To test the hypothesis that: (i) functional microvascular dilator capacity is independently associated with insulin sensitivity and age in individuals with central adiposity at risk of cardiovascular disease (CVD); and (ii) functional microvascular dilator capacity is improved by high dose statin treatment.
Functional dilator capacity (measured as change in laser Doppler blood flux from baseline during post occlusive reactive hyperemia [peak flux%resting flux; PF%RF] and flowmotion (power spectral density [PSD] analysis)) were assessed in 40 people with central adiposity and one or more other CVD risk factors. Measurements were made at rest and during acute hyperinsulinaemia before and six months after high dose atorvastatin (40 mg daily) or placebo.
Insulin-induced change in PF%RF was independently associated with insulin sensitivity (M/I) (r = 0.46 p = 0.02) and age (r = -0.46 p = 0.02), which together explained almost half of the variance in PF%RF (adjusted r² = 0.37, p = 0.008). Whilst atorvastatin decreased LDL cholesterol by 51% (p < 0.001), PF%RF and flowmotion remained unchanged.
Insulin sensitivity and age are independently associated with an insulin-induced change in functional microvascular dilator capacity in individuals with central adiposity at risk of CVD. Dilator capacity is not improved by six months high dose statin treatment.
"Recently, the cutaneous circulation has emerged as an accessible and potentially representative vascular bed in which to examine the mechanisms that control microvascular function. It has been argued that pathologyinduced changes in cutaneous microvascular function may reflect those occurring in less accessible vascular beds and thus provide a useful surrogate in which to investigate deficits in microvascular function (Holowatz et al. 2008), including those found in obesity-associated insulin resistance (Clough et al. 2011; De Boer et al. 2012), diabetes (Clough et al. 2011), hypertension, (Gryglewska et al. 2010; Rossi et al. 2011) and ageing (Gooding et al. 2006; Avery et al. 2009) and in smokers (Avery et al. 2009). Laser Doppler flowmetry is a widely used non-invasive method used to assess dynamic changes in blood flux in response to vasoreactive stimuli in both health and disease (Roustit & Cracowski, 2012). "
[Show abstract][Hide abstract] ABSTRACT: New Findings• What is the central question of this study? Autonomic nervous dysfunction is implicated in complications of sickle cell anaemia (SCA). In healthy adults, a deep inspiratory breath hold (IBH) elicits rapid transient SNS‐ mediated vasoconstriction detectable using Laser Doppler Flux (LDF) assessment of the finger‐tip cutaneous micovasculature. • What is the main finding and its importance? We demonstrate significantly increased resting peripheral blood flow and sympathetic activity in African children with SCA compared to sibling controls and increased sympathetic stimulation in response to vasoprovocation with DIG.This study is the first to observe an inverse association between resting peripheral blood flow and haemoglobin oxygen saturation (SpO2). These phenomena may be an adaptive response to the hypoxic exposure in SCA.
[Show abstract][Hide abstract] ABSTRACT: Please cite this paper as: Clough and Norman (2011). The Microcirculation: A Target for Developmental Priming. Microcirculation 18(4), 286–297.
There is increasing evidence that the early life environment, of which nutrition is a key component, acts through developmental adaptations to set the capacity of cardiovascular and metabolic pathways, and ultimately the limits to physiological challenges in later life. Suboptimal maternal nutrition and fetal growth result in reduced microvascular perfusion and functional dilator capacity, which are strongly associated with later development of obesity, type 2 diabetes, and hypertension. These conditions are also linked to microvascular rarefaction and remodeling that together limit capillary recruitment, reduce exchange capacity and increase diffusion distances of metabolic substrates, and increase local and overall peripheral resistance. Changes in small vessel structure and function may be seen very early, long before the onset of overt cardiovascular and metabolic disease, and may thus be a target for early therapeutic and lifestyle intervention strategies. This article explores how a disadvantageous microvascular phenotype may result from perinatal priming and how developmental plasticity may become an important and additional risk determinant in susceptibility to cardiometabolic disease in adult life.
Microcirculation (New York, N.Y.: 1994) 02/2011; 18(4):286-97. DOI:10.1111/j.1549-8719.2011.00087.x · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of type 2 diabetes mellitus (T2DM) and its major risk factor, obesity, has reached epidemic proportions in Western society. How obesity leads to insulin resistance and subsequent T2DM is incompletely understood. It has been established that insulin can redirect blood flow in skeletal muscle from non-nutritive to nutritive capillary networks, without increasing total blood flow. This results in a net increase of the overall number of perfused nutritive capillary networks and thereby increases insulin-mediated glucose uptake by skeletal muscle. This process, referred to as functional (nutritive) capillary recruitment, has been shown to be endothelium-dependent and to require activation of the phosphatidylinositol-kinase (PI3K) pathway in the endothelial cell. Several studies have demonstrated that these processes are impaired in states of microvascular dysfunction. In obesity, changes in several adipokines are likely candidates to influence insulin signaling pathways in endothelial cells, thereby causing microvascular dysfunction. Microvascular dysfunction, in turn, impairs the timely access of glucose and insulin to their target tissues, and may therefore be an additional cause of insulin resistance. Thus, microvascular dysfunction may be a key feature in the development of obesity-related insulin resistance. In the present review, we will discuss the evidence for this emerging role for the microcirculation as a possible link between obesity and insulin resistance.
Reviews in Endocrine and Metabolic Disorders 01/2013; 14(1). DOI:10.1007/s11154-012-9231-7 · 4.89 Impact Factor
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