RESUMO
BACKGROUND: The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers. METHODS: A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron. RESULTS: The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile. CONCLUSIONS: Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.
Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/fisiopatologia , Inflamação/diagnóstico , Proteínas de Ligação ao Ferro/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Incidência , Inflamação/epidemiologia , Inflamação/genética , Inflamação/metabolismo , Proteínas de Ligação ao Ferro/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , FrataxinaRESUMO
BACKGROUND: Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. RESULTS: Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations ≥ 6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). CONCLUSIONS: High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Ácido Úrico/sangue , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/urina , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Interleucinas/urina , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/urinaRESUMO
BACKGROUND: Gamma-glutamyltransferase (GGT) is present mainly in proximal renal tubule, and urinary GGT is an indicator of tubular damage since it may show renal changes before they are identified by using conventional measurements. Therefore, it is of interest to establish the reference limits of urinary GGT for a healthy population, as well as to investigate the stability of GGT in urine samples stored at 4⯰C and -20⯰C. METHODS: GGT was assessed in urine samples from 127 healthy patients by use of a reference method based on the 5-Amino-2-Nitrobenzoate formation. Stability of GGT was evaluated in 10 urine samples stored at temperatures of 4⯰C and -20⯰C for a period up to 4â¯weeks. RESULTS: Urinary GGT values for healthy volunteers were 14â¯U/g creatinine for the lower reference limit and 79â¯U/g creatinine for the upper reference limit. Urinary GGT values were approximately 56% lower in samples stored at -20⯰C than fresh samples, while samples stored at 4⯰C presented a decrease of 11% in GGT values compared to fresh samples. CONCLUSIONS: Reference limits for urinary GGT in healthy subjects were 14 to 79â¯U/g creatinine, and it is recommended to measure urinary GGT in fresh specimens.
Assuntos
Criopreservação/métodos , gama-Glutamiltransferase/normas , Criopreservação/normas , Armazenamento de Medicamentos/métodos , Armazenamento de Medicamentos/normas , Estabilidade Enzimática , Voluntários Saudáveis , Humanos , Valores de Referência , Temperatura , gama-Glutamiltransferase/metabolismo , gama-Glutamiltransferase/urinaRESUMO
Urinary markers of nucleic acid oxidation may be useful biomarkers in diabetes. It has been demonstrated that T2DM patients have an increased level of oxidative DNA damage; however, it is unclear whether increased DNA damage may be related to a greater degree of inflammation and insulin resistance. Thus, the aim of this present study was to investigate the relation of the impact of oxidative DNA damage, assessed by urinary 8-OHdG, on the levels of inflammatory cytokines, as well as insulin resistance. In addition, we also investigated the diagnostic ability of urinary 8-OHdG in the identification of microvascular complications in T2DM.A case-control study, enrolling 22 healthy controls and 54 subjects with T2DM, was performed to evaluate the relation between oxidative DNA damage and interleukin-6 (IL-6), IL-1,tumor necrosis factor-alpha (TNF-α), IL-10, and Homeostasis Model Assessment (HOMA-IR) index. T2DM patients presented higher urinary 8-OHdG, IL-6, IL-1, TNF-α levels and HOMA-IR, and lower IL-10 levels than control subjects. Moreover, urinary 8-OHdG levels were significantly higher in the group T2DM with microvascular complications when compared to the without complications. The areas under the curve for urinary 8-OHdG and urinary albumin were, respectively, 0.836 (P<0.001) and 0.786 (P=0.002). Thus, urinary 8-OHdG has a slightly higher ability to discriminate microvascular complications in T2DM compared with urinary albumin. It was also demonstrated that T2DM patients with higher median of urinary 8-OHdG had significantly elevated levels of IL-6, TNF-α and HOMA-IR, and decreased IL-10 levels. Our findings showed that T2DM patients with higher urinary 8-OHdG levels showed a greater inflammatory degree and higher insulin resistance. It is possible to speculate that T2DM patients present a cascade of events as increasing metabolic abnormalities such as insulin resistance and inflammatory activation, as well as increased ROS generation factors that may contribute directly to greater oxidative DNA damage.