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1.
Zhonghua Yi Xue Za Zhi ; 101(10): 687-690, 2021 Mar 16.
Artigo em Chinês | MEDLINE | ID: mdl-33721944

RESUMO

Chronic kidney disease (CKD) in diabetes mellitus includes diabetic kidney disease (DKD), non-diabetic kidney disease (NDKD) or a combination of NDKD and DKD. The clinical and renal pathological manifestations of DKD in type 1 diabetes are different from those in type 2 diabetes. Renal biopsy histopathology is the gold standard for distinguishing DKD from NDKD. However, based on the same pathological diagnosis, DKD patients may still have different disease progression and prognosis due to individual differences in molecular biological mechanisms. Metabonomics, proteomics, transcriptomics and artificial intelligence offer hope for biomarkers to diagnose and predict the progress of DKD.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Inteligência Artificial , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Humanos , Insuficiência Renal Crônica/diagnóstico
2.
Zhonghua Yi Xue Za Zhi ; 101(10): 691-694, 2021 Mar 16.
Artigo em Chinês | MEDLINE | ID: mdl-33721945

RESUMO

Diabetic kidney disease (DKD) is the most common chronic complication of diabetes mellitus and the major cause of end stage renal disease (ESRD). Prediction, early diagnosis and evaluation of disease progression are crucial to improve the prognosis of DKD. Estimated glomerular filtration rate (GFR) and urinary albumin excretion rate (AER) are the main diagnostic biomarkers of DKD. However, the sensitivity and specificity are insufficient. In recent years, more and more attention has been paid to the value of novel biomarkers of DKD. This article reviews the clinical studies of novel biomarkers of DKD, in order to provide reference for clinical diagnosis and prognosis evaluation of DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Falência Renal Crônica , Biomarcadores , Nefropatias Diabéticas/diagnóstico , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Rim
3.
Medicine (Baltimore) ; 100(10): e25121, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725910

RESUMO

BACKGROUND: It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis. METHODS: We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint. RESULTS: Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84-0.94), MI (HR 0.91, 95% CI 0.84-0.99), CVD (HR 0.86, 95% CI 0.79-0.93), CVD or HHF (HR 0.77, 95% CI 0.73-0.82), HHF (HR 0.67, 95% CI 0.62-0.74), KFP (HR 0.63, 95% CI 0.56-0.70), and ACD (HR 0.88, 95% CI 0.83-0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88-1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size. CONCLUSIONS: Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/diagnóstico , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/epidemiologia , Infarto do Miocárdio/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Acidente Vascular Cerebral/epidemiologia , Causas de Morte , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Progressão da Doença , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
4.
Adv Exp Med Biol ; 1307: 521-551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32329028

RESUMO

Diabetes mellitus (DM) is the first cause of end stage chronic kidney disease (CKD). Animal models of the disease can shed light on the pathogenesis of the diabetic nephropathy (DN) and novel and earlier biomarkers of the condition may help to improve diagnosis and prognosis. This review summarizes the most important features of animal models used in the study of DN and updates the most recent progress in biomarker research.


Assuntos
Biomarcadores , Nefropatias Diabéticas , Modelos Animais de Doenças , Animais , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/diagnóstico , Rim
5.
Diab Vasc Dis Res ; 17(6): 1479164120971220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33371732

RESUMO

INTRODUCTION: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. MATERIALS AND METHODS: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)-dapagliflozin (n = 52) or empagliflozin (n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. RESULTS: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups (p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e' or left atrial volume index, decreased only in Group G at 36 months. CONCLUSIONS: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.


Assuntos
Albuminúria/tratamento farmacológico , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucosídeos/uso terapêutico , Incretinas/uso terapêutico , Rim/efeitos dos fármacos , Liraglutida/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/efeitos adversos , Humanos , Incretinas/efeitos adversos , Rim/fisiopatologia , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
6.
Nefrología (Madrid) ; 40(5): 543-551, sept.-oct. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-199036

RESUMO

BACKGROUND/AIMS: The most common adverse effect of baclofen, used for managing hiccups and spasticity, is neurotoxicity. As baclofen is primarily excreted by the kidneys, neurotoxicity is more likely to occur in patients with chronic kidney disease (CKD). We evaluated the risk factor for baclofen neurotoxicity and the recommended dosage for patients with severe CKD. METHODS: In this single-center retrospective study, we classified 401 patients with CKD as stage 4 (n=174), non-dialysis stage 5 (n=97), and on-dialysis (n=130). RESULTS: The prevalence of baclofen-induced neurotoxicity in patients with severe CKD was 7.0% (28 of 401 patients). There was no significant difference in the presence of neurotoxicity when the patients were classified as CKD stage 4, stage 5, and dialysis patients. There were significant differences in serum albumin levels and the presence of diabetic nephropathy between the patients with neurotoxicity and those without. The results from a multiple logistic regression analysis showed that serum albumin was independently associated with baclofen neurotoxicity (p = 0.007). The minimum daily dose for baclofen neurotoxicity was 10mg, 10mg, and 5mg in patients with CKD stages 4 and 5, and dialysis, respectively. CONCLUSIONS: In this study, the prevalence of baclofen-induced neurotoxicity in patients with severe CKD was 7.0%. Serum albumin was identified as an independent risk factor for neurotoxicity. We recommend initially administering a daily dose of 7.5mg for patients with severe CKD stages 4 and 5, and a daily dose of 2.5mg for patients receiving dialysis


ANTECEDENTES/OBJETIVOS: La neurotoxicidad es el efecto adverso más frecuente del baclofeno, un fármaco que se utiliza para tratar los espasmos y la espasticidad. Dado que el baclofeno se excreta principalmente a través de los riñones, es más probable que la neurotoxicidad se presente en pacientes con enfermedad renal crónica (ERC). Hemos evaluado el factor de riesgo para la neurotoxicidad por baclofeno y la dosis recomendada para pacientes con ERC grave. MÉTODOS: En este estudio retrospectivo unicéntrico, se clasificó a 401 pacientes con ERC en estadio 4 (n=174), estadio 5 sin diálisis (n=97) y en diálisis (n=130). RESULTADOS: La prevalencia de la neurotoxicidad inducida por baclofeno en pacientes con ERC grave fue del 7,0% (28 de 401 pacientes). No se observaron diferencias significativas en la presencia de neurotoxicidad al clasificar a los pacientes en ERC en estadio 4, estadio 5 y pacientes en diálisis. Se observaron diferencias significativas en los niveles de albúmina sérica y en la presencia de nefropatía diabética entre los pacientes con y sin neurotoxicidad. Los resultados de un análisis de regresión logística múltiple mostraron que la albúmina sérica estaba asociada de manera independiente a la neurotoxicidad por baclofeno (p = 0,007). La dosis diaria mínima para la neurotoxicidad por baclofeno fue de 10, 10 y 5mg en pacientes con ERC en estadio 4, estadio 5 y en diálisis, respectivamente. CONCLUSIONES: En este estudio, la prevalencia de la neurotoxicidad inducida por baclofeno en pacientes con ERC grave fue del 7,0%. Se identificó la albúmina sérica como un factor de riesgo independiente de neurotoxicidad. Recomendamos una administración inicial a una dosis diaria de 7,5mg en pacientes con ERC grave en estadios 4 y 5, y una dosis diaria de 2,5mg en pacientes que reciben diálisis


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Síndromes Neurotóxicas/epidemiologia , Baclofeno/efeitos adversos , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Insuficiência Renal/complicações , Fatores de Risco , Estudos Retrospectivos , Albumina Sérica/análise , Baclofeno/administração & dosagem , Baclofeno/toxicidade , Hipoalbuminemia/complicações
7.
Ther Umsch ; 77(7): 333-338, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32996426

RESUMO

Managing diabetic kidney disease Abstract. Diabetic kidney disease is a common complication of diabetes associated with an increased cardiovascular mortality and is the leading cause of end-stage renal disease. A heterogeneous set of pathological mechanisms drives the development and progression of diabetic kidney disease. A comprehensive diagnostic work-up and repeated reevaluation are needed since diabetic patients can suffer from other nephropathies with a clinical presentation similar to diabetic kidney disease. Screening, treatment of cardiovascular risk factors and the reduction of albuminuria, using renin-angiotensin-aldosterone system and sodium-dependent glucose transporter 2 inhibitors are crucial in the management of diabetic kidney disease.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/terapia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Inibidores do Transportador 2 de Sódio-Glicose , Albuminúria/diagnóstico , Albuminúria/terapia , Humanos , Sistema Renina-Angiotensina
8.
Internist (Berl) ; 61(10): 1094-1105, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32897404

RESUMO

BACKGROUND: The early detection and treatment of diabetic nephropathy (DN) is of crucial importance as patients with diabetes mellitus represent the largest proportion of patients on dialysis, with the highest morbidity and mortality. Currently, the first clinical sign of incipient DN is microalbuminuria, but its precision is not optimal. Many studies now report that proteins and peptides are new biomarkers in urine that primarily depict the pathophysiology of DN and thus allow for improved diagnosis of DN. OBJECTIVES: The presentation of new concepts for the early detection and treatment of DN for better patient management. MATERIAL AND METHODS: A systematic literature search was carried out. RESULTS: Many potential markers have been described in the search for new biomarkers to diagnose DN by urinary proteome analysis. However, many of these studies were not meaningful due to the small number of samples. This limitation led to inadequate validation of proteins that could not be confirmed as markers. However, the diagnostic benefit of CKD 273, a multimarker of 273 protein fragments, was sustainably demonstrated for the early diagnosis of DN. This multi-marker shows significant advantages in the precision of diagnosis and prognosis compared to albuminuria. Furthermore, many of its peptide markers map the molecular pathophysiology of DN. CONCLUSIONS: Clinical urinary proteome analysis shows great benefits and is already an appropriate tool for the early detection of incipient DN.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/urina , Proteoma/análise , Proteômica/métodos , Albuminúria/diagnóstico , Albuminúria/urina , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Diagnóstico Precoce , Humanos
9.
Diab Vasc Dis Res ; 17(7): 1479164120945910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32746630

RESUMO

BACKGROUND: The effect of interarm blood pressure difference on the development of diabetic retinopathy, proteinuria and chronic kidney disease remains unknown. We investigated to determine the impact of interarm blood pressure difference on the prevalence of diabetic retinopathy, proteinuria and chronic kidney disease in patients with type 2 diabetes. METHODS: The study included 563 patients with diabetes, who were evaluated with a simultaneous bilateral blood pressure measurement. The cutoff values for interarm blood pressure difference were 5, 10 and 15 mmHg. Logistic regression analysis was used to explore the relation between interarm blood pressure difference and diabetic retinopathy, proteinuria and chronic kidney disease. RESULTS: Diabetic patients with systolic interarm blood pressure difference ⩾5, ⩾10 and ⩾15 mmHg showed an increased risk of diabetic retinopathy [adjusted odds ratio = 1.48 (95% confidence interval = 1.01-2.18), odds ratio = 1.80 (95% confidence interval = 0.99-3.22), odds ratio = 2.29 (95% confidence interval = 1.00-5.23)] after adjustment. There were significant associations between interarm blood pressure difference ⩾5 and ⩾10 mmHg and proteinuria [odds ratio = 1.68 (95% confidence interval = 1.15-2.44), 1.89 (95% confidence interval = 1.05-3.37)]. CONCLUSION: The association between interarm blood pressure difference and the presence of diabetic retinopathy emerged even for systolic interarm blood pressure difference ⩾5 mmHg without interaction of systolic blood pressure. Systolic interarm blood pressure difference should be considered a surrogate marker for vascular complication in patients with type 2 diabetes.


Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Extremidade Superior/irrigação sanguínea , Idoso , Índice Tornozelo-Braço , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Seul/epidemiologia
10.
Vasc Health Risk Manag ; 16: 241-248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606720

RESUMO

Aim: Type 2 diabetes (T2D), as a major cause of morbidity and mortality, is predicted to have a prevalence of 629 million by 2045. As diabetic patients show considerable inter-individual variation in response to antidiabetic treatment, this study aimed to investigate the gene polymorphism of cytochrome P450 as well as the effectiveness and safety of glibenclamide and gliclazide for different genotypes of CYP2C9. Besides, the chronic side effects of T2D including retinal microvasculature complications or retinopathy and renal dysfunction due to nephropathy in different genotypes were considered. Patients and Methods: The participants including 80 T2D patients treated with glibenclamide or gliclazide were recruited from university hospitals of Ahvaz Jundishpur University of Medical Sciences, Ahvaz, in the southwest of Iran. Blood samples were collected from the patients at 2.5h after the morning dose of glibenclamide and 12h after the last dose of gliclazide. Genotyping from the extracted DNA was, then, performed using PCR-RFLP. The plasma level of glibenclamide and gliclazide was, in turn, measured by the reverse-phase high-pressure liquid chromatography. Results: The results showed that the wild-type allele, i.e., CYP2C9*1, occurred in the highest frequency (0.8), while the frequency rates of the mutant allele, i.e., CYP2C9*2 and CYP2C9*3, were 0.15 and 0.05, respectively. Moreover, no significant association was found between any of the genotypes as well as the clinical and biochemical characteristics of the patients. The findings also showed that the plasma level of sulfonylureas (i.e., glibenclamide and gliclazide) was the highest in the patients with the CYP2C9*3 allele. It was also found that 75.9% of the patients with variant genotypes had experienced hypoglycemia events. Furthermore, in the absence of wild type allele, a significant increase was observed in retinopathy (p=0.039) and nephropathy (p=0.05). Conclusion: The findings can provide guidelines for the optimal management of the treatment protocols with sulfonylurea intended to control the T2D complications.


Assuntos
Glicemia/efeitos dos fármacos , Citocromo P-450 CYP2C9/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/genética , Retinopatia Diabética/genética , Gliclazida/uso terapêutico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Variantes Farmacogenômicos , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/diagnóstico , Retinopatia Diabética/diagnóstico , Feminino , Frequência do Gene , Gliclazida/efeitos adversos , Gliclazida/sangue , Glibureto/efeitos adversos , Glibureto/sangue , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/genética , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
11.
Saudi Med J ; 41(7): 690-697, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32601635

RESUMO

OBJECTIVES: To evaluate 2 renal tubular enzymes; urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary N-acetyl-beta-D-glucosaminidase (uNAG), and serum Cystatin C as candidate biomarkers for early diagnosis of early stage of diabetic nephropathy (DB) in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia during the period between  May 2017 and May 2018 and was conducted on 86 patients with T2DM. Patients were classified according to their albumin/creatinine ratio (ACR) into 3 groups; a normal albuminuria group with ACR less than 30 mg/g creatinine, a moderately increased albuminuria group with ACR: 30-299 mg/g creatinine, and a severely increased albuminuria group with ACR ≥300 mg/g.  Healthy adults were recruited as a control group. Urine uNGAL, uNAG, and serum Cystatin C were measured in all patients. RESULTS: Compared with healthy control, diabetic patients with normal albuminuria excreted significantly higher levels of uNGAL (p less than 0.001). In addition, significantly elevated uNGAL, uNAG and cystatin C levels were observed in moderately increased albuminuria and severely increased albuminuria groups when compared to the control and normoalbuminuric groups (p less than 0.001). urinary neutrophil gelatinase-associated lipocalin, urinary N-acetyl-beta-D-glucosaminidase and Cystatin C showed a positive correlation with fasting blood glucose (FBG), HbA1c, duration of diabetes, urea, creatinine, and ACR. CONCLUSION: Our results indicated that uNGAL could be a sensitive biomarker for early renal dysfunction in diabetic patients while uNAG and serum Cystatin C might have prognostic value.


Assuntos
Cistatina C/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Lipocalina-2/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
12.
Nutr Metab Cardiovasc Dis ; 30(10): 1723-1731, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32636121

RESUMO

AIMS: To investigate the associations between Lp(a), Apo A1, Apo B, and Apo B/Apo A1 ratio with micro- and macrovascular complications of diabetes. METHODS AND RESULTS: In this case-cohort study, 1057 patients with type 2 diabetes (T2DM) were followed in the diabetes clinic of Vali-Asr Hospital from 2014 to 2019. The association between serum Lp (a) and apolipoproteins with cardiovascular disease (CVD), neuropathy, and nephropathy were assessed by using binary regression analysis. The ROC curve analysis was used to evaluate the predictive properties of proteins. Youden index was used to calculate cutoff values. Among patients with T2DM, 242, 231, and 91 patients developed CVD, neuropathy, and nephropathy, respectively. The serum Lp (a) level was positively correlated with the development of all three. (P-values = 0.022, 0.042, and 0.038, respectively). The Apo A1 level was negatively correlated with nephropathy. Among the biomarkers, Lp(a) had the highest AUC for prediction of CVD, neuropathy, and nephropathy. Calculated cutoff values of Lp(a), and Apo A1 levels were higher than the standard cutoff values. CONCLUSION: Serum level of Lp(a) is a predictor for CVD, neuropathy, and nephropathy. Based on the calculated cutoff values in patients with T2DM, we should consider diabetic complications at higher levels of Lp(a).


Assuntos
Apolipoproteína A-I/sangue , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/epidemiologia , Dislipidemias/sangue , Lipoproteína(a)/sangue , Idoso , Apolipoproteína B-100/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/diagnóstico , Nefropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/diagnóstico , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco
13.
Cardiovasc Diabetol ; 19(1): 105, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631323

RESUMO

BACKGROUND: To assess the associations of various HbA1c measures, including a single baseline HbA1c value, overall mean, yearly updated means, standard deviation (HbA1c-SD), coefficient of variation (HbA1c-CV), and HbA1c variability score (HVS), with microvascular disease (MVD) risk in patients with type 2 diabetes. METHODS: Linked data between National Cheng Kung University Hospital and Taiwan's National Health Insurance Research Database were utilized to identify the study cohort. The primary outcome was the composite MVD events (retinopathy, nephropathy, or neuropathy) occurring during the study follow-up. Cox model analyses were performed to assess the associations between HbA1c measures and MVD risk, with adjustment for patients' baseline HbA1c, demographics, comorbidities/complications, and treatments. RESULTS: In the models without adjustment for baseline HbA1c, all HbA1c variability and mean measures were significantly associated with MVD risk, except HVS. With adjustment for baseline HbA1c, HbA1c-CV had the strongest association with MVD risk. For every unit of increase in HbA1c-CV, the MVD risk significantly increased by 3.42- and 2.81-fold based on the models without and with adjustment for baseline HbA1c, respectively. The associations of HbA1c variability and mean measures with MVD risk in patients with baseline HbA1c < 7.5% (58 mmol/mol) were stronger compared with those in patients with baseline HbA1c ≥ 7.5% (58 mmol/mol). CONCLUSIONS: HbA1c variability, especially HbA1c-CV, can supplement conventional baseline HbA1c measure for explaining MVD risk. HbA1c variability may play a greater role in MVD outcomes among patients with relatively optimal baseline glycemic control compared to those with relatively poor baseline glycemic control.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Hemoglobina A Glicada/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Retinopatia Diabética/sangue , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia , Fatores de Tempo
14.
Cardiovasc Diabetol ; 19(1): 72, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493344

RESUMO

BACKGROUND: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP4 inhibitors such as linagliptin (LG) on CVD risk, in patients with T2DM with established CKD has not been established. Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) population. METHODS: 31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 diabetes subjects (30-70 years old), HbA1c of 6.5-10%, CKD Stage 1-3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value < 0.05 considered significant. RESULTS: A double positive CD34/CD184 cell count had a statistically significant increase (p < 0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p < 0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p < 0.04). Urinary exosome protein examining podocyte health (podocalyxin, Wilms tumor and nephrin) showed reduction or improvement. CONCLUSIONS: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34 + progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks. Trial Registration Number NCT02467478 Date of Registration: 06/08/2015.


Assuntos
Antígenos CD34/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Células Progenitoras Endoteliais/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Linagliptina/uso terapêutico , Metformina/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Biomarcadores/sangue , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , District of Columbia , Método Duplo-Cego , Quimioterapia Combinada , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Linagliptina/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Receptores CXCR4/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do Tratamento
15.
Cardiovasc Diabetol ; 19(1): 98, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590982

RESUMO

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Rim/efeitos dos fármacos , Insuficiência Renal/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Regulação para Baixo , Humanos , Rim/fisiopatologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/epidemiologia , Insuficiência Renal/fisiopatologia , Medição de Risco , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
16.
Drugs Aging ; 37(8): 567-584, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32495289

RESUMO

Age-related metabolic and renal changes predispose older people to an increased risk of diabetes mellitus and diabetic kidney disease, respectively. As the prevalence of the ageing population is increasing, because of increased life expectancy, the prevalence of older people with diabetic kidney disease is likely to increase. Diabetic kidney disease is associated with an increased risk of adverse outcomes and increased costs to healthcare systems. The management includes promotion of a healthy lifestyle and control of cardiovascular risk factors such as hyperglycaemia, hypertension and dyslipidaemia. Older people are a heterogeneous group of people from a community-living fit and independent person to a fully dependent individual residing in a care home. Therefore, management in this age group should be based on a patient's functional level adopting tight metabolic control in the fit individual and relaxed targets in the frail person. However, despite the maximum available therapy, a significant number of patients with diabetic kidney disease still progress to renal failure and experience adverse cardiac outcomes. Therefore, future research is required to explore methods of early detection of diabetic kidney disease and to investigate novel therapeutic interventions to further improve the outcomes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Dislipidemias/tratamento farmacológico , Idoso Fragilizado , Hipertensão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Dislipidemias/complicações , Humanos , Hipertensão/complicações , Masculino
17.
Cardiovasc Diabetol ; 19(1): 85, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534578

RESUMO

BACKGROUND: Type 2 diabetes (T2D) is associated with renal impairment and vascular endothelial dysfunction. Therefore, this pathological connection is an important therapeutic target. Recent cardiovascular and renal outcome trials demonstrated that sodium glucose cotransporter 2 inhibitors (SGLT2is) consistently reduced the risks of cardiovascular and renal events and mortality in patients with T2D and various other background risks including chronic kidney disease (CKD). However, the precise mechanisms by which SGLT2is accords these therapeutic benefits remain uncertain. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of endothelial dysfunction in patients with T2D and CKD. METHODS: The PROCEED trial is an investigator-initiated, prospective, multicenter, open-label, randomized-controlled trial. The target sample size is 110 subjects. After they furnish informed consent and their endothelial dysfunction is confirmed from their decreased reactive hyperemia indices (RHI), eligible participants with T2D (HbA1c, 6.0-9.0%) and established CKD (30 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 60 and/or ≥ urine albumin-to-creatinine ratio 30 mg/g Cr) will be randomized (1:1) to receive either 50 mg ipragliflozin daily or continuation of background treatment (non-SGLT2i). The primary endpoint is the change in RHI from baseline after 24 weeks. To compare the treatment effects between groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for HbA1c (< 7.0% or ≥ 7.0%), age (< 70 y or ≥ 70 y), RHI (< 1.67 or ≥ 1.67), eGFR (< 45 mL/min/1.73 m2 or ≥ 45 mL/min/1.73 m2), and smoking status. Prespecified responder analyses will be also conducted to determine the proportions of patients with clinically meaningful changes in RHI at 24 weeks. DISCUSSION: PROCEED is the first trial to examine the effects of ipragliflozin on endothelial dysfunction in patients with T2D and CKD. This ongoing trial will establish whether endothelial dysfunction is a therapeutic target of SGLT2is in this population. It will also provide deep insights into the potential mechanisms by which SGLT2is reduced the risks of cardiovascular and renal events in recent outcome trials. Trial registration Unique Trial Number, jRCTs071190054 (https://jrct.niph.go.jp/en-latest-detail/jRCTs071190054).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiofenos/uso terapêutico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Endotélio Vascular/fisiopatologia , Glucosídeos/efeitos adversos , Humanos , Japão/epidemiologia , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Tiofenos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
18.
Cardiovasc Diabetol ; 19(1): 82, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534580

RESUMO

BACKGROUND: Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. METHODS: Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED). RESULTS: In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00-119.91 for the primary outcome; HR, 4.12; 95% CI 1.37-12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14-9.17). CONCLUSIONS: PED can independently predict future cardiovascular events among diabetic patients with albuminuria.


Assuntos
Albuminúria/epidemiologia , Nefropatias Diabéticas/epidemiologia , Endotélio Vascular/fisiopatologia , Doença Arterial Periférica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso , Albuminúria/diagnóstico , Albuminúria/mortalidade , Albuminúria/terapia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Manometria , Pessoa de Meia-Idade , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/terapia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Seul/epidemiologia , Fatores de Tempo
19.
Cardiovasc Diabetol ; 19(1): 50, 2020 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359350

RESUMO

BACKGROUND: The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes. METHODS: BP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index. RESULTS: Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%). CONCLUSIONS: Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/epidemiologia , Idoso , Brasil/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/mortalidade , Neuropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Humanos , Incidência , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sístole , Fatores de Tempo
20.
Am J Kidney Dis ; 76(2): 295-297, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32362418
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