Relationship between short and long-term glycemic variability and oxidative stress in type 1 diabetes mellitus under daily life insulin treatment.

OBJECTIVE: The purpose of this study was to investigate the heterogeneity of the association between glycemic variability and oxidative stress markers in T1DM patients under daily life insulin treatment. METHODS: We studied, in a cross-sectional analysis, 76 T1DM patients without clinical chronic diabetes complications and 22 healthy individuals. Were evaluated the short-term glycemic variability (STGV), long-term glycemic variability (LTGV), oxidative stress markers [8-isoprostaglandin-F2α (Ur-8-iso-PGF2α), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and erythrocytes reduced/oxidized glutathione (GSH/GSSG)] and biochemical dosages (glycaemia, HbA1c, lipidogram, albuminuria). RESULTS: Plasmatic NO was positively associated with LTGV (last year average of HbA1c) (8.7 ± 1.6% or 71 ± 18 mmol) (rS: 0.278; p: 0.042). Plasmatic TBARS, erythrocytes GSH/GSSH and Ur-8-iso-PGF-2α didn't show correlation with glycemic variability. GSH/GSSG was inversely correlated with LDL-cholesterol (rS: - 0.417; p: 0.047) and triglycerides (rS: -0.521; p: 0.013). Albuminuria was positive correlated with age (rS: 0.340; p: 0.002), plasmatic NO (rS: 0.267; p 0.049) and TBARS (rS: 0.327; p: 0.015). CONCLUSION: In daily life insulin treatment, young T1DM patients have higher plasmatic NO than healthy subjects. However, the correlation between glycemic variability and oxidative stress markers is heterogeneous. Lipid profile and albuminuria are associated with different oxidative stress markers. These data collaborate to explain the controversial results in this issue.

Relationship between short and long-term glycemic variability and oxidative stress in type 1 diabetes mellitus under daily life insulin treatment

ABSTRACT Objectives: The purpose of this study was to investigate the heterogeneity of the association between glycemic variability and oxidative stress markers in T1DM patients under daily life insulin treatment. Subjects and methods: We studied, in a cross-sectional analysis, 76 T1DM patients without clinical chronic diabetes complications and 22 healthy individuals. Were evaluated the short-term glycemic variability (STGV), long-term glycemic variability (LTGV), oxidative stress markers [8-isoprostaglandin-F2α (Ur-8-iso-PGF2α), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and erythrocytes reduced/oxidized glutathione (GSH/GSSG)] and biochemical dosages (glycaemia, HbA1c, lipidogram, albuminuria). Results: Plasmatic NO was positively associated with LTGV (last year average of HbA1c) (8.7 ± 1.6% or 71 ± 18 mmol) (rS: 0.278; p: 0.042). Plasmatic TBARS, erythrocytes GSH/GSSH and Ur-8-iso-PGF-2α didn't show correlation with glycemic variability. GSH/GSSG was inversely correlated with LDL-cholesterol (rS: - 0.417; p: 0.047) and triglycerides (rS: −0.521; p: 0.013). Albuminuria was positive correlated with age (rS: 0.340; p: 0.002), plasmatic NO (rS: 0.267; p 0.049) and TBARS (rS: 0.327; p: 0.015). Conclusion: In daily life insulin treatment, young T1DM patients have higher plasmatic NO than healthy subjects. However, the correlation between glycemic variability and oxidative stress markers is heterogeneous. Lipid profile and albuminuria are associated with different oxidative stress markers. These data collaborate to explain the controversial results in this issue.

Cbfa1 expression in vascular smooth muscle cells may be elevated by increased nitric oxide/iNOS.

INTRODUCTION: Vascular calcification is a common complication of chronic kidney disease. Osteoblast differentiation factor (Cbfa1) is present in histologic sections of arteries from patients with end-stage renal disease. Vascular smooth muscle cells (VSMC) can dedifferentiate to osteoblast-like cells, possibly by up-regulation of Cbfa1. There is evidence that the production of nitric oxide (NO) may have an important role in the regulation of osteoblast metabolism. The aim of this study is to evaluate whether increased NO/iNOS expression causes an increase in cbfa1 expression in VSMC. METHODS: VSMC were obtained from renal artery of Wistar male rats, treated for 72 hours with lipopolysaccharide (LPS), ß-glycerophosphate (BGF), a donor of phosphate and aminoguanidine (AG), an inhibitor of iNOS, in the following groups: CTL (control), LPS, BGF, LPS + BGF, and LPS + AG. NO synthesis was determined by chemiluminescence. Cbfa1 and iNOS mRNA expressions were analyzed by RT-PCR, Cbfa1 protein expression by immunohistochemistry and cellular viability by acridine orange. RESULTS: Cbfa1 and iNOS mRNA expressions were higher in LPS and LPS+ BGF vs CTL (p < 0.05), and they were lower in LPS+AG vs LPS (p < 0.05). The Cbfa1 in the groups LPS and LPS+BGF also resulted in a higher value compared to CTL (p < 0.05), and in LPS+AG it was lower compared to LPS (p < 0.05). NO was higher in LPS and LPS+BGF compared to CTL group (p < 0.05) and lower in LPS + AG compared to LPS group (p < 0.05). Cellular viability showed no statistical difference among groups. CONCLUSION: This study showed that increased NO/iNOS expression causes an increase in cbfa1 expression in VSMC.

There Is No Impact of Diabetes on the Endothelial Function of Chronic Kidney Disease Patients.

BACKGROUND: Patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction, cardiovascular disease, and mortality. Several studies have separately analyzed endothelial function in these populations. However, data of patients with both CKD and DM are scarce. The aim of this study was to evaluate whether the presence of DM has any additional effect on the endothelial dysfunction of CKD patients. METHODS: We measured endothelial progenitor cells (EPCs), stromal-derived factor 1 alpha (SDF-1α), serum and urinary nitric oxide (NO), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in 37 CKD patients with DM (CKD-DM group) and in 37 without DM (CKD group). RESULTS: CKD-DM group had a higher prevalence of obesity (P < 0.01), previous myocardial infarction (P = 0.02), myocardial revascularization (P = 0.04), and a trend for more peripheral artery disease (P = 0.07). Additionally, CKD-DM group had higher EPC (P = 0.001) and PWV (P < 0.001) values. On the other hand, no difference in SDF-1α and serum or urinary NO and FMD was observed between the groups. CONCLUSIONS: Endothelial dysfunction is frequent in CKD patients, and an additive effect of diabetes cannot be implicated, suggesting the predominant role of uremia in this condition.

Nitric oxide (NO) is associated with gentamicin (GENTA) nephrotoxicity and the renal function recovery after suspension of GENTA treatment in rats.

GENTA nephrotoxicity is likely to be caused, among other factors, by an increase of vasoconstrictors or a decrease of vasodilators such as NO. Few days after discontinuing GENTA treatment, the renal function is recovered, but if risk factors like advanced age, previous renal dysfunction, simultaneous use of other nephrotoxic drugs or dehydration are present, severe and progressive renal disease occurs. The aim of this study was to evaluate the renal function in rats during GENTA treatment and after its suspension as well as its relationship with NO. Rats were treated with water (vehicle, CTL) or GENTA (100 mg/kg BW) intraperitonially during 10 days; both n=24. Twelve animals of each group were sacrificed after blood and 24 h urine were collected, and their kidneys were removed for histology. In another rats this procedure underwent after 20 or 30 days of GENTA suspension. GENTA treated group developed a marked decrease in renal function, characterized by an increased serum urea and decreased creatinine clearance; NO was increased in the serum and decreased in the urine; all P < 0.01 vs CTL. Acute tubular necrosis was confirmed in GENTA treated group. After GENTA suspension we observed a normalization of urea, creatinine clearance and serum and urinary NO; the histological lesions were also attenuated. We suggest that NO could play a role in GENTA induced nephrotoxicity and recovery. The understanding of this physiopathology could be an useful tool to prevent or blunt the nephrotoxicity progression, mainly when risk factors are present.

Suplementação proteica não aumenta a concentração plasmática de óxido nítrico em homens saudáveis / Protein supplementation does not increase nitric oxide plasmatic concentration in healthy men

Suplementos nutricionais, supostamente, capazes de potencializar a produção endógena de óxido nítrico (NO) têm experimentado crescente popularidade entre os indivíduos fisicamente ativos. Diante da carência de informações sobre o assunto, o objetivo do presente estudo foi avaliar o efeito de um suplemento comercial à base de proteínas e aminoácidos sobre a produção endógena de NO. MÉTODOS: A amostra foi constituída de 12 homens sedentários, mas sem fatores de risco para doenças cardiovasculares. O protocolo de suplementação foi conduzido conforme o arranjo experimental duplo-cego cruzado. Os participantes receberam, aleatoriamente, placebo (PLA) ou suplemento proteico (SP), em dois momentos diferentes, separados por uma semana. Com o intuito de determinar a concentração plasmática de NO, amostras de sangue foram coletadas antes (24h e imediatamente antes) e depois (30 e 60 minutos) do consumo da substância PLA ou do SP. RESULTADOS: Não foi observada alteração na concentração plasmática de NO após a ingestão do SP em comparação com o PLA (pós- suplementação 30min - PLA: 19,3 ± 4,7µmol.L- 1 vs. SP: 18,9 ± 4,4µmol.L-1 e pós-suplementação 60min - PLA: 21,3 ± 6,5µmol.L-1 vs. SP: 20,3 ± 4,9µmol.L-1). Também não foi verificada alteração da pressão arterial. CONCLUSÃO: O suplemento nutricional à base de proteínas e aminoácidos, testado no presente estudo, não potencializou a produção endógena de NO.

Nutritional supplements, theoretically able to increase endogenous nitric oxide (NO) production have experienced great popularity among physically active individuals. AIM: scientific evidence available regarding this issue is scarce. Therefore, the purpose of this study was to evaluate the effect of a dietary supplement commercialized as a nitric oxide booster. MATERIALS AND METHODS: twelve sedentary men with no risk factors for cardiovascular diseases were supplemented with placebo or protein in two different occasions. The present study was conducted in a cross double-blind design. In order to assess plasmatic NO concentration, blood samples were obtained before (24hs and immediately before) and after (30 and 60 minutes) consumption of placebo (PLA) or protein supplement (SP). RESULTS: there was no difference in plasmatic nitric oxide concentration between both trails (Post-supplementation 30 min - PLA: 19.3±4.7 µmol.L-1 vs. SP: 18.9±4.4 µmol.L-1 and Post-supplementation 60 min - PLA: 21.3±6.5 µmol.L-1 vs. SP: 20.3±4.9 µmol.L-1). In addition, no difference was detected for arterial blood pressure. CONCLUSION: the dietary supplement analyzed in the present study failed to increase nitric oxide endogenous production.