Enhanced Lipid Peroxidation and Platelet Activation in the Early Phase of Type 1 Diabetes Mellitus

Davı̀, Giovanni; Chiarelli, Francesco; Santilli, Francesca; Pomilio, Mariapina; Vigneri, Sergio; Falco, Angela; Basili, Stefania; Ciabattoni, Giovanni; Patrono, Carlo

doi:10.1161/01.cir.0000074205.17807.d0

Cited by 134 publications

(81 citation statements)

References 37 publications

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“…In some of these patients, oxidative stress and platelet activation were reduced after 1 year, coincident with a fall in the systemic levels of IL-6 and TNF-a. Thus, it appears that biochemical signals of oxidative stress and platelet activation can be appreciated early at the onset of diabetes mellitus and that their variable intensity is driven, at least in part, by IL-6 production and disease duration [57]. This finding is also consistent with the hypothesis that in children with T1DM the early increase in oxidative stress and platelet activation may be associated with inflammatory events that precede clinical manifestation of the disease.…”

Section: Oxidative Stresssupporting

confidence: 73%

“…Thus, it was suggested that changes in the rate of arachidonate peroxidation to form biologically active isoeicosanoids, such as 8-iso-PGF 2a , may represent an important biochemical link between altered glycemic control, oxidant stress and platelet activation in T2DM [28]. Interestingly, enhanced lipid peroxidation and platelet activation represent early events in the development of T1DM in children and adolescents [57]. Subjects with newly diagnosed diabetes had significantly increased urinary excretion of both 8-iso-PGF 2a and 11-dehydro-TXB 2 and higher plasma levels of a number of inflammatory markers.…”

Section: Oxidative Stressmentioning

confidence: 99%

“…For example, plasma TNF-a concentration is related to insulin resistance, and it falls with dietary restriction and weight loss [66], whereas IL-6 and C-reactive protein (CRP) are known to be increased in T2DM [67]. All of them may induce a phenotypic change of endothelial cells and/or monocytes, leading to increased production of tissue factor (TF), the major procoagulant found in atherosclerotic plaques along with alterations in soluble coagulation and fibrinolytic factors [57,59,68].…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

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Platelet activation in type 2 diabetes mellitus

Ferroni¹,

Basili

Falco

et al. 2004

Journal of Thrombosis and Haemostasis

397

288

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The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, prothrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. © 2004 International Society on Thrombosis and Haemostasis

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Section: Oxidative Stresssupporting

confidence: 73%

Section: Oxidative Stressmentioning

confidence: 99%

Section: Endothelial Dysfunctionmentioning

confidence: 99%

See 1 more Smart Citation

Platelet activation in type 2 diabetes mellitus

Ferroni¹,

Basili

Falco

et al. 2004

Journal of Thrombosis and Haemostasis

397

288

View full text Add to dashboard Cite

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“…(23) reported that acute hyperglycemia was associated with increased levels of IL6, IL4, and IL1, and these elevated levels persisted for at least 2 h after glucose control. On the other hand, a number of studies have found no such associations (16,24,25). The lack of correlation between inflammatory bioma rkers and levels of fasting glucose or HbA1c may sug gest that, once triggered, inflammatory response can be modulated positively or negatively by parameters other than those studied, including, for example, glucose excursions (12).…”

Section: Discussionmentioning

confidence: 98%

“…In addition, ROS triggers an inflammatory cascade by means of the production of proinflamma tory cytokines, such as IL6, which are involved in the pathogenesis of micro and macrovascular complica tions. Indeed, these signaling cytokines are often em ployed as markers of the inflammatory response (16).…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and interleukin-6 secretion during the progression of type 1 diabetes

Reis

Amaral

Volpe

et al. 2012

Arq Bras Endocrinol Metab

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Objective: To evaluate inflammatory, oxidizing, and reducing responses during the progression of type 1 diabetes mellitus (T1DM) in patients without chronic complications. Subjects and methods: Plasma antioxidant status, reactive oxygen species (ROS), and interleukin-6 (IL-6) were measured in 42 patients with T1DM and in 24 healthy subjects. Results: Significant increases were detected in the median values of ROS and IL-6 in patients with T1DM compared with healthy subjects (ROS ~ 4,836 vs. 2,036 RLU/min, respectively; P < .05: IL-6 ~ 14.2 vs. 9.7 pg/mL, respectively; P = .002). No significant between-group differences (P > 0.05) were observed in oxidizing responses or in IL-6 concentrations when diabetic patients were grouped according to time after diagnosis (0 -10, 10 -20 and > 20 years). Plasma antioxidant responses were similar in patients with T1DM and in healthy subjects. Conclusions: Our results demonstrate that oxidizing and inflammatory responses are increased at the onset of T1DM, but remain unchanged during disease progression. These findings suggest that functional changes involved in diabetic complications may commence in the first years after diagnosis. Arq Bras Endocrinol Metab.2012;56(7):441-8 Keywords Type 1 diabetes; disease progression; oxidative stress; plasma antioxidant status RESUMO Objetivo: Avaliar as respostas inflamatória, oxidativa e redutora na progressão do diabetes melito tipo 1 (DM1) em pacientes sem complicações crônicas. Sujeitos e métodos: Capacidade antioxidante do plasma, espécies reativas de oxigênio (ROS) e interleucina-6 (IL-6) foram avaliadas em 42 pacientes com DM1 e 24 indivíduos saudáveis. Resultados: Aumentos significativos foram detectados nas medianas de ROS e IL-6 em pacientes com DM1 comparados com indiví-duos saudáveis (ROS ~ 4.836 vs. 2.036 RLU/min, respectivamente, P < 0,05: IL-6 ~ 14,2 vs. 9,7 pg/ mL, respectivamente, P = 0,002). Diferenças não significativas (P > 0,05) foram observadas na resposta oxidante e IL-6 quando os diabéticos foram agrupados de acordo com o tempo após o diagnóstico (0-10, 10-20 e > 20 anos). A resposta antioxidante do plasma foi semelhante em pacientes com DM1 e em indivíduos saudáveis. Conclusões: Nossos resultados demonstram que as respostas oxidante e inflamatória estão aumentadas desde o início do DM1, mas mantêm-se inalteradas durante a progressão da doença, sugerindo que as mudanças funcionais envolvidas nas complicações diabéticas podem começar nos primeiros anos após o diagnóstico. Arq Bras Endocrinol Metab. 2012;56(7):441-8 Descritores Diabetes tipo 1; progressão da doença; estresse oxidativo; capacidade oxidante do plasma

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