Relationship between Plasma Adiponectin Levels and Metabolic Risk Profiles in Taiwanese Children

Objective: Adiponectin, a novel adipokine with antiinflammatory and insulin‐sensitizing properties, has an important role in glucose metabolism and is negatively correlated with body fat amount in adults. The purpose of this study was to evaluate the association of plasma adiponectin level with metabolic risk profiles and insulin resistance status among Taiwanese children. Research Methods and Procedures: We enrolled 1248 children (608 boys and 640 girls) to ascertain their demographic, anthropometric, and cardiovascular risk factors distribution in Taipei. We measured plasma insulin, adiponectin, and leptin levels by radioimmunoassay (Linco Research Inc, St. Charles, MO). We calculated an insulin resistance index (IRI) using the Homeostasis Model Assessment model and also calculated an insulin resistance syndrome (IRS) summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure, serum triglyceride, high‐density lipoprotein‐cholesterol (HDL‐C) (inverse), and insulin levels. Results: In general, the boys had larger BMI, higher systolic blood pressure, serum total cholesterol, and triglyceride, and lower plasma leptin and adiponectin levels than girls. Plasma adiponectin levels were correlated negatively with BMI, leptin, insulin, IRI, and IRS summary score but positively correlated with HDL‐C in both boys and girls. In multivariate regression analyses, adiponectin was negatively associated with insulin (girls only), IRI (girls only), and IRS score, and positively associated with HDL‐C in both genders even after adjusting for age, BMI, plasma leptin level, and other potential confounders. Discussion: These data suggest that plasma adiponectin levels were negatively associated with metabolic risk profiles that may have played a protective role in the development of insulin resistance among Taiwanese school children.     

The ENPP1 K121Q polymorphism is not associated with type 2 diabetes and related metabolic traits in an Iranian population

The K121Q polymorphism of the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been variably associated with insulin resistance and type 2 diabetes (T2D) in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that the K121Q variant might be associated with T2D and related metabolic traits in this population. The K121Q genotypes were determined by PCR-restriction fragment length polymorphism in 377 normoglycemic controls and 155 T2D patients. T2D patients had significantly higher values for systolic and diastolic blood pressure, BMI, glucose, cholesterol, triglyceride, LDL, apoB, insulin, and HOMA-IR, and lower levels of HDL than the normoglycemic subjects. The frequency of the Q allele did not differ between T2D and normoglycemic subjects (OR 0.96, 95% CI 0.90-2.00, P?=?0.70). The Q allele frequency was 16.5% in T2D and 15.2% in normoglycemic subjects. The ENPP1 genotype (KQ?+?QQ) was not associated with the systolic and diastolic blood pressure, glucose, triglyceride, cholesterol, LDL-C and HDL-C, apo B, BMI, HOMA-IR, and insulin levels in both normoglycemic and T2D groups. Our results suggest that the ENPP1 121Q allele might not be associated with T2D and related metabolic traits among Iranian subjects.     

A pathophysiological approach to metabolic syndrome using factor analysis in an adult Romanian population

The aim of the study was to examine the role of insulin resistance in etiopathogenesis of metabolic syndrome in an adult Romanian population using exploratory factor analysis. We analyzed 228 non-diabetic subjects randomized in respect to the age and sex distribution of the general population. For each patient, age, sex, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), HDL-cholesterol (HDL), plasma triglycerides (TG), fasting plasma glucose (FPG) and fasting insulin were obtained. Factor analysis was performed using principal component analysis, with Varimax rotation of the major determinants of metabolic syndrome. Mean age was 48.9 +/- 12.7 years; 107 (46.9%) were men and 121 (53.1%) women. We found three major factors, which are correlated with metabolic syndrome and may explain its variance. Factor 1 comprises SBP and DBP in men and SBP, DBP and BMI in women. Factor 2 comprises BMI, HDL, TG and FPG in men and BMI, TG and FPG in women. Factor 3 comprises fasting insulin in men and fasting insulin, TG and HDL in women. The finding of more than one factor suggests that insulin resistance is not the only pathophysiological mechanism involved. These factors appear to work independently of each other in men, but they intersect in women, suggesting that the pathophysiology of metabolic syndrome may be different in women compared with men.     

Leptin and metabolic syndrome in obese and non-obese children.

Metabolic syndrome is characterized by a clustering of metabolic abnormalities: insulin resistance - hyperinsulinemia, dyslipidemia (high triglycerides and low HDL - cholesterol serum concentrations), impaired glucose tolerance and/or type 2 diabetes, and hypertension. The aim of this study was to analyse the role of different variables of metabolic syndrome, including leptin, in 74 non-obese children and 68 children with non-syndromal obesity. As metabolic syndrome variables, we have included body mass index, waist circumference, trunk-to-total skinfolds (%), systolic blood pressure, diastolic blood pressure, glucose, uric acid, fasting insulin, triglycerides and high-density lipoprotein-cholesterol (HDL-C). Factor analysis showed 4 factors in each group. In non-obese children, waist circumference, BMI, fasting insulin, triglycerides, trunk-to-total skinfolds (%), leptin and uric acid loaded positively on factor 1, and HDL-C loaded negatively on this factor; systolic and diastolic blood pressure had high positive loadings in factor 2; HDL-C and leptin showed positive loadings and triglycerides and uric acid, negative loadings in factor 3; and, finally, glucose and insulin showed positive loadings in factor 4. These four factors explained 72.16 % of the total variance in the non-obese group. In obese children, BMI, waist circumference, leptin, diastolic blood pressure and systolic blood pressure loaded positively on factor 1; diastolic blood pressure, trunk-to-total skinfolds (%), uric acid and systolic blood pressure showed high positive loadings in factor 2; fasting insulin, glucose and triglycerides showed positive loadings in factor 3; and, finally, triglycerides showed positive loadings and HDL-C negative loadings in factor 4. These four factors explained 74.18 % of the total variance in the obese group. Our results point to a different homeostatic control of metabolic syndrome characteristics in obese and non-obese children. Leptin seems to play a key underlying role in metabolic syndrome, especially in the obese group.     

Meta‐analysis on the G‐308A Tumor Necrosis Factor α Gene Variant and Phenotypes Associated with the Metabolic Syndrome

Objective: The G‐308A tumor necrosis factor (TNF) α gene variant has been associated with obesity, insulin resistance, and hypertension. We performed a systematical review of the literature by means of a meta‐analysis to assess the association of the G‐308A TNFα polymorphism with the components of the metabolic syndrome. Research Methods and Procedures: Studies were identified by searches of the literature for reports using the terms: diabetes, insulin resistance, hypertension, obesity or metabolic syndrome and TNF, variants or polymorphism or alleles, and Nco or ?308. From 824 reports, we included 31 observational studies, case control and cohort at baseline, which analyzed the association between the TNFα polymorphism and one or more components of the metabolic syndrome. A fixed effect model was used to pool data from individual studies. Results: Obesity [odds ratio, 1.23; 95% confidence interval (CI), 1.045 to 1.45; p = 0.013] in a total of 3562 individuals from eight homogeneous studies, systolic arterial blood pressure (standardized difference, 0.132; 95% CI, 0.016 to 0.25; p < 0.03) in a total of 1624 individuals from four homogeneous studies and plasma insulin levels (standardized difference, 0.095; 95% CI, 0.020 to 0.17; p = 0.013) in a total of 3720 subjects from 16 homogeneous studies were positively associated with the ?308A variant. Discussion: These results indicate that individuals who carried the ?308A TNFα gene variant are at 23% risk of developing obesity compared with controls and showed significantly higher systolic arterial blood pressure and plasma insulin levels, supporting the hypothesis that the TNFα gene is involved in the pathogenesis of the metabolic syndrome.     

Lipoprotein-associated PAF-acetylhydrolase activity in subjects with the metabolic syndrome

Plasma- and lipoprotein-associated activity of the platelet activating factor acetylhydrolase (PAF-acetylhydrolase, PAF-AH) plays an important role in inflammation and in atherosclerotic process, which are present in the metabolic syndrome (MS). Paraoxonase 1 (PON1) is an esterase associated with high-density lipoprotein (HDL) which contributes to the anti-atherogenic effects of this lipoprotein. We investigated the activities of both enzymes in 60 patients with MS and 110 age- and sex-matched subjects without it (non-MS group). Plasma PAF-AH activity was higher in the MS compared to the non-MS group, while HDL-PAF-AH and serum PON1 activities were lower in the MS compared to the non-MS group. Univariate regression analysis in the MS group showed that plasma PAF-AH activity was positively associated with systolic blood pressure, whereas HDL-PAF-AH activity was inversely associated with the homeostasis model assessments (HOMA) index. Both associations remained significant in the multivariate regression analysis, suggesting that insulin resistance and systolic hypertension are major determinants for the alterations in plasma and HDL-associated PAF-AH activity among those observed in MS patients.     

Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men.

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.     

Post-streptococcal antibodies are associated with metabolic syndrome in a population-based cohort

Background

Streptococcal infections are known to trigger autoimmune disorders, affecting millions worldwide. Recently, we found an association between post-streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an enzyme involved in insulin degradation and insulin resistance. This led us to evaluate associations between post-streptococcal antibodies and metabolic syndrome, as defined by the updated National Cholesterol Education Program definition, 2005.

Methods and Findings

Metabolic data (HDL, triglycerides, fasting glucose, blood pressure, waist circumference, BMI, smoking), post-streptococcal antibodies (anti-Streptolysin O (ASO) and anti-PDI), and C-reactive protein (CRP, as a general inflammatory marker), were assessed in 1156 participants of the Wisconsin Sleep Cohort Study. Anti-PDI antibodies were found in 308 participants (26.6%), ASO≥100 in 258 (22.3%), and 482 (41.7%) met diagnostic criteria for metabolic syndrome. Anti-PDI antibodies but not ASO were significantly associated with metabolic syndrome [n = 1156, OR 1.463 (95% CI 1.114, 1.920), p = 0.0062; adjusted for age, gender, education, smoking]. Importantly, the anti-PDI - metabolic syndrome association remained significant after adjusting for CRP and fasting insulin.

Conclusions

Post-streptococcal anti-PDI antibodies are associated with metabolic syndrome regardless of fasting insulin and CRP levels. Whereas these data are in line with a growing body of evidence linking infections, immunity and metabolism, additional studies are necessary to establish the post-streptococcal – metabolic syndrome association.     

Body Mass Index and the Prevalence of Hypertension and Dyslipidemia

Objective: To describe and evaluate relationships between body mass index (BMI) and blood pressure, cholesterol, high‐density lipoprotein‐cholesterol (HDL‐C), and hypertension and dyslipidemia. Research Methods and Procedures: A national survey of adults in the United States that included measurement of height, weight, blood pressure, and lipids (National Health and Nutrition Examination Survey III 1988–1994). Crude age‐adjusted, age‐specific means and proportions, and multivariate odds ratios that quantify the association between hypertension or dyslipidemia and BMI, controlling for race/ethnicity, education, and smoking habits are presented. Results: More than one‐half of the adult population is overweight (BMI of 25 to 29.9) or obese (BMI of ≥30). The prevalence of high blood pressure and mean levels of systolic and diastolic blood pressure increased as BMI increased at ages younger than 60 years. The prevalence of high blood cholesterol and mean levels of cholesterol were higher at BMI levels over 25 rather than below 25 but did not increase consistently with increasing BMI above 25. Rates of low HDL‐C increased and mean levels of HDL‐C decreased as levels of BMI increased. The associations of BMI with high blood pressure and abnormal lipids were statistically significant after controlling for age, race or ethnicity, education, and smoking; odds ratios were highest at ages 20 to 39 but most trends were apparent at older ages. Within BMI categories, hypertension was more prevalent and HDL‐C levels were higher in black than white or Mexican American men and women. Discussion: These data quantify the strong associations of BMI with hypertension and abnormal lipids. They are consistent with the national emphasis on prevention and control of overweight and obesity and indicate that blood pressure and cholesterol measurement and control are especially important for overweight and obese people.     

Prevalence of metabolic syndrome and gender differences

In a comparative study, involving 500 subjects with 294 males and 206 females aged 30 years and above, data were collected from NIMS (National Institute of Medical Sciences) hospital and research centre and controls from the general population whose age and sex were matched with subjects during the years 2010 - 2011. Metabolic syndrome was present both in women and men corresponding to 29% and 23% of the women's and men's sample, respectively. The prevalence was higher in women than in men. In women, elevated BMI, low HDL cholesterol, increased waist circumference and hyperglycemia were significantly larger contributors to the metabolic syndrome while in men these were hypertension and elevated triglycerides. The contribution of several metabolic components to the metabolic syndrome is different in men and women. This might contribute to gender specific differences in the relative risk of metabolic complications such as insulin resistance.     

Apolipoprotein B, apolipoprotein A-I, insulin resistance and the metabolic syndrome

PURPOSE OF REVIEW: The goal of identifying subjects with metabolic syndrome is to detect those at higher risk of developing cardiovascular disease. Evidence continues to accumulate as to the superiority of apolipoprotein B and apolipoprotein A-I over the conventional lipoprotein lipids as markers of vascular risk. It would seem reasonable, therefore, to redefine the dyslipidemia of the metabolic syndrome incorporating apolipoproteins. Therefore, our objective is to elucidate how apolipoprotein B and apolipoprotein A-I amplify evidence of the interactions amongst metabolic syndrome, insulin resistance, abdominal obesity, and vascular risk. RECENT FINDINGS: In several large epidemiological studies, including the NHANES III database, apolipoprotein B/apolipoprotein A-I ratio was tightly linked to the metabolic syndrome and each of its components, the descending order being: low HDL cholesterol, high triglyceride, high waist circumference, high glucose, and high blood pressure. Moreover, apolipoprotein B associates more closely with inflammatory markers and insulin resistance than triglyceride and all cholesterol markers. Yet despite close association of the apolipoprotein B/apolipoprotein A-I ratio to metabolic syndrome, both are independent predictors of future myocardial infarction. SUMMARY: We believe that the dyslipidemia of the metabolic syndrome should be redefined to include apolipoprotein B and apolipoprotein A-I.     

Estimation of the heritability of latent variables which are included in a structural model for metabolic syndrome

In a study looking for risk factors of atherosclerosis in families with combined hyperlipidemia and hypertension, clinical and biochemical data of 1,149 persons were analyzed to develop two hypothetical multivariate scores concerning the degree to which a patient is affected by the metabolic syndrome. The scores are based on a structural model for low-density cholesterol (LDL) and high-density cholesterol (HDL), triglycerides, uric acid, creatinine, glucose, insulin, systolic blood pressure and waist-to-hip ratio. Age, gender and body mass index were used for adjusting all variables. In segregation analyses of 42 pedigrees without using genotype information, estimations of the heritabilities and environmentally caused variance and covariance components were computed for the individual score values of the two latent factors. The first score shows a heritability of 42%; the environment component disappeared. The score mainly reflects the HDL, LDL and triglyceride levels. The second score shows a heritability of 16% with an environment component of 7%. It includes mainly insulin, uric acid and creatinine. In the search for genetic causes, both scores could be a basis for further phenotypic classification of the metabolic syndrome.     

Heritability of determinants of the metabolic syndrome among healthy Arabs of the Oman family study

The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high-density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment-insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2-hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven.     

Antihypertensive effects of vanadium compounds in hyperinsulinemic,hypertensive rats

Although considerable evidence lends credence to the association between insulin resistance, hyperinsulinemia and essential hypertension, the precise nature of this relationship remains unexplained. In the present investigation, we examined the proposition that these metabolic defects contribute causally to the development of high blood pressure. If these metabolic abnormalities were responsible for the development of hypertension, then drug interventions that improve these defects should also decrease high blood pressure. Since previous studies have demonstrated that vanadium compounds enhance insulin action and lower plasma insulin levels in nondiabetic rats, we examined the effects of these compounds on insulin sensitivity, plasma insulin concentration and blood pressure in two hyperinsulinemic models of experimental hypertension. The animal models studied were the genetically predisposed spontaneously hypertensive rat and the fructose-hypertensive rat, where hypertension is induced in normotensive rats by feeding them a high fructose diet. Vanadium compounds caused marked and sustained decreases in plasma insulin concentration and blood pressure in both the animal models studied. Furthermore, the effect of the drugs on blood pressure was reversed by restoring plasma insulin levels in the drug-treated rats to those observed in their untreated counterparts. These data suggest that either hyperinsulinemia contributes to the development of hypertension in both the spontaneously hypertensive and the fructose-hypertensive rats or that the underlying mechanism is closely related to the expression of both these disorders.     

Association of PARL rs3732581 genetic variant with insulin levels, metabolic syndrome and coronary artery disease

PARL (presenilin-associated rhomboid-like) is a mitochondrial protein involved in mitochondrial membrane remodelling, and maps to a quantitative trait locus (3q27) associated with metabolic traits. Recently the rs3732581 (Leu262Val) variant was found to be associated with increased levels of plasma insulin, a finding not replicated in a larger cohort. The aim of the current study was to investigate the associations between rs3732581 and levels of plasma insulin, metabolic syndrome (MetS) and its components, and cardiovascular disease. The CUPID population consisted of 556 subjects with angiographically proven CAD and the CUDAS cohort consisted of 1,109 randomly selected individuals from Perth, Western Australia. Samples were genotyped using mutation-specific PCR. No significant associations were observed between rs3732581 and levels of plasma insulin, glucose, BMI or MetS in either population. However, carriers of the minor allele had significantly lower mean intima-media thickness (IMT) [0.69 mm, 95% CI (0.69, 0.70 mm); P = 0.004], compared with major allele homozygotes [mean IMT = 0.71 mm, 95% CI (0.70, 0.72 mm)] in the CUDAS population. Further analysis using a recessive model showed homozygous carriers of the minor allele were predisposed to CAD [OR 1.55, 95% CI (1.11, 2.16); P = 0.01]. Despite the functional evidence for a role of PARL in regulating insulin levels, no association with rs3732581 was found in the current study. Additionally, there were no associations with glucose levels, BMI or MetS. There were significant effects of the variant on mean IMT and risk of CAD. A role for PARL in metabolic conditions cannot be excluded and more comprehensive genetic studies are warranted.     

Is Leptin Concentration Associated with the Insulin Resistance Syndrome in Nondiabetic Men?

HAFFNER, STEVEN M., LEENA MYKKÄNEN, DAVID L. RAINWATER, PAULI KARHAPÄÄ, AND MARKU LAAKSO. Is leptin concentration associated with the insulin resistance syndrome in nondiabetic men? Obes Res. Objective Insulin resistance has been strongly associated with cardiovascular risk. Recently, leptin, a hormone that regulates appetite, has been associated with both obesity and insulin resistance. However, the possible relation of leptin to the insulin resistance syndrome has been controversial. Research Methods and Procedures To explore this issue, we examined the relation of leptin to blood pressure, lipid levels, low density lipoprotein (LDL) size, and glucose levels in 87 normoglycemic men. Results Leptin levels were significantly correlated with body mass index (BMI) (r = 0.494), fasting insulin (r = 0.576), whole-body glucose disposal rate (GDR) (r = ?0.566), fasting glucose (r = 0.510), total triglycerides (r= 0.294), apolipoprotein B 0 = 0.223), systolic blood pressure (r= O.223), and LDL size (r = ?0.244). After adjustment for BMI and GDR, leptin levels remained significantly correlated with fasting insulin, fasting glucose, triglyceride, apolipoprotein B, and systolic blood pressure. Leptin levels were also correlated with the number of metabolic risk factors (dyslipidemia, systolic blood pressure, and fasting glucose). Discussion We conclude that leptin concentrations may be associated with several cardiovascular risk factors related to insulin resistance syndrome. These associations are only partly explained by leptin's relationship with BMI and GDR.     

Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, is one of the most common hormonal disorders among premenopausal women and is associated with infertility, obesity, and insulin resistance. Accumulating evidence suggests a role of the blood coagulation factor gene F13A1 in obesity (GeneBank ID: NM_000129.3). The aim of this study was to investigate the association of intronic allelic variants of the F13A1 gene with PCOS susceptibility and metabolic parameters in lean and obese PCOS women. In a case-control study, we determined an intronic F13A1 single nucleotide polymorphism (SNP) (dbSNP ID: rs7766109) in 585 PCOS and 171 control women and tested for PCOS susceptibility and associations with anthropometric, metabolic and hormonal parameters. Genotype frequencies of the F13A1 SNP rs7766109 were equivalent in PCOS and control women. In PCOS women, F13A1 gene variants were significantly associated with body mass index (BMI) (p=0.013), systolic blood pressure (p=0.042), insulin response (AUCins) (p=0.015), triglycerides (TG) (p=0.001), and high density lipoprotein cholesterol (HDL) (p=0.012). In the subgroup of obese PCOS women free androgen index (FAI), free testosterone and sex hormone binding globulin (SHBG) as well as glucose measurements showed a significantly different pattern across F13A1 gene variants (p=0.043; p=0.039 and p=0.013, respectively). We report for the first time an association of the F13A1 SNP rs7766109 with BMI, androgens, and insulin resistance in PCOS women. Further studies are needed to confirm our findings and to evaluate whether F13A1 is causally involved in the pathogenesis of PCOS related metabolic and hormonal disturbances.     

Dietary patterns,abdominal visceral adipose tissue,and cardiometabolic risk factors in African Americans: The Jackson heart study

Objective:

To examine the relative association of abdominal visceral adipose tissue (VAT) with cardiometabolic risk factors between African and European Americans.

Design and Methods:

We conducted a cross‐sectional study of 2035 African Americans from Jackson Heart Study (JHS) and 3170 European Americans from Framingham Heart Study (FHS) who underwent computed tomography assessment of VAT and subcutaneous adipose tissue (SAT). The FHS participants were weighted to match the age distribution of the JHS participants and the metabolic risk factors were examined by study groups in relation to VAT.

Results:

JHS participants had higher rates of obesity, hypertension, diabetes and metabolic syndrome than FHS participants (all p = 0.001). The associations were weaker in JHS women for VAT with blood pressure, triglycerides, HDL‐C, and total cholesterol (p_interaction = 0.03 to 0.001) than FHS women. In contrast, JHS men had stronger associations for VAT with high triglycerides, low HDL, and metabolic syndrome (all p_interaction = 0.001) compared to FHS men. Similar associations and gender patterns existed for SAT with most metabolic risk factors.

Conclusions:

The relative association between VAT and cardiometabolic risk factors is weaker in JHS women compared to FHS women, whereas stronger association with triglycerides and HDL were observed in JHS men.     

The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.     

Association Of Peripheral 5-Hydroxyindole-3-Acetic Acid,A Serotonin Derivative,with Metabolic Syndrome and Low-Grade Inflammation

Objective: The constellation of metabolic abnormalities seen in metabolic syndrome (MetS) has been linked to atherosclerosis and adverse cardiovascular outcomes due to heightened inflammation. Accumulating evidence suggests that peripheral 5-hydroxyindole-3-acetic acid (5-HIAA), the derivative end-product of serotonin (5-HT), might be involved in the pathogenesis of obesity, and abnormal lipid and glucose metabolism. We examined the association between serum 5-HIAA concentrations and MetS and also highly sensitive C-reactive protein (hsCRP).Methods: We assessed 180 healthy adults (110 males and 70 females) in a cross-sectional setting. Anthropometric indices and blood pressure were measured, as were laboratory parameters including fasting 5-HIAA concentrations. The associations between 5-HIAA and individual components of MetS, as well as MetS as a single entity, were investigated with bivariate correlation and logistic regression analyses.Results: Eighty-nine individuals (49.4%) were diagnosed with MetS. Significant correlations were found between 5-HIAA concentrations and age (r = 0.184), waist circumference (r = 0.415), high-density lipoprotein (HDL) cholesterol (r = -0.148), systolic blood pressure (r = 0.374), diastolic blood pressure (r = 0.355), homeostasis model assessment of insulin resistance (r = 0.201), and hsCRP (r = 0.453) were found (P<.05 in all tests). In logistic regression, 5-HIAA was significantly associated with 4 MetS components including central obesity, raised triglycerides, raised blood pressure, and raised fasting plasma glucose (FPG) (P<.05). Moreover, 5-HIAA was a predictor of MetS as a single entity, and the relationship persisted after adjusting for hsCRP (odds ratio [OR] = 4.41, 95% confidence interval [CI]: 2.58-7.67, P<.001).Conclusion: Elevated concentrations of 5-HIAA are seen in individuals with MetS. Increased 5-HIAA is also associated with hsCRP, a marker of chronic lowgrade inflammation underlying MetS.Abbreviations: BMI = body mass index CI = confidence interval FI = fasting insulin FPG = fasting plasma glucose HbA1c = glycated hemoglobin HDL = high-density lipoprotein 5-HIAA = 5-hydroxyindole-3-acetic acid 5-HT = 5-hydroxytryptamine HOMA-IR = homeostatic model assessment of insulin resistance hsCRP = highly sensitive C-reactive protein LDL = low-density lipoprotein MetS = metabolic syndrome OR = odds ratio