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1.
Clin Exp Nephrol ; 25(7): 727-750, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33656638

RESUMO

BACKGROUND: To suppress increases in kidney failure and cardiovascular disease due to lifestyle-related diseases other than diabetes, early intervention is desirable. We examined whether microalbuminuria could be predicted from proteinuria. METHODS: The participants consisted of adults who exhibited a urinary protein-to-creatinine ratio (uPCR) of < 0.5 g/gCr and an eGFR of ≥ 15 ml/min/1.73 m2 in their spot urine at their first examination for lifestyle-related disease. Urine was tested three times for each case, with microalbuminuria defined as a urinary albumin-to-creatinine ratio (uACR) of 30-299 mg/gCr, at least twice on three measurements. Youden's Index was used as an index of the cut-off value (CO) according to the ROC curve. RESULTS: A single uPCR was useful for differentiating normoalbuminuria and micro- and macroalbuminuria in patients with non-diabetic lifestyle-related diseases. Regarding the GFR categories, the CO of the second uPCR was 0.09 g/gCr (AUC 0.89, sensitivity 0.76, specificity 0.89) in G1-4 (n = 197) and 0.07 g/gCr (AUC 0.92, sensitivity 0.85, specificity 0.88) in G1-3a (n = 125). Using the sum of two or three uPCR measurements was more useful than a single uPCR for differentiating microalbuminuria in non-diabetic lifestyle disease [CO, 0.16 g/gCr (AUC 0.91, sensitivity 0.85, specificity 0.87) and 0.23 g/gCr (AUC 0.92, sensitivity 0.88, specificity 0.84), respectively]. CONCLUSION: Microalbuminuria in Japanese individuals with non-diabetic lifestyle-related diseases can be predicted from the uPCR, wherein the CO of the uPCR that differentiates normoalbuminuria and micro- and macroalbuminuria was 0.07 g/gCr for G1-3a, while that in G3b-4 was 0.09 g/gCr.


Assuntos
Albuminúria/urina , Complicações do Diabetes/urina , Insuficiência Renal Crônica/urina , Idoso , Creatinina/urina , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade
2.
Ups J Med Sci ; 121(3): 174-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27321055

RESUMO

AIM: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes. METHODS: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7-13.4 years), 33 participants died of cardiovascular causes. RESULTS: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03-2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk. CONCLUSION: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.


Assuntos
Biomarcadores/urina , Doenças Cardiovasculares/urina , Diabetes Mellitus/urina , Injúria Renal Aguda/urina , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Cistatina C/urina , Complicações do Diabetes/mortalidade , Complicações do Diabetes/urina , Diabetes Mellitus/mortalidade , Nefropatias Diabéticas/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Túbulos Renais/metabolismo , Lipocalina-2/urina , Estudos Longitudinais , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
3.
Medicine (Baltimore) ; 95(17): e3423, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27124027

RESUMO

The objective of this study was to examine the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with hearing impairment among diabetic adults in Korea. The study was based on data from Korea National Health and Nutrition Examination Survey 2011 to 2012. Participants were 1206 diabetic adults, aged over 19 years, who completed audiometric testing supervised by nationally certified clinicians. Hearing impairment was defined in three grades: no hearing impairment (pure-tone average 0-25 dB), slight hearing impairment (26-40 dB), and disabling hearing impairment (>40 dB) in the better ear at frequencies 0.5, 1, 2, 3, 4 and 6 kHz. Using logistic regression, risk of hearing impairment was assessed after having controlled for confounding factors. Higher levels of ACR and lower levels of eGFR correlated with an increase in percentage of disabling hearing impairment both unilaterally and bilaterally (P < 0.001). Controlling for possible confounding covariates, odds ratios for hearing impairment showed tendency to increase in higher ACR groups (P for trend = 0.029). Similar pattern was examined between eGFR and hearing impairment (P for trend = 0.006). Odds ratios were 1.981 (1.146, 3.424) for ACR Q4 and 2.773 (1.286, 5.983) for eGFR < 60 mL/min. Fall in eGFR and rise in ACR correlated with severity of hearing impairment. The association existed independently of age, sex, body mass index (BMI), smoking, drinking, exercise, new onset of diabetes, education, income, mental stress, noise exposure, and metabolic syndrome.


Assuntos
Albuminúria/diagnóstico , Albuminúria/urina , Creatinina/urina , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/urina , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/urina , Taxa de Filtração Glomerular/fisiologia , Perda Auditiva/diagnóstico , Perda Auditiva/urina , Adulto , Comorbidade , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco , Estatística como Assunto
4.
Can Vet J ; 57(4): 382-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27041755

RESUMO

A 12-year-old female dog with a 3-month history of poor response to diabetes treatment had an acute worsening of symptoms, including weakness and blindness. The dog had elevated blood glucose, alkaline phosphatase and urea concentration, hyposthenuria, glycosuria, hematuria, and pyuria. Escherichia coli was isolated from the urine. Radiographs and ultrasound examination showed that the dog had unilateral emphysematous pyelitis and concurrent cystitis associated with vesicoureteral reflux.


Pyélite emphysémateuse et cystite associées au reflux vésico-urétéral chez une chienne diabétique. Une chienne âgée de 12 ans avec une anamnèse de 3 mois de mauvaise réponse au traitement du diabète a présenté un aggravement aigu des symptômes, y compris de la faiblesse et de la cécité. La chienne avait une glycémie élevée, ainsi que des concentrations sériques élevées de la phosphatase alcaline et d'urée, de l'hyposthénurie, de la glycosurie, de l'hématurie et de la pyurie. Escherichia coli a été isolé de l'urine. Des radiographies et des échographies ont montré que la chienne était atteinte de pyélite emphysémateuse unilatérale et de cystite concomitante associées au reflux vésico-urétéral.(Traduit par Isabelle Vallières).


Assuntos
Complicações do Diabetes/veterinária , Enfisema/veterinária , Pielocistite/veterinária , Refluxo Vesicoureteral/veterinária , Animais , Complicações do Diabetes/urina , Cães , Enfisema/complicações , Escherichia coli/isolamento & purificação , Feminino , Pielocistite/etiologia , Pielocistite/urina , Refluxo Vesicoureteral/complicações , Refluxo Vesicoureteral/urina
5.
Klin Lab Diagn ; 61(8): 484-9, 2016 Aug.
Artigo em Russo | MEDLINE | ID: mdl-30601640

RESUMO

The diabetes mellitus and arterial hypertension are among the most significant pathologies conditioning disorder of excretion of protein with urine. These very diseases are mostly dangerous for kidneys. Therefore, important significance has the search of early manifestations of damage of kidneys in patients with these diseases. The microalbuminuria is one of early manifestations of affection of kidneys in patients with diabetes mellitus and arterial hypertension. Only this early (pre-clinical) stage of affection of kidneys is the only reversible one in case of prescription of medicinal therapy. Nowadays, factually all applied diagnostic test-systems for detection ofmicroalbuminuria are based on immunological half-quantitative and quantitative detection of concentration of human serum albumin in urine. In this study was applied new recombinant human serum poly-peptide A3 from strain of streptococcus group G isolated from cow milk. The human serum albumin-binding capacity of poly-peptide A3 was analyzed in comparison with poly-peptide A2. Previously, recombinant human serum albumin-binding poly-peptide A2 was primarily applied in test-system for detection of microalbuminuria instead of commonly used antibodies. The analysis of 'human serum albumin-binding capacity of recombinant human serum poly-peptide A3 and A2 demonstrated that both of them can interact with human serum albumin in solution and adsorbed condition. This characteristic permitted applying poly-peptide A3 in immobilized form in qualitative test-system for detecting microalbuminuria. The actual study also propose specific and sensitive technique of screening and monitoring of patients with diabetes mellitus and arterial hypertension. The mentioned technique used tagged human serum albumin-binding polypeptide A3 combined with microchip technology. The comparison of test-systems using recombinant poly-peptides A3 and A2 established that application of poly-peptide A3 in test-system permits to detect more precisely concentration of human serum albumin in urine samples. The test-system of this kind was successfully implemented for both detection and qualitative identification of microalbuminuria in patients with diabetes mellitus and arterial hypertension.


Assuntos
Albuminúria/urina , Complicações do Diabetes/urina , Hipertensão/urina , Nefropatias/urina , Animais , Bovinos , Humanos , Hipertensão/patologia , Rim/química , Rim/patologia , Nefropatias/etiologia , Peptídeos/química , Peptídeos/genética , Ligação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Albumina Sérica Humana/química , Albumina Sérica Humana/genética , Streptococcus/química , Streptococcus/genética
6.
PLoS One ; 8(8): e69454, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23936331

RESUMO

Abnormal urinary excretion of betaine has been demonstrated in patients with diabetes or metabolic syndrome. We aimed to identify the main predictors of excretion in cardiovascular patients and to make initial assessment of its feasibility as a risk marker of future diabetes development. We used data from 2396 patients participating in the Western Norway B-vitamin Intervention Trial, who delivered urine and blood samples at baseline, and in the majority at two visits during follow-up of median 39 months. Betaine in urine and plasma were measured by liquid-chromatography-tandem mass spectrometry. The strongest determinants of urinary betaine excretion by multiple regression were diabetes mellitus, age and estimated glomerular filtration rate; all p<0.001. Patients with diabetes mellitus (n = 264) had a median excretion more than three times higher than those without. We found a distinct non-linear association between urinary betaine excretion and glycated hemoglobin, with a break-point at 6.5%, and glycated hemoglobin was the strongest determinant of betaine excretion in patients with diabetes mellitus. The discriminatory power for diabetes mellitus corresponded to an area under the curve by receiver-operating characteristics of 0.82, and betaine excretion had a coefficient of reliability of 0.73. We also found a significant, independent log-linear relation between baseline betaine excretion and the risk of developing new diabetes during follow-up. The good discriminatory power for diabetes, high test-retest stability and independent association with future risk of new diabetes should motivate further investigation on the role of betaine excretion in risk assessment and long-term follow-up of diabetes mellitus.


Assuntos
Betaína/urina , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/urina , Complicações do Diabetes/complicações , Complicações do Diabetes/urina , Diabetes Mellitus/diagnóstico , Idoso , Betaína/sangue , Biomarcadores/sangue , Biomarcadores/urina , Glicemia/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/prevenção & controle , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Vitamínico B/farmacologia
7.
Diabetes Care ; 35(4): 879-86, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22338108

RESUMO

OBJECTIVE: To assess the cardiovascular risk of diabetic subjects with chronic kidney disease (CKD) based on different estimated glomerular filtration rate (eGFR) equations and to evaluate which definition of CKD best improves cardiovascular risk prediction of the Framingham Cardiovascular Risk Score (Framingham-CV-RS). RESEARCH DESIGN AND METHODS: CKD was defined as eGFR <60 mL/min/1.73 m(2), estimated by the creatinine-based Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and a cystatin C-based equation (CKD-CysC). Cox regression was used to estimate hazard ratios (HRs) of subjects with CKD for incident cardiovascular events in a cohort of 1,153 individuals with diabetes (baseline age 50-74 years). Furthermore, the CKD definitions were added individually to a reference model comprising the Framingham-CV-RS variables and HbA(1c), and measures of model discrimination and reclassification were assessed. RESULTS: During 5 years of follow-up, 95 individuals had a primary cardiovascular event. Crude HRs were increased for all CKD definitions. However, after adjusting for established cardiovascular risk factors, HRs for both creatinine-based CKD definitions were attenuated to point estimates of 1.03, whereas the HRs for the cystatin C-based CKD definition remained significantly increased (HR 1.75 [95% CI 1.07-2.87]). Extension of the reference model by the different CKD definitions resulted in an increase in the c statistic only when adding CKD-CysC (from 0.638 to 0.644) along with a net reclassification improvement of 8.9%. CONCLUSIONS: Only the cystatin C-based CKD definition was an independent risk predictor for cardiovascular events in our diabetic study cohort and indicated a potentially better clinical utility for cardiovascular risk prediction than creatinine-based equations.


Assuntos
Doenças Cardiovasculares/diagnóstico , Creatinina/análise , Cistatina C/análise , Complicações do Diabetes/diagnóstico , Testes de Função Renal/métodos , Rim/fisiologia , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/urina , Creatinina/sangue , Creatinina/urina , Cistatina C/sangue , Cistatina C/urina , Complicações do Diabetes/sangue , Complicações do Diabetes/etiologia , Complicações do Diabetes/urina , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
8.
PLoS One ; 6(7): e21666, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21747945

RESUMO

BACKGROUND: Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these. METHODOLOGY: Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment. PRINCIPAL FINDINGS: Plasma betaine negatively correlated with triglyceride (Spearman's r(s) = -0.22, p<0.0001) and non-high-density lipoprotein cholesterol (r(s) = -0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin. CONCLUSION: Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk.


Assuntos
Síndrome Coronariana Aguda/sangue , Betaína/sangue , Lipídeos/sangue , Síndrome Coronariana Aguda/urina , Idoso , Idoso de 80 Anos ou mais , Betaína/metabolismo , Betaína/urina , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/urina , Suplementos Nutricionais , Feminino , Humanos , Hipolipemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Sarcosina/análogos & derivados , Sarcosina/sangue , Sarcosina/metabolismo
9.
Nephron Clin Pract ; 117(2): c160-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20699621

RESUMO

BACKGROUND: Type IV collagen is one of the major components of basement membrane. In diabetic nephropathy, it is already known that urinary excretion of type IV collagen increases with the disease progression. However, in nondiabetic kidney disease, urinary type IV collagen (u-IVc) levels have not been extensively investigated. The aim of this study was to evaluate u-IVc levels in various nephropathies except diabetic nephropathy. METHODS: u-IVc levels were measured cross-sectionally from 527 biopsy-proven nondiabetic renal disease patients at tertiary care hospitals by one-step sandwich enzyme immunoassay. RESULTS: On simple regression analyses, u-IVc levels had positive correlation with age, blood pressure, urinary protein (u-Prot), urinary ß(2) microglobulin, urinary N-acetyl-ß-D-glucosaminidase, HbA(1)c, and selectivity index (SI), while u-IVc had negative correlation with eGFR and serum albumin. Multiple regression analyses revealed that u-IVc was positively correlated with u-Prot, HbA(1)c and SI. Among biopsy-proven nondiabetic nephropathies, elevation of u-IVc was distinctively observed in membranous nephropathy and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. CONCLUSION: u-IVc levels were elevated with the increase in u-Prot, HbA(1)c and SI. In addition, among nondiabetic kidney disease, elevation of u-IVc was observed in patients with membranous nephropathy and ANCA, which might reflect the thickening of basement membrane or severe kidney damage.


Assuntos
Colágeno Tipo IV/urina , Nefropatias/epidemiologia , Nefropatias/urina , Adolescente , Biomarcadores/urina , Criança , Estudos Transversais , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/urina , Feminino , Humanos , Japão/epidemiologia , Masculino , Prevalência , Medição de Risco , Fatores de Risco , Adulto Jovem
10.
Curr Diab Rep ; 10(1): 37-42, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20425065

RESUMO

Currently used measures to assess kidney function and injury are largely inadequate. Markers such as serum creatinine, formulas to estimate glomerular filtration rate, cystatin C, and proteinuria largely identify an underlying disease process that is well established. Thus, there has been a recent effort to identify new biomarkers that reflect kidney function, early injury, and/or repair that ultimately can relate to progression or regression of damage. Several biomarkers emerged recently that are able to detect kidney damage earlier than is currently possible with traditional biomarkers such as serum creatinine and proteinuria. Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease. In this article, we focus on the applications of these biomarkers in disease.


Assuntos
Biomarcadores/metabolismo , Complicações do Diabetes/metabolismo , Hipertensão/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Albuminúria/sangue , Albuminúria/complicações , Albuminúria/fisiopatologia , Albuminúria/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Complicações do Diabetes/sangue , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/urina , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/sangue , Hipertensão/urina , Falência Renal Crônica/fisiopatologia
12.
Cardiovasc Drugs Ther ; 23(5): 395-401, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19653086

RESUMO

PURPOSE: Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion. METHODS: We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups. RESULTS: Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p < 0.00001 in some studies with n < 10. Of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p < 0.00001). In elderly (>65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013). CONCLUSIONS: Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.


Assuntos
Betaína/urina , Ácido Clofíbrico/efeitos adversos , Homocisteína/sangue , Hipolipemiantes/efeitos adversos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/urina , Idoso , Ácido Clofíbrico/uso terapêutico , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/urina , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Masculino , S-Adenosilmetionina/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/urina
13.
Mol Cell Proteomics ; 8(9): 2145-58, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19497846

RESUMO

Diabetes mellitus is estimated to affect approximately 24 million people in the United States and more than 150 million people worldwide. There are numerous end organ complications of diabetes, the onset of which can be delayed by early diagnosis and treatment. Although assays for diabetes are well founded, tests for its complications lack sufficient specificity and sensitivity to adequately guide these treatment options. In our study, we employed a streptozotocin-induced rat model of diabetes to determine changes in urinary protein profiles that occur during the initial response to the attendant hyperglycemia (e.g. the first two months) with the goal of developing a reliable and reproducible method of analyzing multiple urine samples as well as providing clues to early markers of disease progression. After filtration and buffer exchange, urinary proteins were digested with a specific protease, and the relative amounts of several thousand peptides were compared across rat urine samples representing various times after administration of drug or sham control. Extensive data analysis, including imputation of missing values and normalization of all data was followed by ANOVA analysis to discover peptides that were significantly changing as a function of time, treatment and interaction of the two variables. The data demonstrated significant differences in protein abundance in urine before observable pathophysiological changes occur in this animal model and as function of the measured variables. These included decreases in relative abundance of major urinary protein precursor and increases in pro-alpha collagen, the expression of which is known to be regulated by circulating levels of insulin and/or glucose. Peptides from these proteins represent potential biomarkers, which can be used to stage urogenital complications from diabetes. The expression changes of a pro-alpha 1 collagen peptide was also confirmed via selected reaction monitoring.


Assuntos
Complicações do Diabetes/urina , Modelos Animais de Doenças , Peptídeos/urina , Proteoma/análise , Sequência de Aminoácidos , Animais , Colágeno/química , Colágeno/urina , Colágeno Tipo I , Masculino , Espectrometria de Massas , Dados de Sequência Molecular , Peptídeos/química , Análise de Componente Principal , Proteoma/química , Controle de Qualidade , Ratos , Ratos Endogâmicos F344 , Reprodutibilidade dos Testes , Coloração e Rotulagem
14.
Diabetologia ; 51(12): 2318-24, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18839132

RESUMO

AIMS/HYPOTHESIS: The involvement of chronic inflammation in albuminuria and renal function was investigated in a cross-sectional study of 320 type 2 diabetic Chinese patients from the Singapore Diabetes Cohort Study. METHODS: Plasma levels of TNF-alpha and its two cellular receptors and of IL-6 and C-reactive protein (CRP) were measured. A composite TNF-alpha score was extracted using principal component analysis. Multiple linear regression analysis was implemented to evaluate the relationship between log( e ) (ln) albumin:creatinine ratio (ACR) and estimated GFR (eGFR) with the inflammatory variables and other clinical covariates. A Bonferroni correction was applied based on the total number of variables entered into regression analyses. RESULTS: ln ACR was significantly associated with TNF-alpha score independently of eGFR even after a Bonferroni correction. TNF-alpha score was also significantly associated with eGFR independently of ln ACR even after correction for multiple testing. These findings were similar when the individual molecules of the TNF-alpha system were analysed separately instead of using the composite TNF-alpha score. No association was observed for IL-6 and CRP with either renal trait. Diabetes duration was a significant predictor for ln ACR but not eGFR. Conversely, age was significantly associated with eGFR but not ln ACR. CONCLUSIONS/INTERPRETATION: Activation of the TNF-alpha system may potentially exert independent effects on ln ACR and eGFR in type 2 diabetes. Because of the study design, one may also consider the possibility that changes in these renal traits may conversely be responsible for such an inflammatory response.


Assuntos
Albuminúria/fisiopatologia , Albuminúria/urina , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/urina , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/urina , Fator de Necrose Tumoral alfa/urina , Idoso , Albuminúria/complicações , Albuminúria/etnologia , Biomarcadores/sangue , Biomarcadores/urina , China/etnologia , Complicações do Diabetes/sangue , Complicações do Diabetes/etnologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etnologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
15.
J Hypertens ; 26(11): 2198-206, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18854761

RESUMO

BACKGROUND: Elevated urinary albumin excretion (UAE) is more frequent in patients with the metabolic syndrome or insulin resistance. Whether UAE predicts the development of diabetes mellitus, independently of the presence or the development of the metabolic syndrome, is unclear, in particular, in women. OBJECTIVE: We prospectively assessed the association between baseline UAE and subsequent diabetes mellitus in participants selected from the general population. PARTICIPANTS AND METHODS: Four thousand and seventy-four nondiabetic patients (aged 30-64 years) included in the Data from an Epidemiological Study on the Insulin Resistance syndrome Study had a baseline UAE. Among them, 3851 patients had complete data regarding diabetes mellitus. RESULTS: Diabetes mellitus occurred in 171 out of 3851 patients during the 9-year follow-up (132/2056 men and 39/1795 women). UAE was associated with diabetes mellitus in a dose-dependent manner in men [as compared to men with UAE<9 mg/l, hazard ratios were 1.81 (P=0.0160), 1.83 (P=0.0134), 2.31 (P=0.0008) and 4.43 (P=0.0005) for men with UAE: 9-12 mg/l, 12-19 mg/l, 20-200 mg/l and >200 mg/l, respectively] but not in women; the association was more marked after exclusion of men with baseline impaired fasting glucose [hazard ratios were 3.28 (P=0.0007), 3.08 (P=0.0012), 3.27 (P=0.0022), 9.23 (P<0.0001), respectively]. The association remained significant after adjustments on BMI, sporting activity, diet, smoking, waist circumference, insulin and homeostasis model assessment of insulin resistance, lipids, C-reactive protein and family of history of diabetes mellitus. Adjustment on the first 3-year change in weight, glucose, insulin and homeostasis model assessment of insulin resistance did not modify the results. CONCLUSION: Elevated UAE predicts the 9-year risk of diabetes mellitus in men, independent of baseline or early development of metabolic abnormalities or insulin resistance.


Assuntos
Albuminúria/diagnóstico , Complicações do Diabetes/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Resistência à Insulina/fisiologia , Adulto , Albuminúria/complicações , Complicações do Diabetes/urina , Diabetes Mellitus Tipo 2/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores Sexuais
16.
Arq Bras Cardiol ; 90(2): 99-103, 2008 Feb.
Artigo em Inglês, Português | MEDLINE | ID: mdl-18392381

RESUMO

BACKGROUND: The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria and is related to a higher prevalence of cardiovascular disease. OBJECTIVE: 1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship between the presence of microalbuminuria and hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. METHODS: The presence of microalbuminuria in a group of hypertensive patients (73 individuals) and in a group of patients with coronary artery disease (39 individuals) was determined and compared with a control group (43 individuals). Microalbuminuria was defined as an albumin/creatinine ratio higher than 30 and lower than 300 in a spot morning urine sample. The chi-square test and the Fishers exact test were used in the statistical analysis. RESULTS: Microalbuminuria was present in 9.5% of the hypertensive individuals and in 33% of the patients with coronary artery disease, and was absent in individuals of the control group. When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group involved, a statistically significant correlation was found with age, diabetes and dyslipidemia. CONCLUSION: 1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation of the presence of microalbuminuria with age, diabetes and dyslipidemia.


Assuntos
Albuminúria/epidemiologia , Doença da Artéria Coronariana/urina , Hipertensão/urina , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Albuminúria/complicações , Índice de Massa Corporal , Creatinina/urina , Complicações do Diabetes/urina , Dislipidemias/complicações , Dislipidemias/urina , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/urina , Fumar/urina , Adulto Jovem
17.
J Hypertens ; 26(5): 871-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18398328

RESUMO

OBJECTIVE: Few studies have examined microalbuminuria (MAU) in non-western populations. We assessed the prevalence of MAU in the general population of a middle-income country in the African region and relationships between MAU and selected cardiovascular risk factors. METHODS: An examination survey was conducted in a sample representative of the entire population aged 25-64 years in the Seychelles. MAU adjusted for urine creatinine concentration was measured on the second morning urine using a semiquantitative point-of-care analyzer. RESULTS: A total of 1255 persons attended the survey (participation rate of 80.2%). The age-adjusted prevalence of MAU was 11.4%. At age 25-64 years, the prevalence of MAU was 5% in persons without diabetes and hypertension, 20% in persons with either condition and 41% in persons with both conditions. The overall prevalence of stages 3-4 chronic kidney disease was low at 3.2%. In multivariate analysis, MAU was associated with age [odds ratio (OR) 1.24 for a 10-year increase; 95% confidence interval (CI): 1.02-1.52], hypertension stage I (2.0; 1.1-3.8) and stage II (4.5; 2.3-8.6), obesity (1.7; 1.0-2.8) and diabetes (3.0; 1.9-4.9). These associations were virtually unchanged upon further adjustment for markers of renal function such as serum creatinine, serum cystatin C and calculated renal function. CONCLUSION: The prevalence of MAU was high in this population, and MAU was strongly associated with several cardiovascular risk factors independently of renal function markers. These findings suggest that MAU could be a useful marker of cardiovascular risk in this population and help identify persons in need of a specific cardiovascular risk management.


Assuntos
Albuminúria/epidemiologia , Complicações do Diabetes/urina , Hipertensão/urina , Adulto , Biomarcadores , Complicações do Diabetes/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Seicheles/epidemiologia
18.
Arq. bras. cardiol ; 90(2): 108-113, fev. 2008. graf, tab
Artigo em Inglês, Português | LILACS | ID: lil-479604

RESUMO

FUNDAMENTO: A taxa normal de excreção de albumina em 24 horas é de 20 mg. A taxa persistente de 30 a 300 mg/dia é chamada de microalbuminúria (MA) e está relacionada com maior prevalência de doença cardiovascular. OBJETIVO: Determinar a prevalência de microalbuminúria em um grupo de hipertensos e em um grupo de portadores de doença coronariana; e determinar a relação da presença de microalbuminúria com hipertensão arterial, diabete melitus, dislipidemia, tabagismo e obesidade. MÉTODOS:: Determinamos a presença de microalbuminúria num grupo de hipertensos (73 indivíduos) e num grupo de coronariopatas (39 indivíduos), e comparamos com um grupo-controle (43 indivíduos). Considerou-se como microalbuminúria a relação albumina/creatinina maior que 30 e menor que 300 em amostra isolada de urina matinal. Na análise estatística, foram utilizados os testes do qui-quadrado e o teste exato de Fisher. RESULTADOS: A microalbuminúria esteve presente em 9,5 por cento dos hipertensos, em 33 por cento dos coronariopatas e não esteve presente em nenhum indivíduo do grupo-controle. Ao analisar a ocorrência de microalbuminúria segundo os diversos parâmetros clínicos, independentemente do grupo a que pertenciam, verificamos correlação estatisticamente significativa com idade, diabete e dislipidemia. CONCLUSÃO: 1) A prevalência de microalbuminúria em indivíduos hipertensos é elevada, sendo ainda mais elevada em portadores de doença coronariana; 2) existe correlação da presença de microalbuminúria com idade, diabete e dislipidemia.


BACKGROUND: The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria and is related to a higher prevalence of cardiovascular disease. OBJECTIVE: 1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship between the presence of microalbuminuria and hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. METHODS: The presence of microalbuminuria in a group of hypertensive patients (73 individuals) and in a group of patients with coronary artery disease (39 individuals) was determined and compared with a control group (43 individuals). Microalbuminuria was defined as an albumin/creatinine ratio higher than 30 and lower than 300 in a spot morning urine sample. The chi-square test and the Fisher’s exact test were used in the statistical analysis. RESULTS: Microalbuminuria was present in 9.5 percent of the hypertensive individuals and in 33 percent of the patients with coronary artery disease, and was absent in individuals of the control group. When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group involved, a statistically significant correlation was found with age, diabetes and dyslipidemia. CONCLUSION: 1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation of the presence of microalbuminuria with age, diabetes and dyslipidemia.


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Albuminúria/epidemiologia , Doença da Artéria Coronariana/urina , Hipertensão/urina , Fatores Etários , Albuminúria/complicações , Índice de Massa Corporal , Creatinina/urina , Complicações do Diabetes/urina , Dislipidemias/complicações , Dislipidemias/urina , Métodos Epidemiológicos , Obesidade/urina , Fumar/urina , Adulto Jovem
19.
Med Mal Infect ; 36(4): 219-22, 2006 Apr.
Artigo em Francês | MEDLINE | ID: mdl-16580164

RESUMO

OBJECTIVES AND METHOD: The discordance between test by urine dipstick (nitrites and leucocyte-esterase) and analysis in laboratory, with urinary culture on the same sample was studied in diabetic patients, from October 2000 to May 2002, to eventually stop systematic laboratory test. The dipstick result (Clinitek 20 Bayer) was classified as "possibility of bacteriuria" if one of the two tests was positive. Bacteriuria was considered significant if the laboratory test result gave, at least 10(5) bacteria per mL, (one strain), and at least 10(4) leucocytes. The out point was the dipstick negative predictive value (NPV). RESULTS: The study included 683 patients. The dipstick result was "possibility of bacteriuria" in 153 cases (22.4%). Thirty-nine bacteriuria (5.7%) were reported, including 2 dipstick false negatives. The NPV was 99.6% [IC 95% : 99.1-100]. CONCLUSION: The systematic laboratory tests were stopped.


Assuntos
Bacteriúria/diagnóstico , Complicações do Diabetes/diagnóstico , Testes Diagnósticos de Rotina , Procedimentos Desnecessários , Urina/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriúria/epidemiologia , Bacteriúria/etiologia , Bacteriúria/urina , Criança , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/urina , Testes Diagnósticos de Rotina/estatística & dados numéricos , Suscetibilidade a Doenças , Reações Falso-Negativas , Feminino , França/epidemiologia , Glicosúria/epidemiologia , Hematúria/epidemiologia , Humanos , Corpos Cetônicos/urina , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/epidemiologia , Fitas Reagentes , Procedimentos Desnecessários/estatística & dados numéricos , Urina/citologia
20.
J Diabetes Complications ; 20(3): 188-95, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16632240

RESUMO

OBJECTIVE: There are no large studies in Type 1 diabetic patients that have examined the relation between soluble adhesion molecules and micro- and macrovascular outcomes, although the risks of such complications are high. Therefore, the main objective is to examine the relationship between soluble (s) vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin and retinopathy, albuminuria, and cardiovascular disease (CVD) in Type 1 diabetic patients. METHODS: Cross-sectional data on 540 Type 1 diabetic patients, with a mean age of 40 years and diabetes duration of 22 years, from the EURODIAB Prospective Complications Study (PCS) were analysed. Retinopathy was assessed by centrally graded retinal photographs. Albumin excretion rate (AER) was used to define micro- and macroalbuminuria. CVD was defined as having physician diagnosed myocardial infarction (MI), stroke, coronary artery bypass graft (CABG) or angina, or Minnesota coded ischaemic electrocardiograms (ECGs). RESULTS: Unadjusted, there was a positive relationship between sVCAM-1 and sE-selectin with nonproliferative and proliferative retinopathy, micro- and macroalbuminuria, and CVD. After adjustment for age, sex, duration of diabetes, systolic blood pressure (BP), LDL-cholesterol, fasting triglycerides (TGs), smoking, body mass index (BMI), and glycated haemoglobin, as well as other complications, the strongest significant associations were shown between sVCAM-1 and macroalbuminuria, with an odds ratio of 1.83 (1.33-2.53) for every 100 ng/ml increase in sVCAM-1. CONCLUSIONS: In this large sample of Type 1 diabetic patients, it was shown that sVCAM-1 and sE-selectin have positive associations with retinopathy, albuminuria, and CVD. This suggests that adhesion molecules are important in the pathogenesis of vascular complications in Type 1 diabetes.


Assuntos
Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 1/sangue , Selectina E/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto , Albuminúria/urina , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/urina , Estudos Transversais , Complicações do Diabetes/urina , Retinopatia Diabética/sangue , Retinopatia Diabética/urina , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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