Microcirculation and the Metabolic Syndrome

Abstract

The present review, to the authors' knowledge, is the first to specifically address the relationships between microcirculation and metabolic syndrome, a cluster of metabolic and cardiovascular modifications highly prevalent in the general population. Its close link to overweight and insulin resistance makes it the main cause of the worldwide burden of type 2 diabetes. However, metabolic syndrome is also observed in many other diseases, particularly, but not exclusively, those where insulin resistance is a main feature. Analysis of the literature reveals that this clinical situation is invariably linked to microvascular disturbances, such as abnormalities in arteriolar reactivity, capillary recruitment, permeability, and hemorheology. A particularly interesting observation is that these defects in small vessel structure and function are seen very early in life or disease. Very importantly, they further suggest that microcirculatory abnormalities may be not only secondary but also causal to the development and/or aggravation of insulin resistance and metabolic syndrome. Mechanisms responsible for these modifications remain largely unknown, but insulin's vascular effects in the microvascular network, detailed in this review, are at least one example of such connections. The existing data point to a clear, at least bidirectional, relationship between microcirculation and metabolic syndrome. Additional studies should determine the level of reciprocal causality.

Macrovascular and microvascular dysfunction in the metabolic syndrome

“…A few culprits have been implicated in this association, with free fatty acids (FFAs) and adipokines, such as tumor necrosis factor-a, the most intensively studied. 30 Insulin resistance, resulting in increased release of FFAs into the portal circulation, particularly from visceral fat, is likely to play a role. Indeed, in lean women, increasing FFA impairs capillary recruitment.…”

Visceral Fat Accumulation is Associated with Oxidative Stress and Increased Matrix Metalloproteinase-9 Expression in Atherogenic Factor-overlapped Model Rats

“…There was also a signi cantly positive relationship between VisF / BW ratio and oxidative stress in all groups, with the underlying pathological conditions of hypertension and hyperlipidemia having a weak yet direct effect on this relationship. Systemic oxidative stress, measured by animals 29,30 . Another proposed cause relates to the abundant synthesis and secretion of angiotensinogen by adipose tissue 31,32 , especially visceral tissue 32,33 .…”

Microvascular dysfunction: a direct link among BMI, waist circumference and glucose homeostasis in young overweight/obese normoglycemic women?

“…Cellular defects in insulin signaling pathways 34 and microvascular and endothelial dysfunctions have been described and/or hypothesized as causes of IR. [12][13][14][15] Results from experimental and human studies have suggested that insulin-mediated changes in muscle perfusion can modulate insulin-mediated glucose uptake. 11,35 The action of insulin, also seen in the skin, 36 can favor insulin itself and glucose availability to cells.…”

“…11 Although not yet fully established in a clinical setting, endothelial and MDs, characterized by decreased responses to endothelial-derived relaxing factors (essentially, but not only, nitric oxide) and alterations of hemodynamic parameters such as the number of perfused capillaries and baseline red blood cell velocity, respectively, have been hypothesized as primary causes of IR. [12][13][14][15] In type 2 diabetes mellitus, MD has been well characterized in the coronary bed 16 and the skin, 17 but in the young uncomplicated OW/obese persons, the extent of microvascular damage, tested by a non-invasive method, namely, the nailfold videocapillaroscopy, and its interrelationship with clinical-anthropometrical-laboratorial parameters remains to be determined. In this investigation, we compared the skin microvascular function at rest and during post-occlusive reactive hyperemia (PORH) after a 1 min arterial occlusion of lean or OW/obese young sedentary non-smoking normoglycemic women and evaluated whether the observed alterations were related to cardiovascular risk factors, indirect markers of IR and glucose homeostasis.…”