Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome

Esposito, Katherine; Ciotola, Miryam; Carleo, Diego; Schisano, Bruno; Saccomanno, F.; Sasso, Ferdinando Carlo; Cozzolino, Domenico; Assaloni, Roberta; Merante, Domenico; Ceriello, Antonio; Giugliano, Dario

doi:10.2337/dc05-2174

Cited by 101 publications

(40 citation statements)

References 43 publications

(29 reference statements)

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“…149, 167 ACE-inhibitors and angiotensin receptor blockers are also preferred medication in diabetes mellitus. 168 Diabetes modulating drugs like metformin 169 or glitazones 170, 171 may also improve vascular function in patients with type 2 diabetes, however, the later may have negative effects on cardiovascular risk, 172 thus limiting its use.…”

Section: Clinical Implications Of Endothelial Dysfunction In Populatimentioning

confidence: 99%

The Assessment of Endothelial Function

et al. 2012

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The discovery of the endothelium as a crucial organ for the regulation of the vasculature to physiological needs and the recognition of endothelial dysfunction as a key pathological condition - which is associated with most if not all cardiovascular risk factors - led to a tremendous boost of endothelial research in the past 3 decades. Despite the possibility to measure endothelial function in the individual and its widespread use in research, its use as a clinical tool in daily medicine is not established yet. We review the most common methods to assess vascular function in humans and discuss their advantages and disadvantages. Furthermore we give an overview about clinical settings were endothelial function measurements may be valuable in individual patients. Specifically, we provide information why endothelial function is not only a risk marker for cardiovascular risk but may also provides prognostic information beyond commonly used risk scores in primary prevention, and in patients with already established coronary disease. We conclude, that non-invasive endothelial function measurements provide valuable additional information, however, to ascertain its use for daily clinical practice, future research should determine whether endothelial function can be used to guide treatment in the individual and if this translates into better outcomes.

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Section: Clinical Implications Of Endothelial Dysfunction In Populatimentioning

confidence: 99%

The Assessment of Endothelial Function

et al. 2012

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“…PPARγ activation also promotes fat storage in adipocytes and decreases adipose tissue lipolysis thereby decreasing the concentration of fatty acids presented to the liver. In addition to its metabolic effects, TZDs are also thought to decrease inflammation and cytokine production in patients with metabolic syndrome [78,79]. Various studies conducted in rodents have clearly demonstrated improvement in metabolic profiles with improved insulin sensitivity after treatment with TZDs.…”

Section: Pparγmentioning

confidence: 99%

PPARs and nonalcoholic fatty liver disease

2017

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Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver pathology ranging from simple steatosis to varying degrees of inflammation, hepatocyte injury and fibrosis. Without intervention it can progress to end-stage liver disease and hepatocellular carcinoma. Given its close association with obesity, the prevalence of NAFLD has increased dramatically worldwide. Currently, there are no FDA-approved medications for the treatment of NAFLD and although lifestyle modifications with appropriate diet and exercise have been shown to be beneficial, this has been difficult to achieve and sustain for the majority of patients. As such, the search for effective therapeutic agents is an active area of research. Peroxisome proliferator-activated receptors (PPARs) belong to a class of nuclear receptors. Because of their key role in the transcriptional regulation of glucose and lipid metabolism, PPAR ligands have been investigated as possible therapeutic agents for NAFLD. Here we review the current evidence from preclinical and clinical studies investigating the therapeutic potential of PPAR ligands for the treatment of this spectrum of liver disorders.

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“…These agents produce concurrent improvements in insulin sensitivity and vascular function in Type 2 diabetes and related states of insulin resistance [47-49,44,50-53,45]. The exact mechanism of these beneficial effects is debated, with many studies invoking mechanisms of benefit beyond improvements in insulin resistance [47,50,52,54-59,53]. Pioglitazone improved insulin-mediated vasodilation in one study where this was directly assessed.…”

Section: Therapies That Target the Endotheliummentioning

confidence: 99%

The vascular endothelium in diabetes—a therapeutic target?

Mather

2013

Rev Endocr Metab Disord

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Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

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Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome

Cited by 101 publications

References 43 publications

The Assessment of Endothelial Function

The Assessment of Endothelial Function

PPARs and nonalcoholic fatty liver disease

The vascular endothelium in diabetes—a therapeutic target?

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