Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

Aims

We examined, in a country of the African region, i) the prevalence of the metabolic syndrome (MetS) according to three definitions (ATP, WHO and IDF); ii) the distribution of the MetS criteria; iii) the level of agreement between these three definitions and iv) we also examined these issues upon exclusion of people with diabetes.

Methods

We conducted an examination survey on a sample representative of the general population aged 25–64 years in the Seychelles (Indian Ocean, African region), attended by 1255 participants (participation rate of 80.3%).

Results

The prevalence of MetS increased markedly with age. According to the ATP, WHO and IDF definitions, the prevalence of MetS was, respectively, 24.0%, 25.0%, 25.1% in men and 32.2%, 24.6%, 35.4% in women. Approximately 80% of participants with diabetes also had MetS and the prevalence of MetS was approximately 7% lower upon exclusion of diabetic individuals. High blood pressure and adiposity were the criteria found most frequently among MetS holders irrespective of the MetS definitions. Among people with MetS based on any of the three definitions, 78% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions.

Conclusion

We identified a high prevalence of MetS in this population in epidemiological transition. The prevalence of MetS decreased by approximately 32% upon exclusion of persons with diabetes. Because of limited agreement between the MetS definitions, the fairly similar proportions of MetS based on any of the three MetS definitions classified, to a substantial extent, different subjects as having MetS.     

The impact of central obesity as a prerequisite for the diagnosis of metabolic syndrome

Objective: To compare the prevalence of metabolic syndrome (MS) defined according to the American Heart Association (AHA)/National Heart Lung and Blood Institute (NHLBI) and the International Diabetes Federation (IDF) and to determine the effect of the presence of central obesity on the phenotype (insulin resistance and other cardiovascular risk factors) associated with MS. Research Methods and Procedures: We studied 4723 Chinese, Malays, and Asian Indians living in Singapore. Each individual was categorized according to the five criteria for MS as defined by the AHA/NHLBI and the IDF. The population was categorized according to the presence of three or more criteria and then further subcategorized according to the presence or absence of central obesity. Characteristics of each group were compared using ANOVA and the χ² test. Results: MS was present in 20.2% (IDF) and 26.9% (AHA/NHLBI) of the population. Of the population, 6.7% exhibited three or more features of MS without central obesity. Use of the IDF definition, which requires central obesity, is associated with greater insulin resistance but similar levels of other cardiovascular disease risk factors than the use of the AHA/NHLBI definition, which does not require central obesity. Discussion: In this Southeast Asian population, the IDF and the AHA/NHLBI definitions of MS identify different segments of the MS population. The IDF definition may be more appropriate for the identification of those with insulin resistance and increased risk of type 2 diabetes. In contrast, the AHA/NHLBI definition may better identify those at increased risk of cardiovascular disease.     

All-cause and cardiovascular disease mortality increased with metabolic syndrome in Taiwanese

Objective: This study aimed to investigate the relationship between mortality and metabolic syndrome using the America Heart Association/National Heart Lung Blood Institute (AHA/NHLBI) and International Diabetes Federation (IDF) definitions in a Taiwanese cohort. Methods and Procedures: A total of 124,513 participants, aged 20–94 years, from four nationwide health centers in Taiwan were recruited from 1998 to 1999. Cox proportional hazard regression analyses were used to estimate the relative risks (RRs) for all‐cause and cardiovascular disease (CVD) mortality for those with metabolic syndrome compared to those without metabolic syndrome over 8 years of follow‐up. Results: The baseline prevalence of metabolic syndrome was 22.4% by the AHA/NHLBI and 13.9% by the IDF definition. A total of 2,762 deaths (527 CVD) occurred. Using the AHA/NHLBI definition, the RRs (95% confidence intervals) of all‐cause and CVD mortality were 1.21 (1.09–1.34) and 1.77 (1.40–2.24), respectively, in men and 1.30 (1.12–1.49) and 1.69 (1.19–2.42), respectively, in women. The association between metabolic syndrome and mortality was attenuated when using the IDF definition. Excluding subjects with diabetes or CVD at baseline, the RRs for CVD mortality still remained significant using the two definitions. Discussion: Metabolic syndrome, using either the AHA/NHLBI or IDF definitions, is a common disorder in Taiwanese adults and is similarly associated with an increase in all‐cause and CVD mortality as found in Western populations. Our study suggests that Asians with metabolic syndrome are also at higher risk for death.     

Comparisons of Different Metabolic Syndrome Definitions and Associations with Coronary Heart Disease,Stroke, and Peripheral Arterial Disease in a Rural Chinese Population

ObjectivesWe estimated the prevalence of metabolic syndrome (MetS) and compared associations of different MetS definitions with coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD) in a rural Chinese population.MethodsAmong 4,748 residents (2,145 men and 2,603 women) aged 30+ years in rural China from 2006 to 2007, the prevalence of MetS was estimated by using five different definitions: modified World Health Organization (WHO), Chinese Diabetes Society (CDS), the updated National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) for Asian-Americans, International Diabetes Federation (IDF), and Joint Interim Statement (JIS). Multivariable logistic regression analyses were implemented to estimate the association between MetS and the prevalence of CHD, stroke and PAD, respectively.ResultsPrevalence of MetS in men was 11.5% (WHO), 14.8% (CDS), 32.4% (NCEP-ATP III), 27.5% (IDF) and 39.7% (JIS) and in women was 15.7% (WHO), 20.7% (CDS), 54.2% (NCEP-ATP III), 51.5% (IDF) and 54.2% (JIS), respectively. Respective ORs (95% CI) for associating MetS with CHD in men were 1.79 (1.02-3.17), 1.25 (0.69-2.26), 1.61 (1.01-2.58), 1.84 (1.14-2.96), and 1.53 (0.96-2.43). Corresponding ORs (95% CI) for stroke in men were 2.18 (95% CI 1.20 to 3.97), 2.20 (95% CI 1.25 to 3.89), 1.71 (95% CI 1.02 to 2.84), 1.30 (95% CI 0.77 to 2.23), and 1.61 (95% CI 0.97 to 2.68), respectively. In women, CHD and stroke were significantly associated with MetS using all five definitions of MetS. In addition, PAD was associated with all five MetS definitions in men, but not in women. Only hyperglycemia and BMI were significantly associated with PAD in women.ConclusionsIn this rural Chinese population, the JIS, IDF and CDS criteria may not be more suitable than WHO and updated NCEP-ATPIII definitions for screening high-risk individuals and estimating the risk of CHD and stroke from MetS, especially in men.     

The metabolic syndrome and risk of cardiovascular disease and diabetes: experiences with the new diagnostic criteria from the International Diabetes Federation.

Since the publication of the International Diabetes Federation (IDF) consensus definition of the metabolic syndrome (MetS) in 2005, numerous studies have compared the new IDF MetS category with previous MetS definitions in its association with the prevalence of cardiovascular disease, and in its ability to predict vascular events and incident diabetes. The present review shows that the amount of cardiovascular risk conferred by the respective MetS definitions varies between populations; in most populations it is lower with the IDF MetS than with alternative MetS definitions. For incident diabetes, the number of existing studies appears too limited to draw definite conclusions. Like earlier definitions of the MetS, the IDF MetS is based on distinctive cutoff points for MetS stigmata, neglecting the fact that the risk factors are continuous and not categorical variables.     

High Prevalence of Diabetic Retinopathy in Diabetic Patients Concomitant with Metabolic Syndrome

Objective

To evaluate the relationship between metabolic syndrome (MetS) and the prevalence of diabetic retinopathy (DR).

Research Design and Methods

We conducted a case-controlled study, with data obtained from 2,551 Chinese participants between 18–79 years of age (representing a population of 1,660,500 in a district of Beijing). 74 cases of DR were found following data assessment by two 45° digital retinal images. Subjects without DR (NDR group) selected from the remaining 2,477 subjects were matched 1:1 to the DR group by HbA1c. MetS was defined by incorporating diagnostic criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF).

Results

There were no statistical differences between the DR group and NDR group in a number of biological or laboratory tests. However, the percentage of patients with DR increased vs. patients without DR with the number of MetS components from 1 to 5 (14.3% vs. 85.7%, 38.9% vs. 61.1%, 49.1% vs. 50.9%, 61.4% vs. 38.6% and 83.3% vs. 16.7%, respectively) (Pearson χ² = 9.938, P = 0.037). The trend to develop DR with MetS was significantly higher than that without MetS (NMetS) (χ² = 5.540, P = 0.019). MetS was an independent statistical indicator of the presence of DR after adjusting for age and sex [odds ratio (95% CI): 2.701(1.248–5.849), P = 0.012], which is still the case with an additional adjustment for WC, SBP, TC, HbA1c and duration of diabetes [odds ratio (95% CI): 2.948(1.134–7.664), P = 0.027].

Conclusion

DR is one of the diabetic microvascular complications. Apart from poor glycemic control, the concomitance of other metabolic factors can also influence DR. MetS, defined as a cluster of metabolic risk factors, is a strong and independent indicator of DR, even to the same extent as glycemic control.     

A comparative study of the prevalence of the metabolic syndrome and its components in type 2 diabetic patients in two Caribbean islands using the new International Diabetes Federation definition

BACKGROUND AND AIM: Tobago and Trinidad are two Caribbean islands with distinct genetic background and lifestyles; while Tobago is serene and a tourist centre, Trinidad is characterized by a hustling and bustling lifestyle. The study was aimed at determining and comparing the prevalence of the metabolic syndrome (MetS) and its critical components in type 2 diabetic patients using the new International Diabetes Federation (IDF) definition. METHODS: Four hundred and thirteen (166 Tobago, 247 Trinidad) type 2 diabetic patients visiting 10 lifestyle disease clinics were studied. Blood pressure, anthropometric parameters (height, weight, body mass index and waist circumference) and overnight fasting blood samples were taken. Plasma glucose and serum triglycerides, total cholesterol, LDL- and HDL-cholesterol, insulin, and adiponectin were determined. Insulin resistance (IR) was determined using the HOMA method. RESULTS: The patients in Tobago were significantly older than patients in Trinidad (p < 0.001) but the duration of diabetes (9.4 +/- 0.5 vs. 11.1 +/- 0.7 yr), medications, generalized (31.7 vs. 38.8%) and central (78.5 vs. 83.7%) obesity were similar (p > 0.05). In comparison with patients in Tobago, diabetic patients in Trinidad, irrespective of gender, had significantly higher prevalence of IDF critical components such as raised BP, raised triglycerides and reduced HDL-cholesterol (all, p < 0.001). Thus, while more patients in Trinidad were diagnosed with MetS based on three or four components, more patients in Tobago were diagnosed based on two components (p < 0.001). CONCLUSIONS: There were high prevalence rates of the components of the MetS in both the islands of Tobago and Trinidad. Quantitatively, the aggregation of the components is higher in patients in Trinidad, which constitute greater risk for adverse cardiovascular outcome. Controlling central obesity should be the target in preventing MetS in the two islands.     

Impaired lung function is associated with obesity and metabolic syndrome in adults

Objective: Impaired lung function is associated with obesity and insulin resistance. In this study, we investigated the relationship between metabolic syndrome and impaired lung function in adults. Research Methods and Procedures: A total of 46,514 subjects 20 years and over (21,669 men and 24,845 women, mean age = 37.3 ± 11.2 and 37.0 ± 11.3 years, respectively) were recruited from four nationwide MJ Health Screening Centers in Taiwan from 1998 to 2000. Metabolic syndrome was defined using the National Cholesterol Education Panel (NCEP) metabolic syndrome criteria or America Heart Association/National Heart Lung Blood Institute (AHA/NHLBI) criteria. The relationship between metabolic syndrome and lung function test was examined using multivariate logistic regression analysis. Results: The prevalence of impaired lung function was 11.1% in men and 14.0% in women. The prevalence of metabolic syndrome was 5.8% using NCEP criteria and 12.8% using AHA/NHLBI criteria. In multivariate logistic regression analysis with adjustment for age, gender, BMI, smoking, alcohol drinking, and physical activity, restrictive lung impairment was independently associated with increased risk of having metabolic syndrome (p < 0.01, odds ratios = 1.221 using NCEP criteria and 1.150 using AHA/NHLBI criteria). Discussion: Obesity and metabolic syndrome were associated with impaired lung function in adults in Taiwan. Our results imply that obesity and insulin resistance may be the common pathways underlying lung function impairment and metabolic syndrome. Moreover, lung function test may be applied as an additional evaluation for metabolic syndrome in a clinical setting.     

Development and validation of a risk score for hospitalization for heart failure in patients with Type 2 Diabetes Mellitus

Background

Aortic distensibility (AD) is a marker of the elastic properties of the aorta. Reduction of AD occurs early in subjects with type 2 diabetes mellitus (T2DM) and it is associated with subclinical generalized atherosclerosis. Metabolic syndrome (MetS) is common in subjects with T2DM and predicts cardiovascular morbidity and mortality. This study examined the potential relationship between MetS and AD in a cohort of subjects with T2DM.

Methods and results

A total of 210 subjects with T2DM were studied. MetS was diagnosed using the NCEP/ATP-III criteria. AD was assessed non-invasively by ultrasonography. The prevalence of MetS was 64.8%. AD was not significantly different between subjects with and without MetS (1.80 ± 0.54 vs. 1.84 ± 0.53 10^-6 dyn^-1 cm², p = 0.55). Univariate linear regression analysis showed that AD was associated positively with male sex (p = 0.02) as well as glomerular filtration rate (p < 0.001), and negatively with age (p = 0.04), history of hypertension (p = 0.001), as well as duration of diabetes (p < 0.001). After multivariate adjustment, AD was associated independently and significantly only with age (p = 0.02), duration of diabetes p < 0.001), and history of hypertension (p = 0.004); no significant relationship was found with MetS status, the sum of the components of the MetS or the individual components-besides hypertension-of the MetS.

Conclusion

In subjects with T2DM, MetS status per se is not associated with reduction of AD. In addition, it was shown that besides ageing, duration of glycemia was a strong predictor of AD. From the components of the MetS only hypertension was associated with reduction of the elastic properties of the aorta.     

Description and Prediction of the Development of Metabolic Syndrome: A Longitudinal Analysis Using a Markov Model Approach

Background

Delineating the natural history of metabolic syndrome (MetS) is prerequisite to prevention. This study aimed to build Markov models to simulate each component’s progress and to test the effect of different initial states on the development of MetS.

Methods

MetS was defined with revised AHA/NHLBI criteria. Each reversible multistate Markov chain consisted of 8 states (no component, five isolated component states, 2-component state, and MetS state). Yearly transition probabilities were calculated from a five-year population-based follow up studywhich enrolled 2,247 individuals with mean aged 32.4 years at study entry.

Results

In men, high BP or a 2-component state was most likely to initiate the progress of MetS. In women, abdominal obesity or low HDL were the most likely initiators. Metabolic components were likely to occur together. The development of MetS was an increasing monotonic function of time. MetS was estimated to develop within 15 years in 12.7% of young men with no component, and 2 components developed in 16.3%. MetS was estimated to develop in 10.6% of women with at the age of 47, and 2 components developed in 14.3%. MetS was estimated to develop in 24.6% of men and 27.6% of women with abdominal obesity, a rate higher than in individuals initiating with no component.

Conclusions

This modeling study allows estimation of the natural history of MetS. Men tended to develop this syndrome sooner than women did, i.e., before their fifth decade of life. Individuals with 1 or 2 components showed increased development of MetS.     

Impact of Age and Gender on the Prevalence and Prognostic Importance of the Metabolic Syndrome and Its Components in Europeans. The MORGAM Prospective Cohort Project

Objective

To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS).

Methods

Using 36 cohorts from the MORGAM-Project with baseline between 1982–1997, 69094 men and women aged 19–78 years, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5.

Results

The prevalence of MetS, according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P<0.0001); with a 5-fold increase in women from ages 19–39 years to 60–78 years (7.4%/7.6% to 35.4%/37.6% for IDF/NCEP-ATPIII) and a 2-fold increase in men (5.3%/10.5% to 11.5%/21.8%). Using multivariate-adjusted Cox regressions, the associations between MetS and all three CVD events were significant (P<0.0001). For IDF/NCEP-ATPIII in men and women, hazard ratio (HR) for CHD was 1.60/1.62 and 1.93/2.03, for CVD mortality 1.73/1.65 and 1.77/2.06, and for stroke 1.51/1.53 and 1.58/1.77. Whereas in men the HRs for CVD events were independent of age (MetS*age, P>0.05), in women the HRs for CHD declined with age (HRs 3.23/3.98 to 1.55/1.56; MetS*age, P = 0.01/P = 0.001 for IDF/NCEP-ATPIII) while the HRs for stroke tended to increase (HRs 1.31/1.25 to 1.55/1.83; MetS*age, P>0.05).

Conclusion

In Europeans, both age and gender influenced the prevalence of MetS and its prognostic significance. The present results emphasise the importance of being critical of MetS in its current form as a marker of CVD especially in women, and advocate for a redefinition of MetS taking into account age especially in women.     

Serum Adiponectin Confers Little Protection Against Diabetes and Hypertension in Turkish Men

We determined serum adiponectin's role as a biomarker of metabolic syndrome (MetS), type 2 diabetes (DM) and hypertension among Turkish adults who have a high prevalence of MetS. Individuals with measured serum adiponectin concentrations, constituting a random sample of Turkish adults, were studied cross‐sectionally. MetS was identified by criteria of the Adult Treatment Panel‐III modified for male abdominal obesity. Median age of 547 men and 652 women was 54 years. MetS was identified in 46%. Linear regression analysis among nine variables revealed homeostatic model assessment (HOMA) index in both sexes and C‐reactive protein (CRP) only in men as inversely associated covariates of adiponectin, and sex hormone‐binding globulin (SHBG) as positive covariate in women. Age‐adjusted sex‐specifically dichotomized high vs. low adiponectin levels were significantly associated with DM (odds ratio (OR) 0.55, P = 0.01) and hypertension (OR 0.64, P = 0.012) in women, but not in men. Further adjustment for smoking status and presence of high/low BMI did not alter this sex‐based relationship. As regards association with MetS, low adiponectin and high BMI interacted significantly in each sex. Yet adiponectin was associated only in men additively to the simultaneously adjusted five MetS components. We conclude that adiponectin concentrations, clearly linked to metabolic disorders, may diverge among sexes regarding protection against cardiometabolic risk through anti‐inflammatory or antioxidative function, Turkish men alone revealing significant dysfunction independent of obesity. This dysfunction may underlie also the association of adiponectin levels with MetS in men to be independent of the MetS components.     

Epidemiologic behavior of obesity in the Maracaibo City metabolic syndrome prevalence study

Introduction

Obesity is a worldwide public health issue. Since the epidemiological behaviour of this disease is not well established in our country, the purpose of this study was to determinate its prevalence in the Maracaibo City, Zulia State- Venezuela.

Materials and Methods

A cross-sectional study was undertaken using the data set from the Maracaibo City Metabolic Syndrome Prevalence Study. The sample consists of 2108 individuals from both genders and randomly selected: 1119 (53.09%) women and 989 (46.91%) men. The participants were interrogated for a complete clinical history and anthropometric measurements. To classify obesity, the WHO criteria for Body Mass Index (BMI), and Waist Circumference (WC) from the IDF/NHLBI/AHA/WHF/IAS/IASO-2009 (IDF-2009) and ATPIII statements were applied.

Results

For BMI, obesity had an overall prevalence of 33.3% (n = 701), and according to gender women had 32.4% (n = 363) and men had 34.2% (n = 338). Overweight had a prevalence of 34.8% (n = 733), Normal weight had 29.8% (n = 629), and Underweight had 2.1% (n = 45). Adding Obesity and Overweight results, the prevalence of elevated BMI (>25 Kg/m²) was 68.1%. Using the IDF-2009 WC''s cut-off, Obesity had 74.2% prevalence, compared to 51.7% using the ATPIII parameters.

Conclusions

These results show a high prevalence of abdominal obesity in our locality defined by the WHO, IDF-2009 and ATPIII criteria, which were not designed for Latin-American populations. We suggest further investigation to estimate the proper values according to ethnicity, genetic background and sociocultural aspects.     

Cross-Sectional Assessment of Nut Consumption and Obesity,Metabolic Syndrome and Other Cardiometabolic Risk Factors: The PREDIMED Study

Introduction

Prospective studies have consistently suggested that nut consumption is inversely related to fatal and non-fatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors.

Objective

To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk.

Materials and Methods

Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and IDF criteria. Diabetes and hypertension were assessed by clinical diagnosis and dyslipidemia (high triglycerides, low HDL-cholesterol, and hypercholesterolemia) by lipid analyses. Nut consumption was assessed using a validated food frequency questionnaire and categorized as <1, 1–3, and >3 servings/wk. Control of confounding was done with multivariate logistic regression.

Results

Compared to participants consuming <1 serving/wk of nuts, those consuming >3 servings/wk had lower adjusted odds ratios (OR) for obesity (0.61, 95% confidence interval 0.54 to 0.68; P-trend <0.001), MetS (0.74, 0.65 to 0.85; P-trend<0.001), and diabetes (0.87, 0.78 to 0.99; P-trend = 0.043). Higher nut consumption was also associated with lower risk of the abdominal obesity MetS criterion (OR 0.68, 0.60 to 0.79; P-trend<0.001). No significant associations were observed for the MetS components high blood pressure, dyslipidemia, or elevated fasting glucose.

Conclusions

Nut consumption was inversely associated with the prevalence of general obesity, central obesity, MetS, and diabetes in subjects at high cardiovascular risk.     

Impact of Metabolic Syndrome on the Prognosis of Ischemic Stroke Secondary to Symptomatic Intracranial Atherosclerosis in Chinese Patients

Objectives

To analyze the effect of metabolic syndrome (MetS) on prognosis of ischemic stroke secondary to intracranial stenosis in Chinese patients.

Methods

A prospective cohort of 701 patients with ischemic stroke, caused by intracranial stenosis, were followed at 3-month intervals for 1 year to monitor development of recurrent stroke or death. Imaging was performed using magnetic resonance angiography. MetS was defined using International Diabetes Federation (IDF) criteria.

Results

MetS was identified in 26.0% of the cohort of stroke patients. Patients with MetS were more likely to be female, nonsmokers, and more likely to have a prior history of diabetes mellitus, high blood glucose and a family history of stroke than patients without MetS. During 1-year follow-up, patients with MetS had a non-significantly higher rate of stroke recurrence (7.1%) than patients without MetS (3.9%; P = 0.07). There was no difference in mortality (3.3% versus 3.5%, respectively). Multivariate Cox proportional hazards analysis (adjusting for gender, BMI, smoking, diabetes, and LDL-C) identified an association between that 1-year stroke recurrence and the presence of MetS (hazard ratio 2.30; 95% CI: 1.01–5.22) and large waist circumference (hazard ratio: 2.39; 95% CI: 1.05–5.42). However, multivariable analysis adjusting for the individual components of MetS found no significant associations between MetS and stroke recurrence. There were no associations between these parameters and mortality.

Conclusions

Chinese patients with symptomatic intracranial atherosclerosis who have MetS, are at higher risk of recurrent stroke than those without MetS. However, MetS was not predictive of stroke recurrence beyond its individual components and one-year mortality.     

Long-Term Exposure to Ambient Air Pollution and Metabolic Syndrome in Adults

Air pollutants (AP) play a role in subclinical inflammation, and are associated with cardiovascular morbidity and mortality. Metabolic syndrome (MetS) is inflammatory and precedes cardiovascular morbidity and type 2 diabetes. Thus, a positive association between AP and MetS may be hypothesized. We explored this association, (taking into account, pathway-specific MetS definitions), and its potential modifiers in Swiss adults. We studied 3769 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, reporting at least four-hour fasting time before venepuncture. AP exposures were 10-year mean residential PM₁₀ (particulate matter <10μm in diameter) and NO₂ (nitrogen dioxide). Outcomes included MetS defined by World Health Organization (MetS-W), International Diabetes Federation (MetS-I) and Adult Treatment Panel-III (MetS-A) using four- and eight-hour fasting time limits. We also explored associations with individual components of MetS. We applied mixed logistic regression models to explore these associations. The prevalence of MetS-W, MetS-I and MetS-A were 10%, 22% and 18% respectively. Odds of MetS-W, MetS-I and MetS-A increased by 72% (51-102%), 31% (11-54%) and 18% (4-34%) per 10μg/m³ increase in 10-year mean PM₁₀. We observed weaker associations with NO₂. Associations were stronger among physically-active, ever-smokers and non-diabetic participants especially with PM₁₀ (p<0.05). Associations remained robust across various sensitivity analyses including ten imputations of missing observations and exclusion of diabetes cases. The observed associations between AP exposure and MetS were sensitive to MetS definitions. Regarding the MetS components, we observed strongest associations with impaired fasting glycemia, and positive but weaker associations with hypertension and waist-circumference-based obesity. Cardio-metabolic effects of AP may be majorly driven by impairment of glucose homeostasis, and to a less-strong extent, visceral adiposity. Well-designed prospective studies are needed to confirm these findings.     

Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4 are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.