A 4-week high-AGE diet does not impair glucose metabolism and vascular function in obese individuals.

BACKGROUNDAccumulation of advanced glycation endproducts (AGEs) may contribute to the pathophysiology of type 2 diabetes and its vascular complications. AGEs are widely present in food, but whether restricting AGE intake improves risk factors for type 2 diabetes and vascular dysfunction is controversial.METHODSAbdominally obese but otherwise healthy individuals were randomly assigned to a specifically designed 4-week diet low or high in AGEs in a double-blind, parallel design.

Habitual Intake of Dietary Advanced Glycation End Products Is Not Associated with Arterial Stiffness of the Aorta and Carotid Artery in Adults: The Maastricht Study.

Background: Advanced glycation end products (AGEs), a heterogeneous group of bioactive compounds, are thought to contribute to arterial stiffness, which in turn is a causal factor in the pathogenesis of stroke, myocardial infarction, and heart failure. Whether AGEs derived from food also contribute to arterial stiffness is not clear.

Objectives: We investigated whether higher intake of dietary AGEs is associated with arterial stiffness.

Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake.

BACKGROUNDSalt-sensitive hypertension is often accompanied by insulin resistance in obese individuals, but the underlying mechanisms are obscure. Microvascular function is known to affect both salt sensitivity of blood pressure and metabolic insulin sensitivity. We hypothesized that excessive salt intake increases blood pressure and decreases insulin-mediated glucose disposal, at least in part by impairing insulin-mediated muscle microvascular recruitment (IMMR).

Independent tissue contributors to obesity-associated insulin resistance.

Background: Induction of insulin resistance is a key pathway through which obesity increases risk of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular events. Although the detrimental effects of obesity on insulin sensitivity are incompletely understood, accumulation of visceral, subcutaneous, and liver fat and impairment of insulin-induced muscle microvascular recruitment (MVR) may be involved. As these phenotypic changes often coincide in obesity, we aimed to unravel whether they independently contribute to insulin resistance and thus constitute separate targets for intervention.

The Link Between Adipose Tissue Renin-Angiotensin-Aldosterone System Signaling and Obesity-Associated Hypertension.

Obese individuals frequently develop hypertension, which is for an important part attributable to renin-angiotensin-aldosterone system (RAAS) overactivity. This review summarizes preclinical and clinical evidence on the involvement of dysfunctional adipose tissue in RAAS activation and on the renal, central, and vascular mechanisms linking RAAS components to obesity-associated hypertension.

Pathophysiological differences between multifocal fibromuscular dysplasia and atherosclerotic renal artery stenosis.

Background: Fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis (ARAS) are the most common causes of renovascular hypertension. So far, FMD is believed to cause hypertension via similar mechanisms as in ARAS, that is, a decrease in renal blood flow, which subsequently leads to increased renin secretion. However, given the differences in the blood pressure (BP)-lowering effect of revascularization between patients with ARAS and FMD, we questioned whether this is true.

Diet-induced weight loss improves not only cardiometabolic risk markers but also markers of vascular function: a randomized controlled trial in abdominally obese men.

Background: Many trials assessing effects of dietary weight loss on vascular function have been performed without no-weight loss control groups and in individuals with obesity-related morbidities. Usually a limited set of vascular function markers has been investigated.

Objective: The objective of this study was to examine effects of diet-induced weight loss on various vascular function markers and differences between normal-weight and abdominally obese men at baseline and after weight reduction.

Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study.

Background: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known.

Physical Activity Is Associated With Glucose Tolerance Independent of Microvascular Function: The Maastricht Study.

Context And Objective: Moderate-to-vigorous physical activity (MVPA) and physical fitness (PF) are positively associated with glucose tolerance. Such associations may be partly conditioned by microvascular function, which is a common correlate to MVPA, PF, and glucose tolerance. To test this hypothesis, the present study sought to investigate independent associations of MVPA and PF with glucose tolerance and to what extent these associations are mediated by microvascular function.

Acute eprosartan-induced intrarenal vasodilation in hypertensive humans is not influenced by dietary sodium intake or angiotensin II co-infusion.

Background: Angiotensin II (Ang II) is thought to play an important role in the development of hypertension. Nevertheless, knowledge on the angiotensin II type-1-receptors (AT1Rs) in the hypertensive kidney and the influence of sodium intake and renin-angiotensin system activity on intrarenal AT1R blockade is scarce. To improve our understanding of renal AT1Rs in hypertensive patients, we studied the effects of acute, local administration of AT1R-blocker eprosartan in kidneys of patients with essential hypertension (off medication).

Capillary Rarefaction Associates with Albuminuria: The Maastricht Study.

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction.

Uric acid and skin microvascular function: the Maastricht study.

Objective: Microvascular dysfunction has been suggested as a possible underlying mechanism for the association between uric acid and various diseases, such as hypertension, renal disease and cardiomyopathies. We therefore analysed the association between serum uric acid and skin microvascular function, a model of generalized microvascular function.

Methods: A cross-sectional study was performed in 610 individuals [51.

Growth and endothelial function in the first 2 years of life.

Objective: To test the hypothesis that the inverse association between infant growth and endothelial function at 6 months would persist to 24 months and that accelerated growth would lead to an increased percent body fat, which would, in turn, impact negatively on endothelial function.

Study Design: In a prospective observational study, 104 healthy term newborns underwent anthropometry and measurements of vascular vasodilation at 0, 6, 12, and 24 months. We recorded maximum vasodilation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) by use of laser-Doppler vascular perfusion monitoring of the forearm skin vasculature.

Association Between Arterial Stiffness and Skin Microvascular Function: The SUVIMAX2 Study and The Maastricht Study.

Background: It has been hypothesized that arterial stiffness leads to generalized microvascular dysfunction and that individuals with type 2 diabetes mellitus (T2DM) are particularly prone to the detrimental effects of arterial stiffness. However, evidence for an association between stiffness and markers of generalized microvascular dysfunction is lacking. We therefore investigated the association between arterial stiffness and skin microvascular function in individuals without and with T2DM.

Age, waist circumference, and blood pressure are associated with skin microvascular flow motion: the Maastricht Study.

Objective: Skin microvascular flow motion (SMF)--blood flow fluctuation attributed to the rhythmic contraction and dilation of arterioles--is thought to be an important component of the microcirculation, by ensuring optimal delivery of nutrients and oxygen to tissue and regulating local hydraulic resistance. There is some evidence that SMF is altered in obesity, type 2 diabetes mellitus, and hypertension. Nevertheless, most studies of SMF have been conducted in highly selected patient groups, and evidence how SMF relates to other cardiovascular risk factors is scarce.

Angiotensin-(1-7)-induced renal vasodilation is reduced in human kidneys with renal artery stenosis.

Background: Angiotensin-(1-7) modulates renal blood flow in humans with essential hypertension by inducing vasodilation and counterbalancing angiotensin II-induced vasoconstriction. Little is, however, known about the effects of angiotensin-(1-7) in kidneys with atherosclerotic renal artery stenosis. We previously demonstrated that the effect of angiotensin-(1-7) is reduced in patients with increased activity of the renin-angiotensin system.

Genetic, maternal and placental factors in the association between birth weight and physical fitness: a longitudinal twin study.

Background: Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design: Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10-18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study.

Genetic and environmental factors in associations between infant growth and adult cardiometabolic risk profile in twins.

Background: Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear.

Objective: The objective was to examine the importance of genetic and environmental factors in the associations between infant growth and adult cardiometabolic risk factors (anthropometric characteristics, lipids, insulin sensitivity, leptin, blood pressure, and fibrinogen) in twins.

Angiotensin-(1-7)-induced renal vasodilation in hypertensive humans is attenuated by low sodium intake and angiotensin II co-infusion.

Current evidence suggests that angiotensin-(1-7) plays an important role in the regulation of tissue blood flow. This evidence, however, is restricted to studies in animals and human forearm. Therefore, we studied the effects of intrarenal angiotensin-(1-7) infusion on renal blood flow in hypertensive humans.

Endothelial dysfunction in (pre)diabetes: characteristics, causative mechanisms and pathogenic role in type 2 diabetes.

Endothelial dysfunction associated with diabetes and cardiovascular disease is characterized by changes in vasoregulation, enhanced generation of reactive oxygen intermediates, inflammatory activation, and altered barrier function. These endothelial alterations contribute to excess cardiovascular disease in diabetes, but may also play a role in the pathogenesis of diabetes, especially type 2. The mechanisms underlying endothelial dysfunction in diabetes differ between type 1 (T1D) and type 2 diabetes (T2D): hyperglycemia contributes to endothelial dysfunction in all individuals with diabetes, whereas the causative mechanisms in T2D also include impaired insulin signaling in endothelial cells, dyslipidemia and altered secretion of bioactive substances (adipokines) by adipose tissue.

Microvascular dysfunction: an emerging pathway in the pathogenesis of obesity-related insulin resistance.

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.

Influence of growth during infancy on endothelium-dependent vasodilatation at the age of 6 months.

Low birth weight and accelerated infant growth are associated with cardiovascular disease in adulthood. Endothelial dysfunction is regarded as a precursor of atherosclerosis and is also related to infant growth. We aimed to examine whether an association between infant growth and endothelial function is already present during discrete periods of growth during the first 6 months of life in healthy term infants.

Microvascular dysfunction is associated with a higher incidence of type 2 diabetes mellitus: a systematic review and meta-analysis.

Objective: Recent data support the hypothesis that microvascular dysfunction may be a potential mechanism in the development of insulin resistance. We examined the association of microvascular dysfunction with incident type 2 diabetes mellitus (T2DM) and impaired glucose metabolism by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic.

Methods And Results: We searched Medline and Embase for articles published up to October 2011.

Reduced renal plasma clearance does not explain increased plasma asymmetric dimethylarginine in hypertensive subjects with mild to moderate renal insufficiency.

Plasma concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) increase already in the early stages of renal insufficiency. There is no agreement as to whether reduced renal plasma clearance (RPCL) contributes to this increase. Therefore, we investigated the relationship between estimated glomerular filtration rate (eGFR), RPCL, and plasma ADMA and SDMA in essential hypertensive patients with mild to moderate renal insufficiency.