The Study of Glycative and Oxidative Stress in Type 1 Diabetes Patients in Relation to Circulating TGF-Beta1, VCAM-1 and Diabetic Vascular Complications

Abstract Aims NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe−/−) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. Methods and results Six-week-old male Apoe−/− and eET-1/Apoe−/− mice with or without Nox1 (Nox1−/y) or Nox4 knockout (Nox4−/−) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe−/− mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe−/− and eET-1/Apoe−/−/Nox4−/− mice but not eET-1/Apoe−/−/Nox1y/− mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe−/− mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe−/− mice. Conclusion Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.

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Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes

Endocrinología Diabetes y Nutrición (English ed ) ◽

10.1016/j.endien.2019.10.003 ◽

2019 ◽

Vol 66 (9) ◽

pp. 540-549

Author(s):

Natalia Colomo ◽

Juan Pedro López-Siguero ◽

Isabel Leiva ◽

Noemí Fuentes ◽

Elehazara Rubio-Martín ◽

...

Keyword(s):

Oxidative Stress ◽

Type 1 Diabetes ◽

Glucose Control ◽

Glycemic Variability ◽

And Oxidative Stress

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Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients

Acta Endocrinologica ◽

10.1530/eje.1.02049 ◽

2006 ◽

Vol 154 (1) ◽

pp. 75-81 ◽

Cited By ~ 103

Author(s):

Lars Melholt Rasmussen ◽

Lise Tarnow ◽

Troels Krarup Hansen ◽

Hans-Henrik Parving ◽

Allan Flyvbjerg

Keyword(s):

Blood Pressure ◽

Type 1 Diabetes ◽

Systolic Blood Pressure ◽

Kidney Function ◽

Vascular Complications ◽

Diabetic Patients ◽

Diabetic Vascular Complications ◽

Patients With Diabetes ◽

Type 1 Diabetic Patients

Objective: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes. Methods: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA. Results: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49–3.99) vs 2.57 (2.19–3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine. Conclusion: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.

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