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CONTEXT: The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. OBJECTIVE: To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. INTERVENTIONS: Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat

In the forthcoming decades, the problem of baby boomer retirement will put pressure on the sustainability of social security systems in a large number of countries in the world. We refer to this phenomenon as a demographic wave problem and in this paper we propose an operating method, developed on the basis of a general principle, which allows us to manage the issues of sustainability and intergenerational equity that arise when the demographic wave disrupts the demographic, economic, and financial stability of a defined contribution pension system. This principle overcomes the classical juxtaposition between the two alternative schemes of financial management of a pension system, funded or pay-as-you-go. Indeed, our approach shows that only the unmanageable pay-as-you-go part of the pension system, namely the group of individuals of the demographic wave, needs to be fully funded and not the whole pension system as is argued in the existing literature.

Objective: To evaluate the effect of surgical menopause and estrogen replacement therapy on atrio–ventricular conduction and ventricular repolarization in women. Methods: In a prospective, randomized, double-blind, placebo-controlled clinical trial 50 women underwent hystero–salpingo–oophorectomy. Twenty-five women were treated with 50 μg/die of transdermal estradiol and the other 25 were treated with placebo patches. The duration of the treatment was 12 cycles. Before surgery and after 12 cycles of treatment, a standard electrocardiogram was performed to evaluate atrio–ventricular conduction time and cardiac repolarization time. Results: No significant variations in atrio–ventricuar conduction time and cardiac repolarization time were detected between the two groups at entry, nor was there any difference in both groups after 12 cycles of treatment with transdermal estradiol. Conclusions: Surgical menopause and estrogen replacement therapy do not modify atrio–ventricular conduction and ventricular repolarization in women.

Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes—particularly diabetic women with the proliferative retinopathy—were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, inPPARGgene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not.

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. We examined the hypothesis that circulating levels of IL-18 were elevated in obese women and would be reduced by weight loss. In a sample of 40 obese (body mass index, 36.4 ± 3.1 kg/m2) women we found that plasma IL-18 levels were higher than in 40 normal weight control women (P < 0.01) and were positively associated with body weight (r = 0.46; P < 0.01) and visceral fat (waist to hip ratio; r = 0.39; P < 0.01). Caloric restriction-induced weight loss (≥10% of original weight) over 1 yr reduced IL-18 levels from 247 (204/309) to 147 (111/210) pg/ml (medians and 25%/75%; P < 0.01), positively associated with changes in body mass index and waist to hip ratio. In obese women, IL-18 levels are associated with body weight and abdominal fat deposition; weight loss is an important intervention to reduce IL-18 levels. IL-18 may be a novel cytokine operating in human obesity.

We report the effects of a Mediterranean-style diet, with or without calorie restriction, on biomarkers of aging and oxidative stress in overweight men. 192 men were randomly assigned to either a Mediterranean-style diet or a conventional diet. The intervention program was based on implementation of a Mediterranean dietary pattern in the overweight group (MED diet group), associated with calorie restriction and increased physical activity in the obese group (lifestyle group). Both groups were compared with participants in two matched control groups (advice groups). After 2 years, there was a significant difference in weight loss between groups, which was −14 kg (95% CI −20 to −8) in lifestyle groups and −2.0 kg (−4.4 to 0) in the advice groups, with a difference of −11.9 kg (CI −19 to −4.7 kg, 𝑃 < . 0 0 1 ); moreover, there was a significant difference between groups at 2 years for insulin ( 𝑃 = . 0 4 ), 8-iso-PGF2α ( 𝑃 = . 0 3 7 ), glucose ( 𝑃 = . 0 4 ), and adiponectin ( 𝑃 = . 0 1 ). Prolonged adherence to a Mediterranean-style diet, with or without caloric restriction, in overweight or obese men is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress, and improved insulin sensitivity.

Aim: Endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are markers of endothelial injury and repair. We compared the effects of pioglitazone versus metformin on the circulating numbers of EMPs and EPCs in patients with newly diagnosed type 2 diabetes. Methods: This was a randomized, double-blind, comparator-controlled, 24-week single-centre trial conducted in a Teaching Hospital in Naples, Italy. One hundred and ten people with newly diagnosed type 2 diabetes who were never treated with antihyperglycaemic drugs and had haemoglobin A1c (HbA1c) levels between 7 and 10% were given pioglitazone hydrochloride (15–45 mg/day) (n = 55) or metformin (1000–2000 mg/day) (n = 55) as an active comparator. Absolute change from baseline to final visit in circulating EMPs and EPCs and their ratio were the main outcomes. Results: Baseline characteristics did not differ between the study groups. The decrease in circulating EMPs CD31+ [intergroup difference, −32 counts/µl (95% CI −51 to −9)] and the increase in EPCs CD34+/KDR+ [intergroup difference, 33 cells/106 events (95% CI 13 to 55)] were greater with pioglitazone versus metformin. EMPs/EPCs ratio was reduced with pioglitazone and unchanged with metformin [difference, −1.5 (95% CI −2.6 to −0.5), p < 0.001]. Participants assigned to pioglitazone gained more weight and experienced greater improvements in some coronary risk measures [high-density lipoprotein (HDL)-cholesterol, triglycerides, adiponectin and C-reactive protein (CRP)] than did those assigned to metformin. Conclusion: Compared with metformin, pioglitazone treatment improved the imbalance between endothelial damage and repair capacity and led to more favourable changes in coronary risk factors in patients with newly diagnosed type 2 diabetes.

Background and aims Obesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight. Methods and results Fifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P = 0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r = 0.35; P = 0.02) and visceral fat (waist–hip ratio; r = 0.32; P = 0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153) pg/ml (median and 25%/75%; P = 0.03), and it was positively associated with changes in body mass index and waist–hip ratio. Conclusion In premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist–hip ratio, and are reduced by weight loss.

Aims Mediterranean-type diets reduce the risk of Type 2 diabetes. Whether a Mediterranean-type diet improves glycaemic control in diabetes remains unknown. Methods Weconducted a cross-sectional analysis in 901 outpatientswith Type 2 diabetes attending diabetes clinics located in Campania County, South Italy. We explored the relation between glycated haemoglobin (HbA1c), measured centrally, selfmeasured pre- and postprandial glucose levels and consumption of a Mediterranean-type diet. Adherence to a Mediterraneantype diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0–9, with higher scores indicating greater adherence). The study was conducted from 2001 to 2007. Results Diabetic patients with the highest scores (6–9) had lower body mass index and waist circumferences, a lower prevalence of the metabolic syndrome and lower HbA1c and post-meal glucose levels than diabetic patients with the lowest scores (0–3). In multivariate analysis,meanHbA1c and 2-h post-meal glucose concentrations were significantly lower in diabetic patients with high adherence to a Mediterranean-type diet than those with low adherence [difference: HbA1c 0.9%, 95% confidence intervals (CI) 0.5–1.2%, P < 0.001; 2-h glucose 2.2 mmol ⁄ l, 95% CI 0.8–2.9 mmol⁄ l, P < 0.001]. Conclusions In Type 2 diabetes, greater adherence to a Mediterranean-type diet is associated with lower HbA1c and postprandial glucose levels. Diabet. Med. 26, 900–907 (2009) Keywords diet, glycaemic control, HbA1c, postprandial glucose, Type 2 diabetes Abbreviations BMI, body mass index; BMR, basal metabolic rate; CAPRI, Campanian Postprandial Hyperglycemia Study; HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; MUFA, monounsaturated fatty acid; WHR, waist– hip ratio

The role of dietary factors in erectile dysfunction (ED) has never been addressed. In the present case-control study, we investigated the relation of the Mediterranean diet with ED. A total of 100 men with ED were compared with 100 age-matched men without ED. A scale indicating the degree of adherence to the Mediterranean diet was constructed: the total Mediterranean diet score ranged from 0 (minimal adherence to the Mediterranean diet) to 9 (maximal adherence). The percentage of physical inactivity was greater in the ED group (35 vs 19%, P=0.04), whereas the diet score was lower (4.7+/-0.5 vs 5.4+/-0.5, P

Erectile and endothelial dysfunction may have some shared pathways through a defect in nitric oxide activity. We evaluated associations between erectile function, endothelial function and markers of systemic vascular inflammation in 80 obese men, aged 35-55 yr, divided into two equal groups according to the presence/absence of erectile dysfunction. Compared with non-obese age-matched men [no.=50, body mass index (BMI)=24 +/- 1], obese men (all) had impaired indices of endothelial function as suggested by the reduced mean blood pressure and platelet aggregation responses to L-arginine, and higher circulating concentrations of the proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), as well as C-reactive protein (CRP). The mean erectile function score was 14 +/- 4 (range 7-19) in obese men with erectile dysfunction and 23.5 +/- 1 (range 22-25) in obese men without erectile dysfunction. Endothelial function showed a greater impairment in impotent obese men as compared with potent obese men. The mean blood pressure and platelet aggregation decreases following L-arginine were -1.5 +/- 1.1 mmHg and -1.1 +/- 1.2%, respectively, in obese men with erectile dysfunction, and -3.4 +/- 1.2 mmHg and -5.6 +/- 2.1%, respectively, in obese men without erectile dysfunction (p < 0.01). Circulating CRP levels were significantly higher in obese men with erectile dysfunction as compared with obese men without erectile dysfunction (p < 0.05). Erectile function score was positively associated with mean blood pressure responses to L-arginine and negatively associated with BMI, waist-to-hip ratio (WHR), and CRR Erectile and endothelial dysfunction associate in obese men and may contribute to their raised cardiovascular risk through impaired nitric oxide availability elicited by a low-grade inflammatory state.

ContextThe metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood.ObjectiveTo assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome.Design, Setting, and PatientsRandomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III.InterventionsPatients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat

OBJECTIVE—Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss. RESEARCH DESIGN AND METHODS—Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women. RESULTS—Compared with nonobese women, obese women had increased concentrations of CRP (P < 0.01), TNF-α (P < 0.01), IL-6 (P < 0.01), and IL-18 (P < 0.01). Moreover, obese women had a higher myocardial performance index (P < 0.02) and lower transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02), and ejection fraction (P < 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-α, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P < 0.01) and CRP (P < 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity. CONCLUSIONS—In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women.

Background: A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines. Objective: We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus. Design: Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals. Results: Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals. Conclusions: This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.

It has been postulated that type 2 diabetes is a manifestation of the inflammatory host response (1). Increased inflammatory activity is believed to play a critical role in development of atherogenesis and to predispose established atherosclerotic plaques to rupture (2). Interleukin (IL)-8 is a potent chemoattractant (chemokine) and induces recruitment of neutrophils and T-cells into the subendothelial space, as well as adhesion of monocytes to endothelium (3). IL-18 is a potent proinflammatory cytokine reported to play a role in plaque destabilization and to predict cardiovascular death in patients with coronary artery disease (4). Adiponectin is an …

ContextObesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue.ObjectiveTo determine the effect of a program of changes in lifestyle designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance.Design and SettingRandomized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy.PatientsOne hundred twenty premenopausal obese women (body mass index ≥30) aged 20 to 46 years without diabetes, hypertension, or hyperlipidemia.InterventionsThe 60 women randomly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10% or more through a low-energy Mediterranean-style diet and increased physical activity. The control group (n = 60) was given general information about healthy food choices and exercise.Main Outcome MeasuresLipid and glucose intake; blood pressure; homeostatic model assessment of insulin sensitivity; and circulating levels of interleukin 6 (IL-6), interleukin 18 (IL-18), C-reactive protein (CRP), and adiponectin.ResultsAfter 2 years, women in the intervention group consumed more foods rich in complex carbohydrates (9% corrected difference; P

Patients with newly diagnosed type 2 diabetes are usually managed by pharmacotherapy as well as lifestyle changes. The latter are often ineffective and pharmacotherapy may fail over time or may increase cardiovascular and other risks. Specific diets recommended for weight loss in overweight and obese individuals with type 2 diabetes are low-carbohydrate and low-fat calorie-restricted diet. Mediterranean-style diets (MED) have been recommended because they increase insulin sensitivity and improve control of coronary risk factors and hyperglycemia. However, there have been few direct long-term comparisons with other diets in patients with diabetes. This single-center, randomized trial compared the long term effectiveness of a low-carbohydrate MED diet and a low-fat diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes. Effects on glycemic control and coronary risk factors were also compared. The study subjects were 215 overweight individuals, 30 to 70 years of age with newly diagnosed type 2 diabetes, who had a hemoglobin Alc (HbA 1c ) level