Components of the metabolic syndrome and carotid atherosclerosis: role of elevated blood pressure

Elevated blood pressure is among the factors that contribute to the metabolic syndrome (MetS). It is not known whether subjects with MetS and elevated blood pressure are at the same cardiovascular risk as subjects with MetS but without elevated blood pressure. To clarify this point, we have evaluated the prevalence of carotid atherosclerosis in subjects with MetS with or without elevated blood pressure. A large population was examined (842 women and 1011 men). Blood pressure, lipids, glucose, and waist were measured by routine methods. Carotid atherosclerosis was evaluated by echo Doppler examination. The prevalence of MetS was 24.4% in women and 28.7% in men. The prevalence of carotid atherosclerosis was 35.1% in women and 37.3% in men (p=NS), and increased with increasing number of MetS components. Age, smoking, and systolic blood pressure (SBP) were associated with the presence of carotid atherosclerosis (logistic model), whereas age, high-density lipoprotein cholesterol, and SBP were associated with the extent of atherosclerosis (linear model). When comparing subjects with an equal number of MetS components, the prevalence of carotid atherosclerosis was significantly higher in subjects with elevated blood pressure than in those without. No difference in carotid atherosclerosis prevalence was found in subjects bearing or not bearing components of the syndrome other than elevated blood pressure. The present findings demonstrate that subjects with MetS and elevated blood pressure have increased carotid atherosclerosis compared with subjects with MetS but without elevated blood pressure. The diagnosis of MetS per se might not adequately identify subjects at elevated cardiovascular risk.     

Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile

To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.     

Tissue-specific expression of two alternatively spliced isoforms of the human insulin receptor protein

Two insulin receptor mRNA species are expressed in human tissues as a result of alternative splicing of exon 11. This event is regulated in a tissue-specific manner. To date, there is little information about the relative abundance of the two receptor protein isoforms on the cell surface. The aim of the present investigation was to assess whether the tissue-specific expression of the two insulin receptor mRNA species is paralleled by a similar pattern of expression of the two receptor protein isoforms. To this end, we assessed the relative distribution of the two receptor variants in various human tissues at the mRNA and protein levels. A PCR-based technique was used to measure the relative abundance of the two mRNA species, and two immunological assays were used to measure the relative steady-state expression of the two receptor protein isoforms. The expression of the two insulin receptor protein isoforms followed the tissue-specific pattern of expression of the two mRNA species.     

One-Hour Postload Plasma Glucose Levels Are Associated with Kidney Dysfunction

Background and objectives: A cutoff of 155 mg/dl for 1-hour postload plasma glucose (1hPG) during the oral glucose tolerance test (OGTT) is able to identify patients who are at high risk for type 2 diabetes and vascular atherosclerosis. We aimed to examine whether individuals with 1hPG ≥155 mg/dl are also at increased risk for chronic kidney disease (CKD).Design, setting, participants, & measurements: Atherosclerosis risk factors, OGTT, and estimated GFR by Chronic Kidney Disease Epidemiology Collaboration equation were analyzed in 1075 white individuals without diabetes.Results: The area under the receiver operating characteristic curve for 1hPG was the highest (0.700) compared with the areas under the receiver operating characteristic curve of 0, 30-minute, and 2-hour glucose concentrations. Individuals with 1hPG ≥155 mg/dl had a worse cardiometabolic risk profile, exhibiting significantly higher body mass index, BP, triglycerides, and fasting insulin levels and lower HDL, IGF-1 levels, and insulin sensitivity, than individuals with 1hPG <155 mg/dl. Estimated GFR was significantly lower in individuals with 1hPG ≥155 mg/dl. In a logistic regression model adjusted for age and gender, individuals with 1hPG ≥155 mg/dl showed an increased risk for CKD compared with individuals with 1hPG <155 mg/dl. When the logistic regression analysis was restricted to individuals who had normal glucose tolerance, those with 1hPG ≥155 mg/dl showed a higher risk for CKD compared with individuals with 1hPG <155 mg/dl.Conclusions: These data suggest that a cutoff point of 155 mg/dl for the 1hPG during OGTT may be helpful in the identification of individuals who are at increased risk for CKD.It is well established that individuals with impaired glucose tolerance (IGT) are at increased risk for both type 2 diabetes and atherosclerotic cardiovascular disease (CVD) (1). Conversely, there is evidence that 30 to 40% of individuals who develop type 2 diabetes have normal glucose tolerance (NGT) at baseline (2), and a number of studies have suggested a significant risk for CVD even in individuals with NGT (3). Recently, it has been reported that a cutoff point of 155 mg/dl for the 1-hour postload plasma glucose (1hPG) during the oral glucose tolerance test (OGTT) is able to identify individuals who are at high risk for development of type 2 diabetes among individuals with NGT or IGT (4,5). Moreover, individuals with NGT and 1hPG ≥155 mg/dl exhibit early signs of vascular atherosclerosis (6). Renal dysfunction is a worldwide health problem as a consequence of its adverse outcomes, including cardiovascular events and all-cause mortality (7). A longitudinal study has shown that prediabetes is associated with increased risk for chronic kidney disease (CKD) (8). Whether individuals with a 1hPG ≥155 mg/dl are at increased risk for CKD is still undefined. Because treating underlying risk factors for CKD is the best approach to preventing or delaying its adverse outcomes and lifestyle intervention and pharmacologic treatment in high-risk individuals have consistently demonstrated their efficacy in reducing the incidence of type 2 diabetes (9–11) and its associated cardiovascular complications (11,12), it would be important to identify individuals with increased risk for these clinical outcomes.The aim of this study was to assess whether individuals without diabetes and with elevated 1hPG are at increased risk for CKD in a group of white individuals. Because current equations have limited precision and may underestimate measured GFR at higher values, we used the new equation recently developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), a research group established by the National Institute of Diabetes and Digestive and Kidney Diseases (13).     

Isobaric gasless laparoscopy versus minilaparotomy in uterine myomectomy: a randomized trial

Background Isobaric gasless laparoscopy and minilaparotomy have been used as more recent minimally invasive approaches to myomectomy. This randomized trial aimed to compare the surgical and immediate postoperative outcomes for myomectomy performed by isobaric gasless laparoscopy with those for minilaparotomy. Methods A total of 100 patients with symptomatic uterine myomas requiring myomectomy were randomly allocated to the gasless laparoscopy group or the minilaparotomy group. The randomization procedure was based on a computer-generated list. The primary outcome was a comparison of the discharge times between the two procedures. A power calculation verified that more than 26 patients for each group was necessary to detect a difference of more than 24 h in discharge time with an alpha error level of 5% and a beta error of 80%. Continuous outcome variables were analyzed using the Student’s t-test. Discrete variables were analyzed with the chi-square test or Fisher’s exact test. A p value less than 0.05 was considered statistically significant. Results The mean discharge time was longer for minilaparotomy than for gasless laparoscopy (98.4 ± 1.4 vs 52.8 ± 1.6 h; p < 0.001). Gasless laparoscopy resulted in shorter times for canalization (21.6 ± 1.1 vs 32 ± 1.3 h; p < 0.05) and surgery (79.5 ± 25.1 vs 103.5 ± 24.9 min; p < 0.001). The intraoperative blood loss was less with gasless laparoscopy (154.2 ± 1.2 vs 188.6 ± 1.3 ml; p < 0.001). No intraoperative complications occurred, and no case was returned to the theater in either group. No conversion to standard laparotomy was necessary. Conclusions Isobaric gasless laparoscopy and minilaparotomy can be suitable options for uterine myomectomy. Several surgical and immediate postoperative outcomes were significantly better in the gasless laparoscopy group than in the minilaparotomy group. However, further controlled prospective studies are required to confirm the results.     

IRS1 G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of ‘low-frequency–low-risk’ variants

Aims/hypothesis  The aim of the study was to determine the association between IRS1 G972R polymorphism and type 2 diabetes; published data concerning this association have been conflicting. To obtain further insight into this topic, we performed a meta-analysis of all available case–control studies. Methods  We performed a meta-analysis of 32 studies (12,076 cases and 11,285 controls). Results  The relatively infrequent R972 variant was not significantly associated with type 2 diabetes (OR 1.09, 95% CI 0.96–1.23, p = 0.184 under a dominant model). Some evidence of heterogeneity was observed across studies (p = 0.1). In the 14 studies (9,713 individuals) in which the mean age at type 2 diabetes diagnosis was available, this variable explained 52% of the heterogeneity (p = 0.03). When these studies were subdivided into tertiles of mean age at diagnosis, the OR for diabetes was 1.48 (95% CI 1.17–1.87), 1.22 (95% CI 0.97–1.53) and 0.88 (95% CI 0.68–1.13) in the youngest, intermediate and oldest tertile, respectively (p = 0.0022 for trend of ORs). Conclusions/interpretation  Our findings illustrate the difficulties of ascertaining the contribution of ‘low-frequency–low-risk’ variants to type 2 diabetes susceptibility. In the specific context of the R972 variant, ~200,000 study individuals would be needed to have 80% power to identify a 9% increase in diabetes risk at a genome-wide significance level. Under these circumstances, a strategy aimed at improving outcome definition and decreasing its heterogeneity may critically enhance our ability to detect genetic effects, thereby decreasing the required sample size. Our data suggest that focusing on early-onset diabetes, which is characterised by a stronger genetic background, may be part of such a strategy. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Role of endogenous androgens on carotid atherosclerosis in non-obese postmenopausal women

BackgroundRecent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal women.Methods and resultsWe consecutively enrolled 101 postmenopausal women aged 45–75 (mean age 57.4) years referred to our University hospital menopausal health-screening clinic. The subjects underwent a medical history, a physical examination and biochemical analysis. Extracranial carotid arteries were assessed by ultrasound. Fifty percent of our sample had carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively) (P = 0.02) were significantly correlated to carotid atherosclerosis. In non-obese subjects we found that participants in the third tertile had a significantly lower prevalence of carotid atherosclerosis (P = 0.02) compared to those in the first tertile of testosterone.ConclusionsThese results suggest a possible protective role of endogenous androgens at least on carotid atherosclerosis. Of course these preliminary results should be supported by prospective studies. Also the different role of these hormones on obese and non-obese subjects needs to be clarified.     

Endogenous testosterone and endothelial function in postmenopausal women

OBJECTIVE: It is well known that coronary heart disease incidence increases in women after menopause. This phenomenon was related to reduced levels of female sex hormones. Estrogen decline, however, is not the only hormonal change during the postmenopausal period and estrogen administration did not protect women from cardiovascular disease. Therefore, it is justified to explore other hormonal changes. The role of androgens is still controversial. The aim of the present study was to investigate the relationship between endogenous sex hormones and endothelial function, measuring the brachial artery flow-mediated dilation. METHODS AND RESULTS: Sixty postmenopausal women were consecutively enrolled and underwent a clinical and biochemical examination. Brachial artery flow-mediated dilation was also evaluated by ultrasound. After correction for confounding variables, testosterone was positively correlated to flow-mediated dilation (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow-mediated dilation smaller than that in the highest tertile (P=0.02). CONCLUSIONS: This result could suggest that the development of cardiovascular disease after menopause is due not only to estrogen decline but also to androgen decline. More studies are needed to evaluate the role of androgen replacement therapy on postmenopausal women with low level of this hormone.