Low Endogenous Secretory Receptor for Advanced Glycation End-Products Levels Are Associated With Inflammation and Carotid Atherosclerosis in Prediabetes
Antonino Di Pino,Francesca Urbano,Rose Maria Zagami,Agnese Filippello,Stefania Di Mauro,Salvatore Piro,Francesco Purrello,Agata Maria Rabuazzo +7 more
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Subjects with HbA1c prediabetes exhibited significantly reduced esRAGE levels and increased levels of markers of inflammation, which are associated with early markers of cardiovascular disease.Abstract:
Context: Prediabetes is associated with atherosclerotic vascular damage. Objective: We investigated the correlation of endogenous secretory receptor for advanced glycation end-products (esRAGE), total soluble RAGE (sRAGE) and markers of inflammation, with early cardiovascular disease in subjects with prediabetes. We particularly focused on individuals with prediabetes identified only by glycated hemoglobin A1c (HbA1c) (5.7–6.4%) who had normal fasting glucose and were normotolerant after oral glucose tolerance test. Design: This was a cross-sectional study. Setting: The study was conducted in the Department of Clinical and Molecular Medicine, University of Catania, Italy. Main Outcome Measure: sRAGE, esRAGE, carboxymethyl-lysine, S100A12, HbA1c, fasting glycemia, oral glucose tolerance test, pulse wave velocity, and intima-media thickness were evaluated in subjects with prediabetes. Patients: Three hundred eighty subjects without previous history of diabetes were stratified into three groups: controls (n ...read more
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Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents.
TL;DR: The role of insulin resistance and the IRS in the development of atherosclerotic cardiovascular disease and the impact of the insulin sensitizing agents and of other antihyperglycemic medications on cardiovascular outcomes is discussed.
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Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis
TL;DR: Pioglitazone was associated with reduced risk of MACE in people with insulin resistance, pre-diabetes and diabetes mellitus, however, the risks of heart failure, bone fracture, oedema and weight gain were increased.
Journal ArticleDOI
Receptor for Advanced Glycation End Products (RAGE) and Mechanisms and Therapeutic Opportunities in Diabetes and Cardiovascular Disease: Insights From Human Subjects and Animal Models.
Lander Egaña-Gorroño,Raquel López-Díez,Gautham Yepuri,Lisa Ramirez,Sergey Reverdatto,Paul F. Gugger,Alexander Shekhtman,Ravichandran Ramasamy,Ann Marie Schmidt +8 more
TL;DR: Current knowledge regarding the roles for RAGE and DIAPH1 in the causes and consequences of diabetes, from obesity to CVD is presented and a new target for therapeutic interruption of RAGE signaling is highlighted.
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Advanced glycation end products and their receptor in age-related, non-communicable chronic inflammatory diseases; Overview of clinical evidence and potential contributions to disease
TL;DR: It can be concluded that these AGE-RAGE disturbances are a common contributing factor to the inflammatory state and pathogenesis of these various conditions.
Journal ArticleDOI
High intake of dietary advanced glycation end-products is associated with increased arterial stiffness and inflammation in subjects with type 2 diabetes
A. Di Pino,Walter Currenti,Francesca Urbano,Roberto Scicali,Salvatore Piro,Francesco Purrello,Agata Maria Rabuazzo +6 more
TL;DR: It is suggested that a chronic high dAGE diet could lead to a vascular dysfunction and inflammatory activation, contributing to the development of vascular complications in subjects with type 2 diabetes.
References
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Journal ArticleDOI
Diagnosis and Classification of Diabetes Mellitus
TL;DR: The chronic hyperglycemia of diabetes is associated with long-term damage, dys-function, and failure of differentorgans, especially the eyes, kidneys, nerves, heart, and blood vessels.
Journal ArticleDOI
Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts.
Lisa Park,Kathleen G. Raman,Kenneth J. Lee,Yan Lu,Luis J. Ferran,Wing Sun Chow,David M. Stern,Ann Marie Schmidt +7 more
TL;DR: Findings indicate interaction between the advanced glycation endproducts and their receptor is involved in the development of accelerated atherosclerosis in diabetes, and identify this receptor as a new therapeutic target in diabetic macrovascular disease.
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Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention
Abstract: A workshop was convened by the International Diabetes Federation to review the latest information relating to the risks associated with impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) for future diabetes and cardiovascular disease (CVD). The workshop sought to address three questions: (i) are the current definitions of IGT and IFG appropriate; (ii) are IFG and IGT risk factors, risk markers or diseases; (iii) what interventions (if any) should be recommended for people with IFG and IGT? The determinants of elevated fasting glucose and 2-h plasma glucose in an oral glucose tolerance test (2-HPG) levels differ. Raised hepatic glucose output and a defect in early insulin secretion are characteristic of the former, and peripheral insulin resistance is most characteristic of the latter. Therefore, it is not surprising that the concordance between the categories of IFG and IGT is limited. In all prevalence studies to date only half or less of people with IFG have IGT, and even a lower proportion (20-30%) with IGT also have IFG. In the majority of populations studied, IGT is more prevalent than IFG, and there is a difference in phenotype and gender distribution between the two categories. IFG is substantially more common amongst men and IGT slightly more common amongst women. The prevalence of IFG tends to plateau in middle age whereas the prevalence of IGT rises into old age. Both IFG and IGT are associated with a substantially increased risk of developing diabetes, with the highest risk in people with combined IFG and IGT. Because IGT is commoner than IFG in most populations it is more sensitive (but slightly less specific) for identifying people who will develop diabetes. In most populations studied, 60% of people who develop diabetes have either IGT or IFG 5 years or so before, with the other 40% having normal glucose tolerance at that time. The limited published data suggest that both isolated IFG (I-IFG) and isolated IGT (I-IGT) are similarly associated with cardiovascular risk factors, such as hypertension and dyslipidaemia, with the highest risk in those with combined IFG and IGT. However, some data have suggested that I-IGT is more strongly associated with hypertension and dyslipidaemia (features of the metabolic syndrome) than I-IFG. In unadjusted analyses both IFG and IGT are associated with CVD and total mortality. In separate analyses for fasting and 2-HPG adjusted for other cardiovascular risk factors (from the DECODE study) there remains a continuous relationship between 2-HPG and mortality, but an independent relationship with fasting glucose is only found above 7.0 mmol/l. Glycated haemoglobin (HbA1c) levels are continuously and positively associated with CVD and total mortality independent of other CVD risk factors. Life style interventions, including weight loss and increased physical activity, are highly effective in preventing or delaying the onset of diabetes in people with IGT. Two randomized controlled trials of individuals with IGT found that life style intervention studies reduce the risk of progressing to diabetes by 58%. The oral hypoglycaemic drugs metformin and acarbose have also been shown to be effective, but less so than the life style measures. Similar data do not yet exist for the effectiveness of such interventions in people with I-IFG. Larger studies are required to evaluate the effects of interventions on cardiovascular outcomes in people with IGT. Cost effective strategies to identify people with IGT for intervention should be developed and evaluated. The use of simple risk scores to assess who should undergo an oral glucose tolerance test is one promising approach, although these will need to be population-specific. In conclusion, IGT and IFG differ in their prevalence, population distribution, phenotype, and risk of total mortality and CVD. The consensus of the workshop was: 1. The diagnostic thresholds for all categories of glucose intolerance should be revisited in the light of the latest evidence. There was no clear consensus (with current evidence) on whether IFG and IGT should be classified as diseases, but they clearly represent risk factors and risk markers for diabetes and CVD, respectively. 2. Both IGT and IFG are similarly associated with an increased risk of diabetes, but IGT is more strongly associated with CVD outcomes. 3. Risks are higher when IGT and IFG coexist. 4. Life style interventions are highly effective in delaying or preventing the onset of diabetes in people with IGT and may reduce CVD and total mortality, but the latter requires formal testing.
Journal ArticleDOI
Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation
Ravichandran Ramasamy,Susan J. Vannucci,Shirley ShiDu Yan,Kevan C. Herold,Shi Fang Yan,Ann Marie Schmidt +5 more
TL;DR: It is hypothesized that AGEs cause perturbation in a diverse group of diseases, such as diabetes, inflammation, neurodegeneration, and aging, and it is proposed that targeting this pathway may represent a logical step in the prevention/treatment of the sequelae of these disorders.
Journal ArticleDOI
Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury.
Hideto Yonekura,Yasuhiko Yamamoto,Shigeru Sakurai,Ralica G Petrova,Md. Joynal Abedin,Hui Li,Kiyoshi Yasui,Masayoshi Takeuchi,Zenji Makita,Shin Takasawa,Hiroshi Okamoto,Takuo Watanabe,Hiroshi Yamamoto +12 more
TL;DR: The AGE induction of extracellular-signal-related kinase phosphorylation and vascular endothelial growth factor in EC and of the growth and cord-like structure formation of EC was abolished completely by C-truncated RAGE, indicating that this endogenous secretory receptor (endogenous secretory RAGE) is cytoprotective against AGE.