PURPOSE: Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS: Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF) and vascular resistance (VR) responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach) and independent (sodium nitroprusside-SNP) vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS: PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION: Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.

OBJECTIVE -Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The study included 31 subjects (age 38.3 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n ϭ 15) or metformin (n ϭ 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.RESULTS -The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.CONCLUSIONS -We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

OBJECTIVE -Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The study included 31 subjects (age 38.3 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n ϭ 15) or metformin (n ϭ 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.RESULTS -The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.CONCLUSIONS -We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

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Gynoid lipodystrophy, also known as cellulite, is a common multifactorial entity that affects millions of women around the world. There have been few scientific articles dealing with its physiology and treatment in the past few years, and vascular changes seem to play an important role in its pathophysiology. Skin microvascular alterations can be observed noninvasively with a new method called orthogonal polarization spectral imaging, which was used to evaluate the effectiveness of an anticellulite drug composed mainly of a 7% caffeine solution. Microcirculatory parameters evaluated were functional capillary density (FCD; number of flowing capillaries per unit area), diameter of the dermic papilla (DPD), and capillary diameter (CD). The clinical parameters analyzed were centimetrical measurements of thighs and hips and the influence of tobacco, alcohol, and physical activities on the efficacy of the treatment. After 1 month of treatment, statistical application of chi-squared and Z approximation tests showed, in treated patients, statistically significant reduction of thigh circumferences in more than 80% of the cases and reduction of hip circumference in 67.7%. FCD, DPD, and CD did not change significantly after treatment. Smoking as well as alcohol consumption and regular physical activity were not significantly related to the centimetrical reduction observed in treated thighs and hips.