Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus / Zinco-alfa2-glicoproteina (ZAG) como biomarcador precoce de nefropatia diabética em pacientes com diabetes mellitus tipo 2

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.

Macrophage migration inhibitory factor antagonist (p425) ameliorates kidney histopathological and functional changes in diabetic rats / Antagonista (p425) do fator de inibição da migração de macrófagos (MIF) melhora as alterações histopatológicas e funcionais renais em ratos diabéticos

Abstract Introduction: It is hypothesized that increased macrophage migration inhibitory factor (MIF) expression may contribute to diabetic nephropathy (DN) pathogenesis. The aim of the present study was to investigate the renal effects of MIF inhibition in a diabetic experimental model. Methods: Eighteen male Wistar rats (230 ± 20 g) were divided into three groups: 1) control, 2) diabetic (STZ, 50 mg/kg, dissolved in saline, ip), 3) diabetic + MIF antagonist (p425, 1 mg/kg per day, ip, on the 21th day, for 21 consecutive days). The treatment started since we founwd a significant increase in urine albumin excretion (UAE) rate in the diabetic rats in comparison with the control rats. The rats were kept individually in metabolic cages (8 AM-2 PM) and urine samples were collected in the 21 and 42th day. At the end, blood and tissue samples were collected for biochemical (BS, UPE, urine GAG, BUN, Cr, Na, and K) and histological analyses. Results: The results of this study showed that MIF antagonist (p425) significantly decreased urine protein and GAG excretion, urine protein/creatinine ratio, and serum BUN and Cr in the streptozotocin-induced DN in the rats. Pathological changes were significantly alleviated in the MIF antagonist (p425)-administered DN rats. Conclusion: Collectively, these data suggested that MIF antagonist (p425) was able to protect against functional and histopathological injury in the DN.

Resumo Introdução: Supõe-se que elevações da expressão do fator de inibição da migração de macrófagos (MIF) possam contribuir para a patogênese da nefropatia diabética (ND). O objetivo do presente estudo foi investigar os efeitos renais da inibição do MIF em um modelo experimental diabético. Métodos: Dezoito ratos Wistar machos (230 ± 20g) foram divididos em três grupos: 1) controle, 2) diabético (STZ 50 mg/kg dissolvida em soro fisiológico, IP), 3) diabético + antagonista do MIF (p425 1 mg/kg por dia IP no 21o dia por 21 dias consecutivos). O tratamento começou após a identificação de aumento significativo na albuminúria nos ratos diabéticos em relação aos controles. Os ratos foram mantidos individualmente em gaiolas metabólicas (8h-14h) e amostras de urina foram colhidas no 21o e no 42o dia. Ao final do estudo, amostras de sangue e tecido foram colhidas para análises bioquímicas (BS, excreção urinária de proteína, excreção urinária de GAGs, BUN, Cr, Na e K) e histológicas. Resultados: O presente estudo demonstrou que o antagonista do MIF (p425) diminuiu significativamente proteinúria, excreção urinária de GAGs , relação proteína/creatinina na urina, BUN e Cr no grupo com ND induzida por estreptozotocina. As alterações patológicas foram significativamente abrandadas nos ratos com ND que receberam antagonista do MIF (p425). Conclusão: Coletivamente, os dados sugerem que o antagonista do MIF (p425) teve efeito protetor contra lesões funcionais e histopatológicas da ND.

Is Uric Acid elevation a random finding or a causative agent of diabetic nephropathy?

SUMMARY 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.

RESUMO OBJETIVO O objetivo deste estudo foi analisar a relação entre o ácido úrico sérico e a microalbuminúria como marcador de lesão renal no diabetes mellitus tipo 2. MÉTODOS Um total de 100 pacientes com diabetes mellitus tipo 2 foram inscritos no estudo. Os grupos de estudo foram divididos em dois, de acordo com a relação microalbumina/creatinina na urina: nefropatia diabética e grupo não nefropático. UA e microalbuminúria foram comparados entre os grupos de estudo. RESULTADOS Os níveis séricos de AU de pacientes com nefropatia diabética foram significativamente maiores do que o grupo sem nefropatia (AU em pacientes com grupos de nefropatia diabética: 6,3 (1,82) mg/dl, AU em pacientes com grupos não nefropáticos: 4,85 (1,92) mg/dl ) (p<0,001). Houve correlação entre microalbuminúria e AU (r=0,238). Essa correlação foi estatisticamente significativa (p=0,017). CONCLUSÃO Os níveis de AU podem ser um importante preditor de nefropatia em pacientes diabéticos.

Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes)

ABSTRACT Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8-25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2-12.9), 8.4 (2.5-25.4), 9.1 (2.6-31.4) and 3.5 (1.4-8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies.

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients / Ácido úrico sérico e sua associação com hipertensão, nefropatia precoce e doença renal crônica em pacientes diabéticos tipo 2

Abstract Introduction: Early detection diabetic nephropathy (DN) is important. Whether serum uric acid (SUA) has a role in the development of DN is not known. Objective: To study the relationship between SUA and hypertension, early nephropathy and progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Methods: The total number of the study was 986 participants, according to presence and duration of diabetes were classified into three groups. Group I; including 250 healthy participants. Group II; including 352 with onset of diabetes < 5 years. Group III; including 384, with the onset of diabetes > 5 years. All participants were submitted to complete clinical examination, anthropometric measurements, laboratory investigations, including glycosylated hemoglobin (HbA1C), as well triglycerides to high-density lipoprotein ratios (TG/HDL-C), SUA, urinary albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Results: SUA, BP, HbA1c, TG/HDL-C ratio, and ACR levels were significantly higher in group III than group I, II and in II than I. eGFR significantly lower in group III than group I, II and in II than I (p < 0.001). Age, BMI, BP, HbA1c, TG/HDL-C, ACR, were positively correlated with SUA, while GFR negatively correlated. SUA at level of > 6.1 mg/dl, > 6.2 mg/dl and > 6.5 mg/dl had a greater sensitivity and specificity for identifying hypertension, early nephropathy and decline eGFR respectively. Conclusion: Even high normal SUA level, was associated with the risk of hypertension, early nephropathy and decline of eGFR. Moreover SUA level may identify the onset of hypertension, early nephropathy and progression of CKD in T2DM.

Resumo Introdução: A detecção precoce da nefropatia diabética (ND) é importante. O ácido úrico sérico (AUS) tem um papel ainda desconhecido no desenvolvimento de ND. Objetivo: Estudar a relação entre AUS e hipertensão, nefropatia precoce e progressão da doença renal crônica (DRC) no diabetes mellitus tipo 2 (DM2). Métodos: O estudo contou com 986 participantes, de acordo com a presença e a duração do diabetes, os pacientes foram classificados em três grupos. O Grupo I incluiu 250 participantes saudáveis. O Grupo II incluiu 352 pacientes com início de diabetes < 5 anos. O Grupo III incluiu 384 pacientes com o aparecimento de diabetes > 5 anos. Todos os participantes foram submetidos a exame clínico completo, medidas antropométricas, exames laboratoriais - incluindo hemoglobina glicosilada (HbA1C), bem como a razão entre triglicérides e lipoproteína de alta densidade (TG/HDL-C), AUS, razão creatinina/albumina (RCA) urinária, e taxa estimada de filtração glomerular (eTFG). Resultados: A razão AUS, PA, HbA1c, TG/HDL-C e RCA foi significativamente maior no grupo III do que no grupo I, II e em II do que I. A eTFG foi significativamente menor no grupo III do que nos grupos I, II e no II do que no I (p < 0,001). Idade, IMC, PA, HbA1c, razão TG/HDL-C, RCA, foram positivamente correlacionados com AUS, enquanto que a TFG esteve negativamente correlacionada. O AUS a níveis > 6,1 mg/dl, > 6,2 mg/dl e > 6,5 mg/dl apresentou maior sensibilidade e especificidade para identificar hipertensão, nefropatia precoce e declínio da eTFG, respectivamente. Conclusão: Mesmo elevados níveis de AUS, foi associado ao risco de hipertensão, nefropatia precoce e declínio da eTFG. Além disso, o nível de AUS pode identificar o início da hipertensão, nefropatia precoce e progressão da DRC em DM2.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Comparación entre las fórmulas Cockcroft-Gault y MDRD para estimar velocidad de filtración glomerular en diabéticos / Comparison between Cockcroft-Gault and MDRD formulas to estimated glomerular filtration rate in diabetic people

INTRODUCCIÓN: La nefropatía diabética es una complicación relevante de la Diabetes Mellitus. Por esto, la American Diabetes Association (ADA) recomienda la determinación de la velocidad de filtración glomerular (VFG) como screening de nefropatía. Existe una fórmula, la MDRD (Modification of Diet in Renal Disease), que permite hacer una estimación bastante exacta dela VFG. La utilización de ésta ha sido comparada permanentemente con la Cockcroft-Gault. OBJETIVO: comparar ambas fórmulas para la VFG en la realidad local. MATERIAL Y MÉTODO: se realizó un estudio retrospectivo sobre 243 pacientes, seleccionados al azar, de un total de 1.057 pacientes diabéticos tipo 2 registrados en el Plan de Salud Cardiovascular en el CESFAM San Rafael de la comuna La Pintana que contaban con medición seriada de Creatinina plasmática en sus controles periódicos. Se consideraron los valores de creatinina plasmática más recientes tomados en el período Enero 2010-Octubre 2011 y obtuvimos la VFG aplicando ambas fórmulas. RESULTADOS: del total de pacientes seleccionados, 158 fueron mujeres (65 por ciento) y 85 hombres (35 por ciento), con una media de edad de 53 años (DE 8,08). La VFG media estimada con MDRD fue de 89 ml/min/1,73 m2 (DE 21) y con la Cockcroft-Gault fue de 108 ml/min (DE 32), p<0,001. Realizamos un estudio de correlación entre ambas fórmulas. DISCUSIÓN: ambas mostraron correlación aceptable para estimar la VFG, aunque en pacientes obesos las estimaciones de VFG fueron más elevadas con Cockcroft-Gault que con MDRD. Por otro lado, en pacientes añosos la tendencia fue a que la fórmula MDRD diera estimaciones más altas.

INTRODUCTION: Diabetic Nephropathy is a significant complication of Diabetes Mellitus. That’s why, the American Diabetes Association (ADA) recommended for screening the determination of the glomerular filtration rate (GFR). MDRD (Modification of Diet in Renal Disease), is a formula which allows a very exactly estimation of GFR. Permanently, it had always been compared with Cockcroft-Gault formula. OBJECTIVE: Compare both formulas in the local reality. MATERIAL AND METHOD: It was done a retrospective studio over 243 patients, randomly selected, of a total of 1,057 type 2 diabetes patients registered in Cardiovascular program of San Rafael CESFAM that had serial measurement of plasmatic creatinine in their periodic controls. It was considered the most recent values of plasmatic creatinine taken between January 2010 – October 2011. RESULTS: Of the patients selected, 158 women (65 percent) and 85 men (35 percent), with average age of 53 years (SD 8,08), the GFR estimated with MDRD was of 89 ml/min/1.73 m2 (SD 21) and 108 ml/min (SD 32) for Cockcroft-Gault formula, p<0.001. We realized a correlation studio between both formulas. DISCUSSION: Both formulas demonstrated an acceptable correlation to estimated GFR, although obese patients had higher estimations with Cockcroft-Gault formula, on the other side, elderly patients had elevated results with MDRD.

Relationship between serum nitric oxide and sialic acid in coexisted diabetes, hypertension and nephropathy

This study was designed to study the relationship between serum nitric oxide and sialic acid in patients of diabetic nephropathy. Total 210 diabetic patients including 115 males and 95 females, suffering from diabetes and nephropathy [DN] were selected followed by informed consent and approval from institutional ethical committee. Equal number of age and sex matched normal healthy subjects were selected without any known history of hyperglycemia, hypertension and renal insufficiency as controls. Fasting blood samples from patients and controls were collected and analyzed for serum nitric oxide, sialic acid, fasting blood glucose [FBG], serum urea, creatinine, HbA1c and golmerular filtration rate [GFR]. The raised levels [p<0.05] of systolic and diastolic blood pressures, BMI, FBG, HbA1c, serum urea, creatinine and sialic acid were noted in DN patients as compared to controls. Significantly lower levels of GFR and serum nitric oxide [p<0.05] were observed in DN patients as compared to controls. Strong negative correlation was found between serum sialic acid and nitric oxide levels in patients diabetic nephropathy [p<0.05]. The relationship between the levels of serum nitric oxide and sialic acid may be considered as a strong biochemical indicator for micro and macro vascular complications of diabetes such as hypertension and nephropathy. These parameters should be taken into account during screening procedures regarding identifications of the diabetic patients to get them rid of progressive renal impairment to ESRD

Clinical features of patients with type 2 diabetes mellitus and hepatitis C infection

The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9 percent) outpatients and in 34 of 186 (18.7 percent) dialysis patients. Among HCV+ patients, 32 were men (43.8 percent). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 µKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 µKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 µKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 µM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7 percent; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.

Acido úrico, aterosclerosis y calcificaciones vasculares en enfermedad renal crónica / Uric acid, atherosclerosis and vascular calcifications in chronic kidney disease

Estudios clínicos y epidemiológicos han demostrado que la enfermedad cardiovascular está relacionada con un aumento en la tasa de mortalidad en los pacientes con enfermedad renal crónica (ERC). Las complicaciones vasculares son principalmente secundarias a calcificaciones y ateroesclerosis. En los últimos años se ha renovado el interés por la asociación entre niveles de ácido úrico y riesgo cardiovascular. El objetivo de esta investigación fue relacionar la presencia de calcificaciones vasculares (CV) y aterosclerosis, evaluadas mediante ecografía carotídea, con niveles de ácido úrico en pacientes con ERC estadio 5 en diálisis. Se observaron CV en 56% de los pacientes; 46% tuvo criterios ecográficos para aterosclerosis con un promedio general de 0,89 mm (DE: ± 0,28), siendo mayor en los pacientes con hipertensión arterial y diabetes mellitus; este grupo también mostró mayor predisposición para CV (p= 0,01). Los niveles de urea (141,3 mg/dL) (p= 0,01) y ácido úrico (6,9 mg/dL) (p= 0,04) mostraron asociación estadísticamente significativa con la presencia de CV. Los eventos cardiovasculares adversos predominaron en los pacientes con aterosclerosis y CV (p= 0,01). Esta investigación demostró que un incremento en los niveles de ácido úrico por encima de 6 mg/L está relacionado con mayor riesgo de presentar calcificaciones y eventos cardiovasculares adversos en pacientes con ERC.

Epidemiological and clinical studies have shown that cardiovascular disease is associated with an increase in mortality in patients with chronic kidney disease (CKD). Vascular complications are mainly secondary to calcification and atherosclerosis. Interest in the association between uric acid levels and cardiovascular risk has been renewed in recent years. The objective of this research was to determine the relation between vascular calcification (VC) and atherosclerosis, through carotid ultrasound, with uric acid levels in patients with CKD in dialysis. VCs were observed in 56% of patients, 46% had ultrasound criteria for atherosclerosis with an overall average of 0.89 mm (SD ± 0.28), being higher in patients with hypertension and diabetes; this group also showed increased susceptibility to VC (p= 0.01). The levels of urea (141.3 mg/dL) (p= 0.01) and uric acid (6.9 mg/dL) (p= 0.04) showed significant association with the presence of VC. Adverse cardiovascular events were observed mainly in patients with atherosclerosis and VC (p= 0.01). This investigation showed that an increase in uric acid levels above 6 mg/dL is associated with an increased risk of calcification and cardiovascular adverse events in CKD patients in dialysis.

Low Hemoglobin Concentration Is Associated with Several Diabetic Profiles

No abstract available.

Associations between Hemoglobin Concentrations and the Clinical Characteristics of Patients with Type 2 Diabetes

BACKGROUND/AIMS: Many studies have demonstrated an association between hemoglobin levels and cardiovascular disease in diabetic patients. The aim of this study was to determine whether there is an association between hemoglobin concentrations and various clinical parameters, including metabolic factors, plasma C-peptide response after a meal tolerance test, and microvascular complications, in Korean patients with type 2 diabetes. METHODS: In total, 337 male patients with type 2 diabetes were recruited. All subjects were subjected to a meal tolerance test and underwent assessment of hemoglobin levels, fasting and postprandial beta-cell responsiveness, and microvascular complications. RESULTS: Patients with lower hemoglobin concentrations had a longer duration of diabetes, a lower body mass index, and lower concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. They also had lower levels of postprandial C-peptide, Delta C-peptide, and postprandial beta-cell responsiveness. They had a higher prevalence of retinopathy and nephropathy. In multivariate analyses, there was a significant association between nephropathy and hemoglobin concentration. Also, hemoglobin concentrations were independently associated with Delta C-peptide levels and postprandial beta-cell responsiveness. CONCLUSIONS: Hemoglobin concentrations are associated with postprandial C-peptide responses and diabetic nephropathy in patients with type 2 diabetes.

Cystatin C as an Early Biomarker of Nephropathy in Patients with Type 2 Diabetes

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.

Glycemic and lipidic profile in diabetic patients undergoing dialysis / Controle glicêmico e lipídico no paciente diabético em diálise

OBJECTIVE: The aim of this study is to assess the clinical care pattern and to compare the lipid and glycemic profile in a group of diabetic patients undergoing both hemodialysis (HD) and peritoneal dialysis (PD) and to correlate these data using biomarkers of cardiovascular risk. SUBJECTS AND METHODS: The first phase consisted in performing a survey on demographic data, questions about the medical team and glycemic control. In the second phase, patients were assessed through laboratorial data on their glycemic and lipid profile at a single center for HD and PD. RESULTS: 91 patients was the total population; 70 patients (77 percent) answered the survey; 66 patients (94 percent) considered the nephrologist the physician responsible for caring for their glycemic control. Second phase: 59 patients were assessed, 29 undergoing HD and 30 undergoing PD. Fifty-seven percent of the patients had HbA1c above 7 percent; the level of glycemic markers in patients undergoing peritoneal dialysis was significantly higher than in patients undergoing hemodialysis: HbA1c (9.37 ± 0.5) vs. (7.37 ± 0.49) p < 0.01; fasting glycemia (170 ± 15) vs. (126 ± 15) mg/dL p < 0.05. We found a positive correlation between HbA1c and hyperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSIONS: The data reveal that glycemic control in diabetic patients undergoing renal replacement therapy (RRT) is neglected. Peritoneal dialysis is related to the worst level of glycemic markers, possibly due to the glucose content in the dialysis solution, and higher levels from HbA1c have a positive correlation with hyperfibrinogenesis in this population.

OBJETIVO: Avaliar as características dos cuidados clínicos dos pacientes em diálise, comparar o controle glicêmico e lipídico entre os pacientes diabéticos em hemodiálise (HD) e em diálise peritoneal (DP) e correlacionar os dados laboratoriais com biomarcadores de risco cardiovascular. SUJEITOS E MÉTODOS: A primeira etapa consistiu de um questionário abordando variáveis demográficas, questões sobre a equipe multidisciplinar, incluindo a equipe médica e sobre o controle glicêmico. Na segunda, os pacientes foram avaliados com exames laboratoriais para controle glicêmico e perfil lipídico numa unidade de HD e DP. RESULTADOS: Dos 91 pacientes avaliados, setenta (77 por cento) responderam ao questionário. Destes, 66 (94 por cento) consideraram o nefrologista o médico responsável pelo cuidado do seu controle glicêmico. Na segunda etapa, foram avaliados 59 pacientes: 29 em HD e 30 em DP. Cinquenta e sete por cento dos pacientes diabéticos em diálise apresentaram HbA1c acima de 7 por cento, sendo que aqueles em diálise peritoneal apresentam níveis de marcadores glicêmicos significativamente piores do que os pacientes diabéticos em HD, HbA1c: (9,37 ± 0,5) vs. (7,37 ± 0,49) p < 0.01; glicemia de jejum: (170 ± 15) vs. (126 ± 15) mg/dL, p < 0.05. Encontramos uma correlação positiva entre HbA1c e hiperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSÕES: Nossos dados permitem inferir que o controle glicêmico da população diabética em terapia renal de substituição (TRS) é negligenciado. A diálise peritoneal está relacionada com piora nos níveis de marcadores glicêmicos, possivelmente em decorrência do conteúdo de glicose das soluções de diálise, e os níveis elevados de HbA1c estão associados com hiperfibrinogenemia nesta população.

Effect of GSTM1 and GSTT1 double deletions in the development of oxidative stress in diabetic nephropathy patients.

Association of diabetic nephropathy (DN) with the deletion of GSTT1 and GSTM1 genes is well reported. Oxidative stress (OS) has also been associated with the development of DN. The present study was conducted to find out, whether these deletions had any contributory role in the development of OS in patients with DN. Pre-dialysis venous blood samples were obtained from 60 patients with diabetic end-stage renal disease (stages 4 and 5). Reduced-glutathione (GSH), glutathione S-transferase (GST) activity and malondialdehyde (MDA) levels were measured for the assessment of OS. Genetic polymorphism analysis of DN patients revealed the following distribution pattern: GSTM1 null 46.7%; GSTT1 null 55%; both null 30% and both positive 28.3%. Patients with both null genotypes were found to have significantly increased levels of MDA and low GST activity as compared to other genotypic groups. Lower GSH levels were observed in all the genotypic groups as compared to both positives. Double deletions involving GSTT1 and GSTM1 may result in decreased GST levels, leading to increased OS as reflected by increased MDA levels. As GST is a multi-functional enzyme involved in xenobiotic metabolism, this double null genotype population has a greater risk of development of DN. Further studies using increased sample size to find out the allelic distribution and their role in the development of DN are in progress.

Diabetes y hemodiálisis. Caracterización de una cohorte y seguimiento a cuatro años / Assessment and follow up of diabetic patients in hemodialysis

Background: Despite a better management of the variables that influence the development of diabetic nephropathy there is a progressive increase in the prevalence of terminal renal failure among diabetics, whose cause is not clear. Aim: To study in a group of patients in hemodialysis, the quality of diabetes control previous to the entry to dialysis, their physical condition and their evolution. Material and methods: Diabetic patients with at least three months of hemodialysis answered a questionnaire about diabetes control quality previous to dialysis and had physical and laboratory assessment. They were followed for at least four years thereafter. Results: Fifty seven patients aged 62±11 years were studied. Eighty four percent had some degree of disability. Eighty seven percent had high blood pressure and 73 percent had to enter dialysis as an emergency. Mean glycosilated hemoglobin was 7.7 percent and 58 percent had a dialysis dose with a Kt/Vofless than 1.2. Fifty eight percent died during follow up. No relationship between mortality and age, blood pressure, glycosilated hemoglobin of Kt/V, was observed. Conclusions: There is an inadequate management of blood glucose and blood pressure of diabetic patients before entry to dialysis. They are referred ¡ate to the nephrologist, the dialysis dose is insufficient and they have a high mortality.

Abnormal kinetics of erythrocyte sodium lithium countertransport in patients with diabetic nephropathy in Thailand.

BACKGROUND: In essential hypertension and diabetic nephropathy, sodium-lithium counter transport (Na/Li CT) is an inherited marker for metabolic influences of cardiovascular risk. The kinetics of Na/Li CT are modified by two types of thiol group in the membrane. In choline medium, the type 1 thiol reacts with N-ethtyl maleimide (NEM) to cause a decrease in Km and increase Vmax/Km ratio. However in the presence of external Na or Li both the type 1 or type 2 thiols react so that both Km and Vmax are reduced. Low Km of Na/Li CT has been previously reported to be a major abnormality in diabetic nephropathy (DN) and can be used to identify diabetic patients who are at high risk for DN. A recent study showed that the type 1 thiol protein controlling the Km of Na/Li CT was a 33-kD protein and the gene for this protein is going to be cloned. OBJECTIVE: The authors sought to identify Na/Li CT kinetic abnormalities in Type 2 diabetes in Thai patients. MATERIAL AND METHOD: Erythrocyte Na/Li CT kinetics and their modulation by thiol proteins were measured in erythrocytes from 22 patients with Type 2 diabetes and 42 normal control subjects. RESULTS: The kinetics of Na/Li CT in untreated erythrocytes were similar Thiol protein alkylation with NEM generally caused both Vmax and Km to fall, but caused Km to rise in erythrocytes of diabetic patients, whose native Km was low. Thus, abnormalities in the regulation of Na/Li CT by key thiol proteins were found in about one-third of subjects with Type 2 diabetes in Thailand. CONCLUSION: Membrane abnormalities may indicate a common pathway of pathological mechanism found in essential hypertension and diabetic nephropathy and may be used as a phenotype for further genetic studies of this transporter.

Plasma Levels of Tissue Factor Antigen in Patients with Non-Insulin-Dependent Diabetes Mellitus

Patients with diabetes mellitus (DM) are associated with an increased risk of thrombosis, and are susceptible to a series of complications including nephropathy. It has also been known that plasma tissue factor (TF) antigen levels increase significantly in certain disease states. To investigate the clinical significance of an association with the various complications in patients with type 2 non-insulin-dependent DM (NIDDM), we measured the plasma levels of TF antigen in 63 patients (35 males and 28 females, mean age 60.8 yrs) with NIDDM and in 22 normal subjects (14 males and 8 females, mean age 56.0 yrs). The mean concentrations of TF were higher for patients with NIDDM (253.7 +/- 144.9 pg/ml) than in normal subjects (187.3 +/- 108.7 pg/ml with marginal statistical significance (p= 0.0530). The TF levels were higher for patients with a nephropathy than for patients without a nephropathy (p=0.0402). There was a significant positive correlation between levels of TF and BUN (r=0.84, p < 0.0001) or creatinine (r=0.93, p < 0.0001). However, TF levels were found to be similar for both groups with and without thrombosis, neuropathy, retinopathy, or infection. These results suggest that plasma TF antigen levels may be associated with nephropathy and they may reflect a renal dysfunction in NIDDM.

Serum cystatin C as a marker of renal affection in diabetic renal disease

This study aimed to assess clinical usefulness of measurement of serum cystatin C as a marker of renal affection in different stages of diabetic renal disease. The study included 40 patients with either types of diabetes mellitus [DM] at different stages of diabetic nephropathy [DN] as well as 20 healthy subjects matched for age and sex as controls. All the participants were investigated for renal function tests [S creatinine, urea, creatinine clearance], urine strip testing for microalbuminuria [Micral test], quantitative 24 hour urinary protein assessment, renal isotope scan by TC99 DTPA to assess GFR and finally an assessment of S cystatin C level by particle enhanced turbidimetric immunoassay [PETIA] technique

Plasma type IV collagen and fibronectin concentrations in diabetic patients with microangiopathy

In diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. We evaluated whether the plasma levels of type IV collagen and fibronectin, which are important factors of basement membrane, are related with the presence of diabetic microangiopathy. Plasma type IV collagen and fibronectin levels were measured in 40 healthy controls (Mean +/- SD, age; 50.3 +/- 5.5 yr) and 94 diabetic patients (age; 52.4 +/- 13.5 yr) with and without microvascular complications. The mean plasma levels of type IV collagen (5.3 +/- 2.9 ng/ml) and fibronectin (474.4 +/- 119.4 ug/ml) in diabetic patients were significantly higher (p < 0.01) than in healthy controls (3.7 +/- 1.3 ng/ml and 319 +/- 50.9 ug/ml). The mean plasma level of type IV collagen in diabetic patients with complications (6.6 +/- 3.7 ng/ml) was significantly higher (p < 0.01) than in those without complications (4.3 +/- 1.7 ng/ml) and became higher in more complicated patients. Furthermore, the severity of retinopathy and several indicators of nephropathy such as serum BUN, creatinine and proteinuria were closely associated with plasma type IV collagen level and a significant correlation was found between plasma type IV collagen and creatinine clearance (r = -0.31, p < 0.001). There was no significant difference in plasma fibronectin concentrations, however, between the diabetic patients with complications and those without complications.(ABSTRACT TRUNCATED AT 250 WORDS)