has been a marked reduction in microvascular complications in Waikato youth and young adults with type 1 diabetes, but the reasons for the reduction are not clear given there has been no significant improvements in glycaemic control.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/etnologia , Neuropatias Diabéticas/etnologia , Retinopatia Diabética/etnologia , Grupo com Ancestrais Oceânicos , Adolescente , Biomarcadores/sangue , Glicemia/metabolismo , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/etnologia , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Lactente , Recém-Nascido , Masculino , Nova Zelândia/epidemiologia , Prevalência , Estudos Retrospectivos
2.
Rev Assoc Med Bras (1992) ; 66Suppl 1(Suppl 1): s17-s24, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31939531

RESUMO

Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Nefropatias/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/farmacologia , Compostos Benzidrílicos/uso terapêutico , Canagliflozina/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/prevenção & controle , Taxa de Filtração Glomerular , Glucose/metabolismo , Glucosídeos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/etiologia , Nefropatias/metabolismo , Transportador 2 de Glucose-Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
3.
Am J Physiol Renal Physiol ; 318(2): F509-F517, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31904280

RESUMO

Endothelial dysfunction, characterized by reduced bioavailability of nitric oxide and increased oxidative stress, is a hallmark characteristic in diabetes and diabetic nephropathy (DN). High levels of asymmetric dimethylarginine (ADMA) are observed in several diseases including DN and are a strong prognostic marker for cardiovascular events in patients with diabetes and end-stage renal disease. ADMA, an endogenous endothelial nitric oxide synthase (NOS3) inhibitor, is selectively metabolized by dimethylarginine dimethylaminohydrolase (DDAH). Low DDAH levels have been associated with cardiac and renal dysfunction, but its effects on DN are unknown. We hypothesized that enhanced renal DDAH-1 expression would improve DN by reducing ADMA and restoring NOS3 levels. DBA/2J mice injected with multiple low doses of vehicle or streptozotocin were subsequently injected intrarenally with adenovirus expressing DDAH-1 (Ad-h-DDAH-1) or vector control [Ad-green fluorescent protein (GFP)], and mice were followed for 6 wk. Diabetes was associated with increased kidney ADMA and reduced kidney DDAH activity and DDAH-1 expression but had no effect on kidney DDAH-2 expression. Ad-GFP-treated diabetic mice showed significant increases in albuminuria, histological changes, glomerular macrophage recruitment, inflammatory cytokine and fibrotic markers, kidney ADMA levels, and urinary thiobarbituric acid reactive substances excretion as an indicator of oxidative stress, along with a significant reduction in kidney DDAH activity and kidney NOS3 mRNA compared with normal mice. In contrast, Ad-h-DDAH-1 treatment of diabetic mice reversed these effects. These data indicate, for the first time, that DDAH-1 mediates renal tissue protection in DN via the ADMA-NOS3-interaction. Enhanced renal DDAH-1 activity could be a novel therapeutic tool for treating patients with diabetes.


Assuntos
Adenoviridae/genética , Amidoidrolases/biossíntese , Arginina/análogos & derivados , Diabetes Mellitus Experimental/terapia , Nefropatias Diabéticas/prevenção & controle , Terapia Genética , Vetores Genéticos , Rim/enzimologia , Albuminúria/enzimologia , Albuminúria/genética , Albuminúria/prevenção & controle , Amidoidrolases/genética , Animais , Arginina/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/genética , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Fibrose , Mediadores da Inflamação/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos DBA , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Transdução de Sinais , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
4.
J Clin Nurs ; 29(5-6): 922-931, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31876037

RESUMO

AIM AND OBJECTIVES: To investigate factors related to self-management and predictors of self-management in older adult patients with type 2 diabetic nephropathy. BACKGROUND: Diabetic patients suffer many comorbidities during their lifetime, and the process of self-management is complex. Self-management and an integrated care experience are extremely important for older adults with diabetic nephropathy. DESIGN: A cross-sectional correlation design was adopted. METHODS: A total of 123 older patients were enrolled in the study from June 2016 to November 2017. Data collection involved a demographic questionnaire, the Patients' Experience of Integrated Care Questionnaire and the Partners in Health Scale to measure the integrated care experience and self-management. Data analysis included descriptive statistics, independent t tests, Pearson product-moment correlation and multiple linear regression. The methods are consistent with the STROBE criteria (Data S1). RESULTS: The results showed that the majority of the sample was female (56.9%). The average age was 77 years old. Stepwise regression analysis showed that re-admission during the past year (p < .001), physical function (p < .001) and integrated care experience (p < .001) are predictors of self-management in older adult patients with type 2 diabetic nephropathy and explained 42.8% of the variation in self-management behaviour. CONCLUSION: The results can be used to enhance the awareness of clinicians of the importance of an integrated care experience and self-management among older patients with type 2 diabetic nephropathy. Clinicians also should pay attention to physical function and the integrated care experience to promote self-management. RELEVANCE TO CLINICAL PRACTICE: Studies on the integrated care experience and self-management of diabetic neuropathy in older adults are limited in Taiwan. The results of this study provide valuable information to support the importance of integrated care among this specific population.


Assuntos
Nefropatias Diabéticas/terapia , Autogestão/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Taiwan
5.
Vasc Health Risk Manag ; 15: 503-508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802883

RESUMO

Purpose: The aim of this study is to prove that type 2 diabetes mellitus can induce increasing inflammation marker in renal and that the provision of darapladib as Lp-LA2 Inhibitor agents can inhibit inflammation that were measured from the expression of IL-1B and IL-6- type cytokine in renal. This study also discusses the correlation between IL-1B and IL-6- type cytokine expression in renal. Methods: Thirty Sprague-Dawley (SD) rats were divided into three main groups; those are negative control group (NC), Type 2 Diabetes Mellitus group (T2DM) given high fat diet (HFD) with streptozotocin intraperitoneal injection (35mg/kg BW) and diabetes mellitus + darapladib group (DM + DP). Each group was treated within two serial treatment time: 8 weeks and 16 weeks. Expressions of IL-1B and IL-6- type cytokine in renal were the markers that we measured by immunofluorosense method. Results: The administration of darapladib can significantly decrease the expression of IL-1B- type cytokine (p ANOVA = 0.029, p < 0.005) measured in rats' renal both at weeks 8 and 16 in the T2DM group. The Expression of IL-6- type cytokine also showed a significant difference after treated with darapladib both at weeks 8 and 16 in T2DM group with p-value of ANOVA = 0.033, p < 0.005. The Pearson correlation showed a strong correlation (linear regression value was r2 = 0.743). Conclusion: Our results show that atherosclerosis caused by inflammation in renal T2DM SD rats could be inhibited by the administration of darapladib.


Assuntos
Anti-Inflamatórios/farmacologia , Benzaldeídos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Oximas/farmacologia , Inibidores de Fosfolipase A2/farmacologia , Fosfolipases A2/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Regulação para Baixo , Rim/metabolismo , Ratos Sprague-Dawley
6.
Nat Commun ; 10(1): 4523, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586053

RESUMO

Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression.


Assuntos
Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Furanos/farmacologia , Lignanas/farmacologia , Podócitos/efeitos dos fármacos , Proteína Fosfatase 2/metabolismo , Animais , Arctium/química , Diabetes Mellitus Experimental/induzido quimicamente , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Furanos/uso terapêutico , Humanos , Lignanas/uso terapêutico , Masculino , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Óxido Nítrico Sintase Tipo III/genética , Podócitos/patologia , Podócitos/ultraestrutura , Proteína Fosfatase 2/genética , Estreptozocina/toxicidade , Resultado do Tratamento
7.
Life Sci ; 237: 116950, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605709

RESUMO

C-peptide is a small peptide connecting two chains of proinsulin molecule and is dissociated before the release of insulin. It is secreted in an equimolar amount to insulin from the pancreatic beta-cells into the circulation. Recent evidence demonstrates that it has other physiologic activities beyond its structural function. C-peptide modulates intracellular signaling pathways in various pathophysiologic states and, could potentially be a new therapeutic target for different disorders including diabetic complications. There is growing evidence that c-peptide has modulatory effects on the molecular mechanisms involved in the development of diabetic nephropathy. Although we have little direct evidence, pharmacological properties of c-peptide suggest that it can provide potent renoprotective effects especially, in a c-peptide deficient milieu as in type 1 diabetes mellitus. In this review, we describe possible molecular mechanisms by which c-peptide may improve renal efficiency in a diabetic milieu.


Assuntos
Peptídeo C/uso terapêutico , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/prevenção & controle , Animais , Complicações do Diabetes/etiologia , Nefropatias Diabéticas/etiologia , Humanos
8.
Diabetes Res Clin Pract ; 157: 107874, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593744

RESUMO

AIMS: To determine the predictability of diagnosing diabetic nephropathy (DN) versus non-diabetic renal disease (NDRD) from clinical and laboratory data in Chinese patients with type 2 diabetes mellitus (T2DM) manifesting heavy proteinuria. METHODS: We retrospectively analyzed the clinical and laboratory data of patients with T2DM manifesting heavy proteinuria who underwent renal biopsy from January 2014 to December 2017. RESULTS: According to renal biopsy, 220 patients were finally enrolled, including 109 cases diagnosed with DN alone (49.55%), 94 with NDRD alone (42.73%) and 17 with DN plus superimposed NDRD (7.73%). Multivariate analysis showed the significant risk factors for DN alone were age, duration of diabetes, presence of retinopathy, 24-h proteinuria, serum albumin and SBP. Presence of retinopathy achieved the highest overall diagnostic efficiency with the area under the curve of 0.852, sensitivity of 78.9% and specificity of 91.5%. The combined diagnosis with four indicators (duration of diabetes, retinopathy, SBP, and serum albumin) showed the area under the curve of 0.938, sensitivity of 88.1% and specificity of 87.2%. CONCLUSIONS: The prevalence of DN is high in patients with T2DM manifesting heavy proteinuria. Renal biopsy should be performed in diabetics in the atypical clinical scenario.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Rim/patologia , Proteinúria/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Rev Assoc Med Bras (1992) ; 65(9): 1155-1160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618330

RESUMO

OBJECTIVE: In this study, we aimed to analyze the relationship between serum uric acid (UA) and microalbuminuria as a marker of renal injury in type 2 diabetes mellitus. METHODS: A total of 100 patients with type 2 diabetes mellitus were enrolled in the study. Participants were divided into two groups according to the urinary microalbumin/creatinine ratio: diabetic nephropathy and non-nephropathy group. UA and microalbuminuria were compared between the study groups. RESULTS: Serum UA levels of diabetic nephropathy patients were significantly higher than those in the non-nephropathy group (UA in patients with diabetic nephropathy groups: 6.3 (1.82) mg/dl, UA in patients of the non-nephropathic group: 4.85 (1.92) mg/dl) (p<0.001). There was a correlation between microalbuminuria and UA (r=0.238). This correlation was statistically significant (p=0.017). CONCLUSION: UA levels may be an important predictor of nephropathy in diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Hiperuricemia/complicações , Ácido Úrico/sangue , Idoso , Albuminúria/urina , Biomarcadores/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Int J Mol Sci ; 20(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618817

RESUMO

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Tocotrienóis/química , Tocotrienóis/farmacologia , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Suplementos Nutricionais , Humanos , Estresse Oxidativo/efeitos dos fármacos , Tocoferóis/química , Tocoferóis/farmacologia , Vitamina E/administração & dosagem
11.
Life Sci ; 238: 116965, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629762

RESUMO

AIMS: Diabetic nephropathy (DN) is responsible for the occurrence of 30-47% of the incident cases of end-stage renal disease (ESRD) worldwide. DN is a chronic inflammatory disorder, which results from hyperglycemia-induced alterations and leads to renal fibrosis and ESRD. Toll like receptor-4 (TLR-4) participates in regulation of inflammatory response through controlling of innate immune system. P-Coumaric Acid (P-CA) is a natural hydroxycinnamic acid derivative and is widely present in vegetables, fruits, mushrooms and cereals. This study aimed to explore the renoprotective effect of P-CA, as anti-inflammatory and antioxidant natural compound, against experimental DN. METHODS: DN was induced by single intraperitoneal injection of streptozotocin (45 mg/kg) in rats. In kidney homogenate, levels of TLR-4, interleukin-6 (IL-6) and transforming growth factor ß1 (TGFß1) were measured using ELISA technique. Also, kidney collagen content was determined colorimetrically. KEY FINDINGS: Oral administration of P-CA (100 mg/kg) for 8 weeks significantly alleviated the DN. P-CA significantly reduced serum concentrations of glucose, creatinine, blood urea nitrogen (BUN) and reduced protein content in urine. Also, P-CA significantly increased superoxide dismutase (SOD) activity and significantly reduced kidney contents of malondialdehyde (MDA), TLR-4, IL-6, TGFß1 and collagen when compared with DN group. Moreover, P-CA significantly improved DN-induced histopathological abnormalities. SIGNIFICANCE: P-CA confers protection against the progression of DN. This renoprotective effect can be attributed to its ability to decrease the generation of inflammatory and fibrotic cytokines in addition to restoring oxidant/antioxidant balance through its ability to down-regulate TLR-4 activation.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Propionatos/farmacologia , Receptor 4 Toll-Like/metabolismo , Animais , Glicemia/metabolismo , Creatinina/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/genética
12.
Ren Fail ; 41(1): 899-906, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31552773

RESUMO

Objective: To investigate effects of combination use of leflunomide and benazepril on diabetic nephropathy (DN) both in vivo and in vitro. Methods: The streptozotocin (STZ) induced Sprague-Dawley rats were treated with leflunomide (15 mg/kg/d), benazepril (15 mg/kg/d) or both the two drugs. Fasting blood glucose (FBG) and renal function indexes including blood urea nitrogen (BUN), serum creatinine (Scr), and proteinuria and kidney/body weight ratio (KW/BW) were measured. HE staining was used for histological analysis. The rat glomerular mesangial cells (RMCs) were treated with high-glucose (150 mg/ml) and the leflunomide and benazepril with both concentrations of 50 µmol/l were used to treat the high-glucose induced cells. TUNEL assay was used for measurement of cell apoptosis. Western blotting was conducted to determine expression of nuclear factor Kappa B (NF-κB), transforming growth factor-ß (TGF-ß) and transient receptor potential canonical 6 (TRPC6). Results: The body weight was significantly lower and all indexes of FBG, BUN, Scr, proteinuria and KW/BW ratio, GFR, as well as inflammatory factors TNF-α and IL-6 were significantly increased in the DN group after STZ treatment for 4 weeks. The treatment with leflunomide, benazepril or the both dramatically reduced the above effects induced by STZ, and the alteration was the most significant in the combination group. Treatment of leflunomide and benazepril significantly reduced expression levels of NF-κB, TGF-ß and TRPC6 in renal tissues of DN rats as well as in high-glucose induced RMCs. It was also observed leflunomide and benazepril reduced high-glucose induced cell apoptosis of RMCs. Conclusion: The combination use of leflunomide and benazepril could improve the renal function and reduce the renal injury of DN rats and could reduce the levels of NF-κb, TGF-ß and TRPC6 in both DN rats and high-glucose induced RMCs.


Assuntos
Apoptose/efeitos dos fármacos , Benzazepinas/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Hiperglicemia/complicações , Leflunomida/farmacologia , Animais , Benzazepinas/uso terapêutico , Glicemia/análise , Linhagem Celular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Sinergismo Farmacológico , Quimioterapia Combinada , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Leflunomida/uso terapêutico , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade , Canais de Cátion TRPC/metabolismo , Fator de Crescimento Transformador beta/metabolismo
13.
Mol Med Rep ; 20(4): 3728-3734, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485651

RESUMO

Hyperglycemia promotes podocyte apoptosis and contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms of hyperglycemia­induced podocyte apoptosis remain unknown. Recent studies have implicated Src­associated substrate during mitosis of 68 kDa (Sam68) in various cellular processes including RNA metabolism, apoptosis, signal transduction. This study sought to examine the effect of Sam68 on high glucose (HG)­induced podocytes apoptosis, and the mechanism underlying this effect. Immortalized mouse podocytes were exposed to medium containing normal glucose, or HG and Sam68 siRNA, respectively. The expression of Sam68 in podocytes was determined by fluorescence quantitative PCR (qPCR), immunofluorescence and immunoblotting. The role of Sam68 in HG­induced podocyte apoptosis was further evaluated by inhibiting Sam68 expression by Sam68 siRNA and performing flow cytometry. The mRNA and protein expression of pro­apoptosis gene Bax and anti­apoptotic gene Bcl­2 were assessed by qRCR and immunoblotting. In the present study, it was first demonstrated that Sam68 was upregulated in a time and dose­dependent manner in in vitro HG­treated podocytes. Pretreatment with Sam68 siRNA markedly decreased nuclear Sam68 expression. Moreover, the effects of HG­induced apoptosis were also abrogated by Sam68 knockdown in cultured podocytes. Furthermore, HG increased Bax and decreased Bcl­2 protein expression in cultured podocytes, and this effect was blocked by Sam68 knockdown. The results of the present study revealed that Sam68 mediated HG­induced podocyte apoptosis, probably through the Bax/Bcl­2 signaling pathway, and thus may be a potential therapeutic target for DN.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Nefropatias Diabéticas/genética , Hiperglicemia/genética , Podócitos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas de Ligação a RNA/genética , Proteína X Associada a bcl-2/genética , Animais , Apoptose , Linhagem Celular , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Regulação para Baixo , Hiperglicemia/complicações , Hiperglicemia/patologia , Camundongos , Podócitos/metabolismo , Regulação para Cima
14.
Molecules ; 24(15)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390847

RESUMO

Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Avaliação Pré-Clínica de Medicamentos , Fibrose , Humanos , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Sistema Renina-Angiotensina
15.
Int J Health Plann Manage ; 34(3): 1013-1024, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31368138

RESUMO

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) in China was 11.6% in 2010. Chronic complications are the main diabetes-related cause of death and disability, accounting for more than 80% of the cost of diabetes treatment. Diabetic nephropathy (DN) is a common microvascular complication and is the second leading cause of end-stage renal failure in China. OBJECTIVE: We aimed to analyse the DN status among community-based T2DM patients and to explore risk factors for T2DM with DN. METHODS: This study was conducted in six communities of Shanghai. We administered a questionnaire, physical examination, and biochemical tests to 5078 patients with T2DM. Logistic regression and the classification tree model were used to analyse risk factors for T2DM with DN. RESULTS: In total, 1937 patients were diagnosed with DN (prevalence 38.4%). The logistic regression model indicated that course of disease more than 15 years, body mass index (BMI) greater than 24 kg/m2 , haemoglobin A1c (HbA1c) greater than 7.5%, fasting blood glucose (FBG) greater than 11.0 mmol/L, total cholesterol (TC), and high-density lipoprotein (HDL)-C control failure, hypertension, and diabetic retinopathy were risk factors for T2DM with DN (P < .05). The classification tree model identified seven risk factors (HbA1c, FBG, hypertension, postprandial blood glucose, BMI, triacylglycerol, and HDL), of which, HbA1c (cut-off point 7.45%), hypertension, and FBG showed the strongest association. CONCLUSION: This suggests that screening for DN based on HbA1c, FBG, and hypertension should be more extensively promoted by the government on a community level, more attention should be focused on patients' health management, and that patients should be educated on self-management.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Idoso , Glicemia/análise , Índice de Massa Corporal , China , Colesterol/sangue , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/complicações , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipertensão/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
16.
Diabetes Metab Syndr ; 13(4): 2457-2461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405660

RESUMO

AIM: To evaluate the role of advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) expression levels as predictors of vascular complications in uncontrolled type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional study was conducted on T2DM adults of both sexes who attended the outpatient service of Al-Karak Teaching Hospital, Jordan during the period from June 2017 to August 2018. Participants were categorized in two groups according to their glycemic control and the presence of reno-vascular complications. Twenty healthy subjects were recruited as control group. Blood sample was obtained from all participants and used for the assessment of FBG, HbA1c, serum AGEs and sRAGE, serum urea and creatinine; 24 h urine was also collected for the determination of urinary albumin. RESULTS: Diabetic subjects with vascular complication had a significantly higher serum AGEs 50.3 ±â€¯13 vs. 28.9 ±â€¯8 pg/ml) and AGEs/sRAGE ratio (0.058 ±â€¯0.02 vs. 0.037 ±â€¯0.02) associated with significantly lower serum sRAGE (868.7 ±â€¯50.8 vs. 912.8 ±â€¯294.3) compared to those with no complications. Serum AGEs and sRAGE showed weak negative and non-significant association in both groups of patients. However, the AGEs/sRAGE ration was inversely and significantly associated with the urinary albumin/creatinine ratio (r = - 0.51, P = 0.009) only in DM patients with reno-vascular complications. CONCLUSION: We found an association between AGEs/sRAGE ratio and urinary albumin/serum creatinine ratio in T2DM patients with reno-vascular complications; providing evidence that serum AGEs and sRAGE can be considered as predictors of vascular complications in uncontrolled T2DM patients.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Glicemia/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Diabetes Metab Syndr ; 13(4): 2661-2665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405691

RESUMO

AIM: diabetic patients are required for continuous monitoring programs hence continuous assessment of kidney function parameters is crucial. So, we aimed to determine the prevalence of Chronic Kidney Disease (CKD) and abnormal renal parameters, with poorly controlled type 2 diabetes mellitus pateints MATERIALS AND METHODS: A cross-sectional study was carried out at private health care centre. A total of 300 diabetic patients aged 18 years and above attended the clinic from February 2018 to Dec 2018 were included. Socio-demographic, clinical, and laboratory data were obtained from the medical records of patients. Statistical analysis was carried out using (SPSS, version 23). RESULTS: out of the 300 diabetes patients recruited 42% of patients with type 2 diabetes had abnormal Creatinine Serum levels and 22.3% had abnormal glomerular filtration rate (GFR). Abnormal albumin urine levels were found in 28.3% and 11.3% had abnormal creatinine in urine. Abnormal Albumin: Creatinine Ratios (Alb/Cr), were found in 23%. Of the total, 77% (n = 231) had normal Alb: Cr Ratio, 20% had risk of nephropathy and 9% had nephropathy. CONCLUSION: Current study revealed a high prevalence of abnormal renal parameters in patients with type 2 diabetes Mellitus. This necessitates the need for early and universal screening of renal functions. There is also an urgent demand for measures that target tight glycaemic, Vitamin D level and life style modifications is also required to all diabetic patients to achieve target value of HbA1C ≤ 7.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Glicemia/análise , Estudos Transversais , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Fatores de Risco , Emirados Árabes Unidos/epidemiologia
18.
EBioMedicine ; 47: 590-597, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405756

RESUMO

Glucose metabolism in the kidney is currently foremost in the minds of nephrologists, diabetologists and researchers globally, as a result of the outstanding success of SGLT2 inhibitors in reducing renal and cardiovascular disease in individuals with diabetes. However, these exciting data have come with the puzzling but fascinating paradigm that many of the beneficial effects on the kidney and cardiovascular system seem to be independent of the systemic glucose lowering actions of these agents. This manuscript places into context an area of research highly relevant to renal glucose metabolism, that of glycogen accumulation and metabolism in the diabetic kidney. Whether the glycogen that abnormally accumulates is pathological (the villain), is somehow protective (the hero) or is inconsequential (the bystander) is a research question that may provide insight into the link between diabetes and diabetic kidney disease.


Assuntos
Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Animais , Biomarcadores , Glicemia , Nefropatias Diabéticas/patologia , Gluconeogênese , Glicogênio/química , Doença de Depósito de Glicogênio/etiologia , Doença de Depósito de Glicogênio/metabolismo , Glicólise , Humanos , Redes e Vias Metabólicas
19.
BMC Endocr Disord ; 19(1): 84, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382952

RESUMO

BACKGROUND: In patients with diabetes mellitus, the urinary microalbumin-to-urine creatinine ratio (UACR) can not only predict the occurrence of diabetic nephropathy but also can be a risk factor for cardiovascular disease and renal function damage. Current studies on subclinical hypothyroidism (SCH) and UACR are mainly cross-sectional studies, and the results suggest that SCH is an independent risk factor for UACR. To further explore the longitudinal effect of SCH on UACR, we carried out this study. METHODS: This was a retrospective cohort study including 46 patients with type 2 diabetes mellitus and SCH in the Department of Endocrinology, The Affiliated Huai'an Hospital of Xuzhou Medical University from January 2013 to April 2018. At the same time, 96 patients with type 2 diabetes mellitus and euthyroid were chosen according to 1:2 approximately matched with age, sex and duration of diabetes mellitus. Univariate analysis, stratified analysis, and multiple linear regression analysis were used to investigate the effect of SCH on ΔUACR(ΔUACR = UACR after 1 year - baseline UACR) in patients with type 2 diabetes mellitus. RESULTS: There was no significant difference between the baseline UACR, (p > 0.05). However, the ΔUACR was significantly higher in SCH group than euthyroid group, as shown by univariate analysis, stratified analysis and multiple linear regression analysis (ß:-1.071, 95% CI: - 1.713--0.428), and the difference was statistically significant (all p < 0.05). CONCLUSION: SCH is associated with an increased UACR in type 2 diabetes mellitus patients. It is necessary to screen for thyroid function in type 2 diabetes mellitus and increase the follow-up frequency of UACR in patients with SCH.


Assuntos
Albuminúria/etiologia , Biomarcadores/análise , Creatinina/urina , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/etiologia , Hipotireoidismo/complicações , Adolescente , Adulto , Idoso , Albuminúria/diagnóstico , China/epidemiologia , Nefropatias Diabéticas/diagnóstico , Feminino , Seguimentos , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/patologia , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Life Sci ; 234: 116738, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398418

RESUMO

AIMS: Oxidative stress has been linked to the development and progression of diabetic nephropathy (DN). The present study evaluated whether the dipeptidyl peptidase-4 inhibitor sitagliptin attenuates glomerular lesions and oxidative stress evoked by chronic hyperglycemia, by a mechanism independent of insulin secretion and glycemia normalization. MAIN METHODS: A rat model of DN caused by streptozotocin injection was established and the effects of sitagliptin (5 mg/kg/day) were evaluated after two weeks of treatment. KEY FINDINGS: Sitagliptin treatment did not change body weight, glycemic and lipid profiles. However, histopathological observation revealed that sitagliptin attenuates diabetes-induced glomerular lesions on diabetic rats. Sitagliptin also ameliorated the increase in DPP-4 content and promoted the stabilization of GLP-1 in the diabetic kidney. Furthermore, sitagliptin treatment significantly attenuated the increase of free-radical formation and the decrease of antioxidant defenses, attenuating therefore the oxidative stress in the kidneys of diabetic animals. SIGNIFICANCE: The results suggest that sitagliptin treatment alleviates kidney oxidative stress in type 1 diabetic rats, which could play a key role in reducing the progression of DN.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfato de Sitagliptina/uso terapêutico , Animais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Ratos , Ratos Wistar , Fosfato de Sitagliptina/farmacologia
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