The impact of metabolic syndrome on left ventricular myocardial performance.

BACKGROUND: Metabolic syndrome (MetS) is common and is associated with increased cardiovascular morbidity and mortality. Recent prospective studies suggested that MetS is associated with increased risk of heart failure. In the present cross-sectional study, we examined the association between left ventricular myocardial performance with MetS. MATERIALS AND METHODS: A total of 550 non-diabetic subjects, 275 without MetS and 275 with MetS, matched for gender, age and body mass index and free of clinically apparent macrovascular disease were studied. MetS was diagnosed using the NCEP-ATP III criteria. Left ventricular myocardial performance was assessed using the Tei index. RESULTS: Both men and women with MetS had higher values of the Tei index, indicating worse myocardial performance, in comparison with those without MetS (p < 0.001). Participants with a cluster of more components of the MetS had higher Tei index values than those with fewer components of the MetS. In addition, among normotensive subjects, those with MetS had significantly higher Tei index values than subjects without MetS. Multivariate linear regression analysis, after adjustment for age and body mass index, demonstrated that MetS status and from the individual components of the MetS, high fasting blood glucose levels, higher blood pressure, low high density lipoprotein levels and high waist circumference were associated with worse myocardial performance. CONCLUSION: MetS is associated with subclinical myocardial dysfunction in both men and women. Strategies to reduce the cardiovascular burden and the risk of heart failure associated with MetS should aim at prevention of the MetS and its related conditions.

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects.

OBJECTIVE: The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. METHODS: Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. RESULTS: In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. CONCLUSIONS: Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.

Differentiation in the short- and long-term effects of smoking on plasma total ghrelin concentrations between male nonsmokers and habitual smokers.

To explore the association between the anorexigenic effects of nicotine and the orexigenic properties of ghrelin, plasma total ghrelin levels were measured in nonsmokers and habitual smokers before and after short-term exposure to cigarette smoke. Thirty-one male smokers and 23 nonsmoking volunteers were matched for age and body mass index. After an overnight fast and abstinence from smoking, they all smoked 2 cigarettes consecutively (same brand, rate of inhalation, and duration of smoking). Total ghrelin concentrations were measured by radioimmunoassay before smoking (baseline), immediately afterward, and 30, 60, and 90 minutes after the second cigarette. Baseline ghrelin levels were not different between smokers and nonsmokers. Smoking did not have an immediate influence on ghrelin concentrations in smokers (analysis of variance for repeated measurements, P=0.74), whereas there was a progressive decline in nonsmokers, reaching statistical significance at 30 minutes (P=.04) and a nadir at 60 minutes (P=.04) after smoking. Moreover, the area under the curve for the changes of ghrelin over time after smoking was lower in nonsmokers than in smokers (-287.2+/-167.1 vs 29.2+/-125.3 ng.min/L, P=.03). In conclusion, fasting plasma total ghrelin concentrations are not different between male smokers and nonsmokers. Smoking does not provoke any short-term change in ghrelin levels in smokers, but induces a decline in nonsmokers. If the anorectic effect of smoking is ghrelin induced, this effect may be present only in people not habituated to smoke exposure. In habitual smokers, ghrelin suppression by short-term smoking could be blunted as a result of desensitization due to prolonged nicotine exposure.

Arterial stiffness is inversely related to plasma adiponectin levels in young normotensive patients with type 1 diabetes.

OBJECTIVE This study investigated the association between arterial stiffness and plasma adiponectin in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Participants were normotensive patients with type 1 diabetes who were up to age 40 years. Subjects on statins with macrovascular disease or overt nephropathy were excluded. Large artery stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV), whereas plasma adiponectin was measured by radioimmunoassay. RESULTS Data from 80 patients (age 27.1 ± 6.1 years, BMI 24.2 ± 3.1 kg/m(2), HbA(1c) 7.5 ± 1.6%, 39 men, adiponectin 13.9 ± 6.7 µg/mL, and PWV 5.6 ± 0.9 m/s) were analyzed. Log adiponectin inversely correlated with age-adjusted PWV (r = -0.291, P = 0.009) and waist circumference (r = -0.427, P < 0.001). In a fully adjusted model, age, expiration/inspiration index, and log adiponectin were independently associated with PWV, explaining 39.6% of its variance. CONCLUSIONS Arterial stiffness is inversely related to adiponectin concentration in young patients with type 1 diabetes without major complications.

Meal-induced thermogenesis and macronutrient oxidation in lean and obese women after consumption of carbohydrate-rich and fat-rich meals.

OBJECTIVE: To examine differences in meal-induced thermogenesis and macronutrient oxidation between lean and obese women after consumption of two different isocaloric meals, one rich in carbohydrate (CHO) and one rich in fat. METHODS: A total of 19 lean and 22 obese women were studied on two occasions, 1 wk apart. In one visit they consumed a CHO-rich meal and in the other visit a fat-rich meal. The two meals were isocaloric and were given in random order. Resting energy expenditure and macronutrient oxidation rates were measured and calculated in the fasting state and every hour for 3 h after meal consumption. RESULTS: Meal-induced thermogenesis was not different between lean and obese subjects after the CHO-rich (P = 0.89) or fat-rich (P = 0.32) meal, but it was significantly higher after the CHO-rich compared with the fat-rich meal in the lean and the obese individuals (P < 0.05). Protein oxidation rate increased slightly but significantly after the test meals in both groups (P < 0.01). Fat oxidation rate decreased after consumption of the CHO-rich meal (P < 0.001), whereas it increased after consumption of the fat-rich meal in both groups (P < 0.01). CHO oxidation rate increased in both groups after consumption of the CHO-rich meal (P < 0.001). Oxidation rates of protein, fat, and CHO during the experiment were not significantly different between lean and obese participants. CONCLUSION: Meal-induced thermogenesis and macronutrient oxidation rates were not significantly different between lean and obese women after consumption of a CHO-rich or a fat-rich meal.

Acute hyperhomocysteinaemia blunts endothelial dependent and endothelial independent vasodilatation in diabetic patients.

The aim of this study was to investigate the effects of acute, methionine-induced hyperhomocysteinaemia on endothelial function of skin microcirculation in diabetic compared with non-diabetic persons. Endothelial- and non-endothelial-dependent vasodilatation of the skin microcirculation were evaluated in 20 persons with type 2 diabetes (59.95+/-2.36 years old) and 24 age- and gender-matched controls using laser Doppler flowmetry, during fasting and four hours after 0.1 g/kg methionine-induced acute hyperhomocysteinaemia. Methionine loading caused a comparable increase of homocysteine in the two groups. Four hours after induction of acute hyperhomocysteinaemia, endothelial-dependent vasodilatation (acetylcholine effect) was lower in the diabetic patients compared with the controls ([mean+/-SEM] 8.09+/-1.18-fold increase in diabetic patients vs. 11.11+/-1.33-fold increase in controls, p=0.027). The same was observed for the endothelial-independent vasodilatation (sodium-nitroprusside effect, 7.55+/-0.80-fold increase in the diabetic patients vs. 12.19+/-1.26-fold increase in controls, p=0.008). Acute hyperhomocysteinaemia causes a decreased response of both endothelial-dependent and endothelial-independent vasodilatation of the skin microcirculation in diabetic compared with non-diabetic persons. These alterations might contribute to the vascular complications of hyperhomocysteinaemia in diabetes, and especially the microvascular ones.

Increased left ventricular arrhythmogenicity in metabolic syndrome and relationship with myocardial performance, risk factors for atherosclerosis, and low-grade inflammation.

Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors recently associated with left ventricular dysfunction. Limited data exist on the association between MetS and ventricular arrhythmogenicity. This study examined differences in ventricular arrhythmogenicity assessed by classic (QT interval) and newer (spatial QRS-T angle [spQRS-Ta]) electrocardiographic markers in subjects with and without MetS. A total of 306 subjects, 153 with and 153 without MetS, matched for sex and age were examined. The spQRS-Ta, which vectorcardiographically quantifies the deviation between the directions of ventricular depolarization and repolarization, was measured using a computer-based electrocardiograph. Left ventricular mass index and myocardial performance were evaluated echocardiographically. The spQRS-Ta was significantly higher in subjects with in comparison with those without MetS. Left ventricular mass index, QT interval, and its dispersion were not different between the 2 groups. Left ventricular myocardial performance was worse in subjects with MetS and was associated with higher values of the spQRS-Ta. Multivariate linear regression analysis demonstrated MetS status as the strongest predictor of ventricular arrhythmogenicity. Addition of the high-sensitivity C-reactive protein in the model increased the explained variance of the spQRS-Ta by 11%. In conclusion, ventricular arrhythmogenicity is present in MetS and is associated with myocardial dysfunction, risk factors for atherosclerosis, and low-grade inflammation. The independent association between the spQRS-Ta and MetS implies that the clustering of the metabolic disturbances has additional prognostic information than its individual components in terms of ventricular arrhythmogenicity and may explain in part the excess cardiovascular risk in subjects with MetS.

Eating slowly increases the postprandial response of the anorexigenic gut hormones, peptide YY and glucagon-like peptide-1.

CONTEXT: The rate at which people eat has been suggested to be positively associated with obesity, although appetite and related gut hormones have not been measured. The objective of the study was to determine whether eating the same meal at varying speeds elicits different postprandial gut peptide responses. DESIGN AND SETTING: This was a crossover study at a clinical research facility. STUDY PARTICIPANTS: Seventeen healthy adult male volunteers participated in the study. INTERVENTION: A test meal consisting of 300 ml ice cream (675 kcal) was consumed in random order on two different sessions by each subject: meal duration took either 5 or 30 min. MAIN OUTCOME MEASURES: The postprandial response of the orexigenic hormone ghrelin and the anorexigenic peptides peptide YY and glucagon-like peptide-1 over 210 min was assessed. Visual analog scales for the subjective feelings of hunger and fullness were completed throughout each session. RESULTS: Peptide YY area under the curve (AUC) was higher after the 30-min meal than after the 5-min meal (mean +/- sem AUC 5 min meal: 4133 +/- 324, AUC 30 min meal: 5250 +/- 330 pmol/liter . min, P = 0.004), as was glucagon-like peptide-1 AUC (mean +/- sem AUC 5 min meal: 6219 +/- 256, AUC 30 min meal: 8794 +/- 656 pmol/liter . min, P = 0.001). There was a trend for higher visual analog scale fullness ratings immediately after the end of the 30-min meal compared with immediately after the 5-min meal. There were no differences in ghrelin response. CONCLUSIONS: Eating at a physiologically moderate pace leads to a more pronounced anorexigenic gut peptide response than eating very fast.

Differential effects of two isoenergetic meals rich in saturated or monounsaturated fat on endothelial function in subjects with type 2 diabetes.

OBJECTIVE: To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD). RESULTS: FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 +/- 2.5% and decreased after the SAFA-rich meal by 16.7 +/- 6.0% (Delta = -11.5 +/- 6.4%; P = 0.008). CONCLUSIONS: Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.

Rapid development of an axillary mass in an adult: a case of cystic hygroma.

Cystic hygroma is a congenital anomaly of lymphatic origin, which mainly develops during childhood. Its development in adulthood, however, has been proposed to be related to several predisposing factors such as trauma, infection, tumor growth or iatrogenic stimuli. The development of cystic hygroma in the extremities of adults is extremely rare and moreover, its development in the axillary region has, to our knowledge, been reported only once in the literature. We describe an unusual case of a cystic hygroma which developed rapidly in the axillary region of a female patient in the absence of any predisposing factor. The diagnostic workup and the need for surgical excision of the mass to obtain an accurate, histologic diagnosis is presented.

Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone.

Thyroid hormone plays a critical role in energy homeostasis through mechanisms, which are not fully understood. In the present study, we investigated possible alterations of important energy regulators such as leptin, adiponectin, and ghrelin in relation to changes in thyroid hormones. Thyroid hormone (250 microg/kg) was administered in male Wistar rats for 2 weeks (THYR), while hypothyroidism (HYPO) was induced by propylthiouracil administration (0.05% in drinking water) for 3 weeks. Untreated animals served as controls (NORM). Leptin and adiponectin were measured in plasma by ELISA, while total ghrelin was measured with RIA. Body weight was significantly reduced both in THYR and HYPO rats, while food intake was significantly increased in THYR and decreased in HYPO. This response was associated with various changes in leptin, adiponectin, and ghrelin in plasma. In fact, in THYR rats, leptin levels (mean +/- SEM) were 240 +/- 55 pg/ml as compared to 819 +/- 70 pg/ml in untreated rats (P < 0.05), while no changes were observed in ghrelin and adiponectin. In HYPO rats, leptin levels were 1400 +/- 200 pg/ml vs. 819 +/- 70 pg/ml in untreated rats (P < 0.05), while ghrelin and adiponectin were significantly increased in HYPO rats as compared to untreated rats (P < 0.05). Furthermore, T(3) and T(4) levels were inversely correlated to leptin (P = 0.014), while ghrelin and adiponectin were inversely correlated to weight changes (P = 0.05 and P = 0.03, respectively). In conclusion, leptin seems mainly to be involved in the thyroid hormone effects on energy homeostasis. Ghrelin and adiponectin may serve a compensatory physiological role in hypothyroidism.

High postprandial triglyceridemia in patients with type 2 diabetes and microalbuminuria.

Microalbuminuria (MA) is an independent risk factor for atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Postprandial lipemia is also associated with excess cardiovascular risk. However, the association between MA and postprandial lipemia in diabetes has not been investigated. A total of 64 patients with T2DM, 30 with and 34 without MA, were examined. Plasma total triglycerides (TGs), triglycerides contained in chylomicrons (CM-TG), and TGs in CM-deficient plasma were measured at baseline and every 2 h for 6 h after a mixed meal. Postheparin LPL and HL activities were also determined. Plasma levels of apolipoprotein A-V (apoA-V), apoC-II, and apoC-III were measured in the fasting state and 2 h postprandially. Patients with MA had higher postprandial total TG levels than those without MA (P < 0.001); this increase been attributed mainly to CM-TG. LPL activity and fasting concentrations of the measured apolipoproteins were not different between the studied groups, whereas HL activity was higher in the patients with MA. ApoC-II and apoC-III levels did not change postprandially in either study group, whereas apoA-V increased more in the patients with MA. These data demonstrate for the first time that MA is characterized by increased postprandial lipemia in patients with T2DM and may explain in part the excess cardiovascular risk in these patients.