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Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.

Forst T, Weber MM, Pfützner A - Exp Diabetes Res (2012)

Bottom Line: Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality.Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies.The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical Research and Development, 55116 Mainz, Germany. thomasf@ikfe.de

ABSTRACT
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

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Related in: MedlinePlus

Schematic illustration of the central role of visceral adipose tissue in the generation of the atherogenic environment in obese patients. Visceral adipose tissue induces insulin resistance, thereby increasing insulin and proinsulin release from the beta cell. Unphysiological levels of insulin and proinsulin promote atherogenesis through the activation of endothelial MAPK. Preadipocytes secrete numerous adipocytokines involved in the pathogenesis of hypertension, dyslipidemia, and inflammation. (MAPK: mitogen-activated protein kinase, IL-6: interleukin-6, TNFα: tumor necrosis factor α, FFA: free fatty acids).
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fig1: Schematic illustration of the central role of visceral adipose tissue in the generation of the atherogenic environment in obese patients. Visceral adipose tissue induces insulin resistance, thereby increasing insulin and proinsulin release from the beta cell. Unphysiological levels of insulin and proinsulin promote atherogenesis through the activation of endothelial MAPK. Preadipocytes secrete numerous adipocytokines involved in the pathogenesis of hypertension, dyslipidemia, and inflammation. (MAPK: mitogen-activated protein kinase, IL-6: interleukin-6, TNFα: tumor necrosis factor α, FFA: free fatty acids).

Mentions: Adipose tissue is assumed to play an integral role in the pathogenesis of vascular dysfunction and the development of T2DM [12]. As maturing pre-adipocytes differentiate to become adult adipocytes, they acquire the ability to synthesize hundreds of proteins. Adipose tissue releases a large number of cytokines and bioactive mediators with endocrine, autocrine, juxtacrine, and paracrine activity. These proinflammatory adipocytokines include TNF-α, IL-6, leptin, plasminogen activator inhibitor 1 (PAI-1), angiotensinogen, resistin, and c-reactive protein, all of them well known to interfere with insulin sensitivity, blood pressure regulation, lipid metabolism, and inflammation (Figure 1). On the other hand, the release of adiponectin, an anti-inflammatory and vasoprotective adipokine, is reduced in insulin-resistant obese patients and in patients with T2DM [13]. In addition, it is likely that many more undiscovered fat cell-derived mediators are causally involved in cardiovascular health, insulin resistance, and the development of T2DM.


Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.

Forst T, Weber MM, Pfützner A - Exp Diabetes Res (2012)

Schematic illustration of the central role of visceral adipose tissue in the generation of the atherogenic environment in obese patients. Visceral adipose tissue induces insulin resistance, thereby increasing insulin and proinsulin release from the beta cell. Unphysiological levels of insulin and proinsulin promote atherogenesis through the activation of endothelial MAPK. Preadipocytes secrete numerous adipocytokines involved in the pathogenesis of hypertension, dyslipidemia, and inflammation. (MAPK: mitogen-activated protein kinase, IL-6: interleukin-6, TNFα: tumor necrosis factor α, FFA: free fatty acids).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3345223&req=5

fig1: Schematic illustration of the central role of visceral adipose tissue in the generation of the atherogenic environment in obese patients. Visceral adipose tissue induces insulin resistance, thereby increasing insulin and proinsulin release from the beta cell. Unphysiological levels of insulin and proinsulin promote atherogenesis through the activation of endothelial MAPK. Preadipocytes secrete numerous adipocytokines involved in the pathogenesis of hypertension, dyslipidemia, and inflammation. (MAPK: mitogen-activated protein kinase, IL-6: interleukin-6, TNFα: tumor necrosis factor α, FFA: free fatty acids).
Mentions: Adipose tissue is assumed to play an integral role in the pathogenesis of vascular dysfunction and the development of T2DM [12]. As maturing pre-adipocytes differentiate to become adult adipocytes, they acquire the ability to synthesize hundreds of proteins. Adipose tissue releases a large number of cytokines and bioactive mediators with endocrine, autocrine, juxtacrine, and paracrine activity. These proinflammatory adipocytokines include TNF-α, IL-6, leptin, plasminogen activator inhibitor 1 (PAI-1), angiotensinogen, resistin, and c-reactive protein, all of them well known to interfere with insulin sensitivity, blood pressure regulation, lipid metabolism, and inflammation (Figure 1). On the other hand, the release of adiponectin, an anti-inflammatory and vasoprotective adipokine, is reduced in insulin-resistant obese patients and in patients with T2DM [13]. In addition, it is likely that many more undiscovered fat cell-derived mediators are causally involved in cardiovascular health, insulin resistance, and the development of T2DM.

Bottom Line: Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality.Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies.The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical Research and Development, 55116 Mainz, Germany. thomasf@ikfe.de

ABSTRACT
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

Show MeSH
Related in: MedlinePlus