Miryam Ciotola

Mediterranean diet, endothelial function and vascular inflammatory markers.

OBJECTIVES To discuss present knowledge about the relation between adipose tissue, inflammation and the Mediterranean-style diet. DESIGN Review of the literature and personal perspectives. SETTING AND RESULTS Recent studies indicate that adipose tissue is an endocrine organ producing numerous proteins, collectively referred to as adipokines, with broad biological activity, which play an important autocrine role in obesity-associated complications. Adipose tissue in general and visceral fat in particular are thought to be key regulators of inflammation which is heavily involved in the onset and development of atherothrombotic disease. Moreover, chronic inflammation may also represent a triggering factor in the origin of the metabolic syndrome and type 2 diabetes mellitus. An increased release of proinflammatory adipokines from the visceral adipose tissue, associated with a reduced secretion of anti-inflammatory adipokines and cytokines, could determine a low-grade chronic inflammatory state which might play a role in the future development of the metabolic syndrome, diabetes and atherosclerosis through both insulin resistance and endothelial dysfunction. Interventions aimed at decreasing weight loss and improving adherence to a Mediterranean-style diet in people with obesity or metabolic syndrome decrease the inflammatory milieu and ameliorate both insulin resistance and endothelial dysfunction. CONCLUSIONS Appropriate dietary patterns, as those associated with the eating model of Mediterranean-type diets, represent therapeutic strategies to reduce inflammation and the associated metabolic and cardiovascular risk.

Oxidative stress in the metabolic syndrome.

The metabolic syndrome represents a cluster of several risk factors for atherosclerosis that increases the risk of future cardiovascular events. In this study, we evaluated whether oxidative stress is increased in subjects with the metabolic syndrome. We studied 100 subjects (50 men and 50 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, and 50 (25 men and 25 women) matched subjects without the syndrome. Insulin sensitivity was assessed with the homeostasis model assessment (HOMA) methods; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine; oxidative stress was assessed by measuring the circulating levels of nitrotyrosine (NT), considered a good marker for the formation of endogenous peroxynitrite. Compared with control subjects, patients with the metabolic syndrome had greater waist circumference, higher HOMA and systolic pressure values, higher triglyceride and lower HDL-cholesterol levels. NT levels were higher (0.44±0.12 μmol/l, mean±SD) while FMD was lower [7.3 (4.4/9.6), median and interquartile range]in subjects with the metabolic syndrome as compared with control subjects [0.27±0.08 and 11.8 (8.6/14.9), respectively, p<0.001]. There was an increase in NT levels and HOMA score as the number of components of the metabolic syndrome increased. NT levels were associated with waist circumference (r=0.38, p=0.01), triglycerides (r=0.32, p<0.02), systolic blood pressure (r=0.21, p<0.05) and fasting glucose (r=0.24, p<0.05). The oxidative stress that accompanies the metabolic syndrome is associated with both insulin resistance and endothelial dysfunction, providing a connection which is highly deleterious for vascular functions.

Pioglitazone Reduces Endothelial Microparticles in the Metabolic Syndrome

Emerging evidence indicates that in patients without diabetes but with features of the metabolic syndrome, the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand pioglitazone exerts direct effects on inflammation and endothelial dysfunction which may be independent of amelioration of insulin resistance.1,2 In particular, in nondiabetic patients with low high density lipoprotein cholesterol (HDL-C) and the metabolic syndrome, a 12-week treatment with pioglitazone significantly raised HDL-C and favorably affected lipoprotein particle size, markers of inflammation, and adipokines without changes in triglycerides, low density lipoprotein cholesterol, or weight.1 Improvements in endothelial function and circulating markers of inflammation were also observed in nondiabetic subjects with hypercholesterolemia or hypertension receiving a 8-week treatment with pioglitazone.2 In this perspective, PPAR-γ …

Characterization of a novel polymorphism in PPARG regulatory region associated with type 2 diabetes and diabetic retinopathy in Italy.

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, in PPARG gene, 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.

Rosiglitazone Cools Down Inflammation in the Metabolic Syndrome

To the Editor: We read with interest the article by Samaha et al1 demonstrating a favorable effect of short-term rosiglitazone treatment on the inflammatory milieu in nondiabetic subjects with low high-density lipoprotein cholesterol and the metabolic syndrome. Almost simultaneously, the same group reported similar effects of pioglitazone in subjects with the metabolic syndrome.2 The proinflammatory state that accompanies the metabolic syndrome is associated with both insulin resistance and endothelial dysfunction, providing a connection between inflammation and metabolic processes which is highly deleterious for vascular functions.3 PPAR-γ agonists have displayed unique characteristics, in both animal and clinical studies, indicating that they have antiatherogenic properties.4 These compounds may have direct beneficial effects on cardiovascular risk independent of their hypoglycemic action.5 Two pilot studies with troglitazone6 and pioglitazone7 have shown reduced carotid intima-media thickness in patients with type 2 …