Cardiovasc Diabetol
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Cardiovasc Diabetol · Jan 2015
ReviewCrosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications.
Advanced glycation end products (AGEs) consist of heterogenous group of macroprotein derivatives, which are formed by non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids, and whose process has progressed at an accelerated rate under diabetes. Non-enzymatic glycation and cross-linking of protein alter its structural integrity and function, contributing to the aging of macromolecules. Furthermore, engagement of receptor for AGEs (RAGE) with AGEs elicits oxidative stress generation and subsequently evokes proliferative, inflammatory, and fibrotic reactions in a variety of cells. ⋯ Since GLP-1 and GIP are rapidly degraded and inactivated by dipeptidyl peptidase-4 (DPP-4), inhibition of DPP-4 and/or DPP-4-resistant GLP-1 analogues have been proposed as a potential target for the treatment of diabetes. Recently, DPP-4 has been shown to cleave multiple peptides, and blockade of DPP-4 could exert diverse biological actions in GLP-1- or GIP-independent manner. This article summarizes the crosstalk between AGEs-RAGE axis and DPP-4-incretin system in the development and progression of diabetes-associated disorders and its therapeutic intervention, especially focusing on diabetic vascular complications.
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Cardiovasc Diabetol · Jan 2015
Comparative StudySensitivity of various adiposity indices in identifying cardiometabolic diseases in Arab adults.
Obesity is a recognized risk factor for various cardiometabolic diseases and several indices are used clinically to assess overall cardiometabolic risk. This study aims to determine the sensitivity of six anthropometric indices [Body mass index (BMI), waist, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI) and visceral adiposity index (VAI)] in determining diabetes mellitus type 2, coronary heart disease, dyslipidemia, hypertension and metabolic syndrome (MetS) in Saudi adults recruited from two independent cohorts (2008-2009 and 2013-2014). ⋯ Sensitivity of adiposity indices regarding cardiometabolic diseases highlight the importance of body fat distribution in determining overall cardiometabolic risk, with indices involving abdominal obesity being more clinically significant than BMI and BAI. The sensitivity of these adiposity indices should be noted in assessing a particular cardiometabolic disease.
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Cardiovasc Diabetol · Jan 2015
Normal-weight obesity is associated with increased risk of subclinical atherosclerosis.
Subjects with normal body mass index (BMI) but elevated amounts of body fat (normal-weight obesity; NWO) show cardiometabolic dysregulation compared to subjects with normal BMI and normal amounts of body fat (normal-weight lean; NWL). In this study, we aimed to evaluate whether NWO individuals have higher rates of subclinical atherosclerosis compared to NWL subjects. ⋯ NWO individuals carry a higher incidence of subclinical atherosclerosis compared with NWL individuals, regardless of other clinical risk factors for atherosclerosis.
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Cardiovasc Diabetol · Jan 2015
Tissue inflammation and nitric oxide-mediated alterations in cardiovascular function are major determinants of endotoxin-induced insulin resistance.
Endotoxin (i.e. LPS) administration induces a robust inflammatory response with accompanying cardiovascular dysfunction and insulin resistance. Overabundance of nitric oxide (NO) contributes to the vascular dysfunction. However, inflammation itself also induces insulin resistance in skeletal muscle. We sought to investigate whether the cardiovascular dysfunction induced by increased NO availability without inflammatory stress can promote insulin resistance. Additionally, we examined the role of inducible nitric oxide synthase (iNOS or NOS2), the source of the increase in NO availability, in modulating LPS-induced decrease in insulin-stimulated muscle glucose uptake (MGU). ⋯ Nitric oxide excess and LPS impairs glycemic control by diminishing MGU. LPS impairs MGU by both the direct effect of inflammation on the myocyte, as well as by the indirect NO-driven cardiovascular dysfunction.
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Cardiovasc Diabetol · Jun 2014
Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum.
Diabetic patients have a significantly worse prognosis after an acute myocardial infarction (AMI) than their counterparts. Previous studies have shown that the number of circulating endothelial progenitor cells (EPCs) significantly increase early after an AMI in normoglycemic patients. However, it is well known that type 2 diabetes mellitus (DM) is associated with impaired function and reduced circulating EPCs levels. Nonetheless, few studies have analyzed EPCs response of diabetics to an AMI and the EPC response of pre-diabetic patients has not been reported yet. Therefore, we hypothesized that in the acute phase of an AMI, diabetic and pre-diabetics have lower circulating EPCs levels than patients with normal glucose metabolism. We also evaluated the possible capacity of chronic antidiabetic treatment in the recovery of EPCs response to an AMI in diabetics. ⋯ This study indicates that there is a progressive decrease in EPCs levels, from pre-diabetes to DM, in AMI patients. Moreover, glycemic control seems to be determinant for circulating EPCs levels presented in the acute phase of an AMI and chronic insulin therapy may probably attenuate the deficit in EPCs pool seen in diabetics.