Elsevier

Atherosclerosis

Volume 238, Issue 2, February 2015, Pages 370-379
Atherosclerosis

Review
Arterial stiffness in diabetes mellitus

https://doi.org/10.1016/j.atherosclerosis.2014.12.023Get rights and content

Highlights

  • Worsening arterial stiffness can be seen in the pre-diabetic state and the metabolic syndrome.

  • Arterial stiffness is closely related to diabetic nephropathy, retinopathy, and neuropathy.

  • Arterial stiffness is an independent predictor of mortality in both diabetics and non-diabetics.

Abstract

Arterial stiffness is an age-related process that is a shared consequence of numerous diseases including diabetes mellitus (DM), and is an independent predictor of mortality both in this population and in the general population. While much has been published about arterial stiffness in patients with DM, a thorough review of the current literature is lacking. Using a systematic literature search strategy, we aimed to summarize our current understanding related to arterial stiffness in DM. We review key studies demonstrating that, among patients with established DM, arterial stiffness is closely related to the progression of complications of DM, including nephropathy, retinopathy, and neuropathy. It is also becoming clear that arterial stiffness can be increased even in pre-diabetic populations with impaired glucose tolerance, and in those with the metabolic syndrome (METS), well before the onset of overt DM. Some data suggests that arterial stiffness can predict the onset of DM. However, future work is needed to further clarify whether large artery stiffness and the pulsatile hemodynamic changes that accompany it are involved in the pathogenesis of DM, and whether interventions targeting arterial stiffness are associated with improved clinical outcomes in DM. We also review of the potential mechanisms of arterial stiffness in DM, with particular emphasis on the role of advanced glycation endproducts (AGEs) and nitric oxide dysregulation, and address potential future directions for research.

Section snippets

Background

Arterial stiffness is an age-related progressive process that is a shared consequence of numerous diseases including diabetes mellitus (DM), hypertension, the metabolic syndrome (METS) and chronic kidney disease (CKD), among others. DM is as an increasingly prevalent disease with well-recognized short and long-term cardiovascular consequences. In this paper, we discuss recent findings from clinical and population-based studies assessing arterial stiffness in diabetic cohorts. There is a

Methods

We searched Medline (from 1946 to 2013) and Embase (from 1947 to 2013) databases, using detailed search strategies, as detailed in the online supplement. We developed search methods to capture publications related to arterial stiffness and DM, AGEs, and microvascular complications of DM. This search generated 1700 articles and abstracts which were reviewed in their entirety and discussed by the authors to establish their relevance to this review. When appropriate, we discuss major contributions

Human studies of DM and arterial stiffness

Arterial stiffness represents a subclinical marker of cardiovascular risk. Arterial stiffness has been shown to be an independent risk factor for adverse cardiovascular events and all-cause mortality in the general population [1]. Markers of large artery stiffness such as pulse pressure (PP), pulse wave velocity (PWV), and aortic characteristic impedance (Zc), have been widely studied over the past two decades. With improvements in techniques to non-invasively measure these hemodynamic

Arterial stiffness and microvascular/macrovascular changes in DM

This section reviews current studies examining the relationship between arterial stiffness and target organ dysfunction in DM, specifically: nephropathy, retinopathy, and neuropathy/autonomic dysfunction. Additionally, association between stiffness and cognitive dysfunction and stroke are discussed as well. Studies assessing the relationship between arterial stiffness and/or related hemodynamic indices and target organ dysfunction in type 2 DM are summarized in Table 3.

Advanced glycation end-products, nitric oxide dysregulation, and arterial stiffness

The remainder of the paper will focus on potential mechanisms of arterial stiffness in DM, with particular emphasis on the role of advanced glycation endproducts (AGEs) and nitric oxide (NO) dysregulation.

Several studies have implicated AGEs in the acceleration of age-related vascular changes and development of cardiovascular events in both diabetic and non-diabetic populations [68]. AGE formation consists of several reversible and irreversible steps that culminate in the detrimental

Conclusions

Accumulating evidence suggests that arterial stiffness is a key component in the pathogenesis of DM, and importantly, that endothelial dysfunction may even occur with early insulin resistance and impaired fasting glucose, before the development of overt DM. Both AGEs and endothelial NO dysregulation play critical roles in the pathogenesis of arterial stiffness. Arterial stiffness is an independent predictor of mortality both in the diabetic population and in the population as a whole, and

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