Diabetic Atherosclerosis - Pathology
Insulin Resistance -
updated: 15 March 2008
The impact of insulin resistance on endothelial function, progenitor cells and repair.
Diab Vasc Dis Res. 2007 Jun;4(2):103-11.
Cubbon RM, Rajwani A, Wheatcroft SB.
The structural and functional integrity of the vascular endothelium plays a critical role in vascular homeostasis. Insulin resistance, an important risk factor for cardiovascular disease, is thought to promote atherosclerosis through a reciprocal relationship with endothelial dysfunction. In health, cumulative damage to endothelial cells incurred by exposure to risk factors is mitigated by endogenous reparative processes. Disruption of the balance between endothelial damage and repair may mediate atherosclerotic progression. Bone marrow-derived 'endothelial progenitor cells' (EPC) have been identified as significant contributors to endogenous vascular repair. Insulin resistance is associated with a spectrum of biochemical abnormalities which have the potential to reduce the availability of EPCs and diminish their capacity for vascular repair. Many lifestyle and pharmacological interventions which improve insulin resistance also increase the numbers and functionality of EPCs. Cell-based therapies may also hold promise for the prevention and treatment of cardiovascular disease.
Publication Types:
Online - Article
Atherosclerosis in diabetes and insulin resistance
Diabetes Obes Metab. 2007 Jul;9(4):455-63
Reusch JE, Draznin BB.
Atherosclerosis and cardiovascular disease are the major causes of morbidity and mortality in patients with diabetes and those with insulin resistance and the metabolic syndrome. Both conditions profoundly accelerate the development of atherosclerosis and increase the morbidity and mortality of cardiovascular events. The question, therefore, is what are the molecular/biochemical mechanisms that underlie the potentiating influence of diabetes, the metabolic syndrome and/or insulin resistance on the development and progression of atherosclerosis? The following review will focus on the molecular mechanism whereby hyperglycaemia and/or hyperinsulinemia either directly or indirectly promote atherosclerosis.
Publication Types:
Online - Abstract
Atherosclerosis in type 2 diabetes mellitus and insulin resistance: mechanistic links and therapeutic targets
J Diabetes Complications. 2002 Nov-Dec;16(6):401-15
Plutzky J, Viberti G, Haffner S.
The ongoing heavy burden of cardiovascular disease associated with diabetes mellitus highlights the failure of current treatment strategies to address effectively the cardiovascular risk profile in such patients. Insulin resistance is not only an underlying feature in most cases of type 2 diabetes, but is also associated, through the Insulin Resistance Syndrome, with cardiovascular risk factors that promote atherothrombosis through diverse mechanisms. Growing evidence suggests that treatment with anti-diabetic agents that improve insulin sensitivity, such as the thiazolidinediones, improve multiple components of the Insulin Resistance Syndrome, have beneficial effects on various atherothrombotic mechanisms, and reduce atherosclerosis in animal models and perhaps humans as well. Given data implicating chronic inflammation as a central feature of atherosclerosis, the anti-inflammatory activity of the thiazolidinediones may contribute to their potential anti-atherosclerotic effects. An improved understanding of the mechanisms linking diabetes, atherosclerosis, and cardiovascular disease is needed in order to understand how these and other current and emerging therapies might reduce diabetes-associated cardiovascular disease.
Publication Types:
Online - Abstract
Insulin resistance and atherosclerosis
Endocr Rev. 2006 May;27(3):242-59. Epub 2006 Feb 21
Nigro J, Osman N, Dart AM, Little PJ.
The epidemic of obesity in the developed world over the last two decades is driving a large increase in type 2 diabetes and consequentially setting the scene for an impending wave of cardiovascular morbidity and mortality. It is only now being recognized that the major antecedent of type 2 diabetes, insulin resistance with its attendant syndrome, is the major underlying cause of the susceptibility to type 2 diabetes and cardiovascular disease. In metabolic tissues, insulin signaling via the phosphatidylinositol-3-kinase pathway leads to glucose uptake so that in insulin resistance a state of hyperglycemia occurs; other factors such as dyslipidemia and hypertension also arise. In cardiovascular tissues there are two pathways of insulin receptor signaling, one that is predominant in metabolic tissues (mediated by phosphatidylinositol-3-kinase) and another being a growth factor-like pathway (mediated by MAPK); the down-regulation of the former and continued activity of the latter pathway leads to atherosclerosis. This review addresses the metabolic consequences of the insulin resistance syndrome, its relationship with atherosclerosis, and the impact of insulin resistance on processes of atherosclerosis including insulin signaling in cells of the vasculature.
Publication Types:
Online - Article
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