Skin microcirculatory dysfunction is already present in normoglycemic subjects with metabolic syndrome
Introduction
The current obesity epidemic implies that this disease is becoming an increasingly important risk factor for cardiovascular disease. Hyperinsulinemia and insulin resistance (IR) are common features of obesity in both human and experimental animals. Insulin resistance has been proposed as the metabolic basis of atherogenesis in subjects with metabolic syndrome (MS) based on the concept that reduced insulin sensitivity is the primary abnormality giving rise to dyslipidemia, hypertension, impaired glucose tolerance, or type 2 diabetes mellitus diabetes mellitus (T2DM). Metabolic syndrome, phenotypically associated with abdominal obesity, presents some or all of these features and ultimately increases cardiovascular risks [1]. Although not yet established, endothelial and microcirculatory dysfunctions (MDs), characterized by decreased responses to endothelial-derived relaxing factors (essentially nitric oxide) and alterations of hemodynamic parameters such as number of perfused capillaries and baseline red blood cell velocity (RBCV), respectively, are hypothesized as primary causes of IR in several vascular beds [2], [3].
In the microcirculation, the most purposeful functions of circulation occur: transport of nutrients to tissues and removal of cellular excreta. The small arterioles control the blood flow to each tissue area, and local conditions in the tissues themselves control the diameters of the arterioles in turn. Thus, each tissue in most instances controls its own blood flow in relation to its needs. Microvascular morphology and hemodynamics can be studied noninvasively in humans, without disturbing the quantities that are being examined, by nailfold videocapillaroscopy [4]. In T2DM, MD has been well characterized in the coronary bed [5] and in skin [6]; but to our knowledge, there are no data available on MS at the normoglycemic milieu.
There are accumulating evidences of a relationship between impaired glucose tolerance and renal and retinal injuries [7]. Retinopathy has been also associated with blood pressure, lipid concentration, and body mass index (BMI) [8], supporting the concept that not only hyperglycemia but also previous metabolic disturbances could impair the microcirculation.
The coexistence of MS on both diabetes mellitus types is considered as a risk indicator of microvascular complications in a recent metascreen [9], reinforcing the role of other risk factors, apart from hyperglycemia, for microcirculatory damage. If these assumptions were correct, microvascular disturbances would appear early on subjects with MS already during normoglycemia or would even exist at its onset. Our aim was to investigate if subjects with MS without any degree of glucose intolerance would already have MD, evaluated by morphologic and functional changes on nailfold capillaries at rest and after an ischemic period.
Section snippets
Subjects
Thirty-six obese subjects (10 men, 26 women) with MS were selected at the Cardiometabolic Clinic for outpatient care of the State University of Rio de Janeiro. After physical examination, they proceeded to 75-g oral anhydrous glucose tolerance test (fasting and 2 hours), lipid profile, and plasma insulin determinations after 10- to 12-hour fast. All subjects enrolled were first-degree relatives of persons with T2DM, had normal glucose tolerance test according to the American Diabetes
Results
Anthropometric, clinical, and laboratory data of investigated groups and their differences are described on Table 1. Although sex proportion was not the same on controls and subjects with MS (68.8% men and 72.2% women, respectively), no significant intragroup differences on microvasculatory parameters dependent on sex could be found. Several abnormalities were detected on skin microvascular morphology and function on subjects with MS compared with controls (Table 2), expressed by smaller AF,
Discussion
Microcirculatory dysfunction has been described in obesity [8], first-degree relatives of persons with T2DM [16], [17], hypertension [18], and diabetes mellitus [6] using different methods. Our study showed that normoglycemic subjects with MS, diagnosed by the National Cholesterol Education Program–Adult Treatment Panel III criteria, already have morphologic abnormalities and, more importantly, MD. Impairments on RBCV and FCD at baseline and on RBCVmax and TRBCVmax during PORH, recorded by
Acknowledgment
The authors wish to thank Nicolas Wiernesperger, Nivaldo Villela, Luciana Bahia, Fernando Sicuro, Priscila A. Maranhão, Waldicio Soares, and Rodrigo Torres for excellent technical assistance.
Grant support: National Research Council of Brazil and State of Rio de Janeiro Financing Agency for Research.
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