Associations of amylin with inflammatory markers and metabolic syndrome in apparently healthy Chinese

Background

Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS) and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese.

Methods

A population-based sample of 1,011 Chinese men and women aged 35–54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6]), insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.

Results

Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001) without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001). After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46) comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR.

Conclusions

Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively.     

Familial aggregation of metabolic syndrome and its components in a large Chinese population

Objective: To investigate the familial aggregation of metabolic syndrome (MetS) and its components in the Chinese. Methods and Procedures: A total of 17,954 subjects from 5,224 families with multiple siblings aged 25–64 years old (mean age 45.8 years, 51.6% male) were enrolled from a rural area of Anhui Province of China during 2004–2005. Anthropometric measurement, body composition, blood pressure, plasma lipids, and fasting glucose and insulin, as well as a questionnaire interview, were obtained from each participant. Results: Significant correlations among siblings were observed in all the traits examined, including BMI, waist circumference, total body and abdominal fat percentage, fasting plasma glucose (FPG) and insulin, insulin resistance index of homeostatic model assessment (HOMA‐IR), total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol, and blood pressure, after adjustment for age, gender and some other covariates. The correlation coefficients varied from 0.18 for FPG to 0.42 for HDL‐C. In stratified analyses, we found siblings with a smaller age gap among them had higher intraclass correlation coefficients (ICCs) for most of the above phenotypes than those with a greater age difference, and the correlation of systolic blood pressure (SBP) was stronger in male siblings than that in female. If the eldest sibling is affected by MetS or any of its components, younger siblings bear a twofold to threefold higher risk for developing MetS or any of its components than those with a healthy eldest sibling. Discussion: Our study demonstrated a significant familial resemblance as regards MetS and its components among the Chinese. Further studies are warranted to investigate specific genetic and environmental factors related to MetS in this population.     

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged > or = 25 years) in three cohorts: AusDiab 2000-2005 (n = 5,039), Mauritius 1987-1992 (n = 2,849), and Mauritius 1987-1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P < 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987-1992, and four of six in Mauritius 1987-1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.     

Genotype by Energy Expenditure Interaction with Metabolic Syndrome Traits: The Portuguese Healthy Family Study

Moderate-to-high levels of physical activity are established as preventive factors in metabolic syndrome development. However, there is variability in the phenotypic expression of metabolic syndrome under distinct physical activity conditions. In the present study we applied a Genotype X Environment interaction method to examine the presence of GxEE interaction in the phenotypic expression of metabolic syndrome. A total of 958 subjects, from 294 families of The Portuguese Healthy Family study, were included in the analysis. Total daily energy expenditure was assessed using a 3 day physical activity diary. Six metabolic syndrome related traits, including waist circumference, systolic blood pressure, glucose, HDL cholesterol, total cholesterol and triglycerides, were measured and adjusted for age and sex. GxEE examination was performed on SOLAR 4.3.1. All metabolic syndrome indicators were significantly heritable. The GxEE interaction model fitted the data better than the polygenic model (p<0.001) for waist circumference, systolic blood pressure, glucose, total cholesterol and triglycerides. For waist circumference, glucose, total cholesterol and triglycerides, the significant GxEE interaction was due to rejection of the variance homogeneity hypothesis. For waist circumference and glucose, GxEE was also significant by the rejection of the genetic correlation hypothesis. The results showed that metabolic syndrome traits expression is significantly influenced by the interaction established between total daily energy expenditure and genotypes. Physical activity may be considered an environmental variable that promotes metabolic differences between individuals that are distinctively active.     

The 60- and 70-kDa heat-shock proteins and their correlation with cardiovascular risk factors in postmenopausal women with metabolic syndrome

We investigated the association between circulating levels of 60 and 70 kDa heat-shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal women with or without metabolic syndrome (MetS). This cross-sectional study included 311 Brazilian women (age ≥45 years with amenorrhea ≥12 months). Women showing three or more of the following diagnostic criteria were diagnosed with MetS: waist circumference (WC) ≥88 cm, blood pressure ≥130/85 mmHg, triglycerides ≥150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose ≥100 mg/dl. Clinical, anthropometric, and biochemical parameters were collected. HSP60, HSP70, antibodies to HSP60 and HSP70, and C-reactive protein (CRP) levels were measured in serum. Student''s t test, Kruskal–Wallis test, chi-square test, and Pearson correlation were used for statistical analysis. Of the 311 women, 30.9 % (96/311) were diagnosed with MetS. These women were, on average, obese with abdominal fat deposition and had lower HDL values as well as higher triglycerides and glucose levels. Homeostasis model assessment-insulin resistant (HOMA-IR) test values in these women were compatible with insulin resistance (P < 0.05). CRP and HSP60 concentrations were higher in women with MetS than in women without MetS (P < 0.05). HSP60, anti-HSP70, and CRP concentrations increased with the number of features indicative of MetS (P < 0.05). There was a significant positive correlation between anti-HSP70 and WC, blood pressure and HOMA-IR, and between CRP and WC, blood pressure, glucose, HOMA-IR, and triglycerides (P < 0.05). In postmenopausal women, serum HSP60 and anti-HSP70 concentrations increased with accumulating features of the metabolic syndrome. These results suggest a greater immune activation that is associated with cardiovascular risk in postmenopausal women with metabolic syndrome.     

Low-Density Lipoprotein Electronegativity Is a Novel Cardiometabolic Risk Factor

Background

Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction–L5–is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD.

Methods

In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score.

Results

L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference.

Conclusion

Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index.     

Associations of Body Composition Measurements with Serum Lipid,Glucose and Insulin Profile: A Chinese Twin Study

Objectives

To quantitate and compare the associations of various body composition measurements with serum metabolites and to what degree genetic or environmental factors affect obesity-metabolite relation.

Methods

Body mass index (BMI), waist circumference (WC), lean body mass (LBM), percent body fat (PBF), fasting serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), glucose, insulin and lifestyle factors were assessed in 903 twins from Chinese National Twin Registry (CNTR). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting serum glucose and insulin. Linear regression models and bivariate structural equation models were used to examine the relation of various body composition measurements with serum metabolite levels and genetic/environmental influences on these associations, respectively.

Results

At individual level, adiposity measurements (BMI, WC and PBF) showed significant associations with serum metabolite concentrations in both sexes and the associations still existed in male twins when using within-MZ twin pair comparison analyses. Associations of BMI with TG, insulin and HOMA-IR were significantly stronger in male twins compared to female twins (BMI-by-sex interaction p = 0.043, 0.020 and 0.019, respectively). Comparison of various adiposity measurements with levels of serum metabolites revealed that WC explained the largest fraction of variance in serum LDL-C, TG, TC and glucose concentrations while BMI performed best in explaining variance in serum HDL-C, insulin and HOMA-IR levels. Of these phenotypic correlations, 64–81% were attributed to genetic factors, whereas 19–36% were attributed to unique environmental factors.

Conclusions

We observed different associations between adiposity and serum metabolite profile and demonstrated that WC and BMI explained the largest fraction of variance in serum lipid profile and insulin resistance, respectively. To a large degree, shared genetic factors contributed to these associations with the remaining explained by twin-specific environmental factors.     

Relationship between adiponectin and metabolic variables in Caribbean offspring of patients with type 2 diabetes mellitus.

AIM: To examine the relationship between adiponectin and metabolic variables in the offspring of patients with type 2 diabetes mellitus. METHODS: Fasting blood samples and anthropometric indices were taken from 34 subjects, offspring of patients with type 2 diabetes, and 24 healthy control subjects without any immediate family history of diabetes. Plasma glucose and serum adiponectin, insulin, triglycerides, total cholesterol, HDL and LDL cholesterol levels were measured, and insulin resistance (IR) was calculated based on the homeostasis model assessment (HOMA) method. RESULTS: Offspring and control subjects were sex-matched, but the offspring were older and had higher body mass index and waist circumference than the control subjects (p < 0.05). The offspring had significantly higher mean fasting plasma glucose concentrations; however, their mean serum insulin, adiponectin, triglyceride, total cholesterol, HDL and LDL cholesterol and HOMA-derived IR levels did not significantly differ from those of the control subjects (p > 0.05). While the negative correlation between serum adiponectin and HDL cholesterol levels in the offspring remained statistically significant after adjusting for the effect of age, sex and BMI (r = -0.37, p < 0.05), the negative correlation between adiponectin and serum triglyceride, LDL cholesterol or IR levels became non-significant after controlling for the above variables (p > 0.05 in all cases). CONCLUSION: The correlation between adiponectin and some known biochemical risk factors for developing diabetes and cardiovascular disease in the offspring of patients with diabetes warrants further study to evaluate its potential in assessing the risk of developing these disorders.     

Genetic and Environmental Contributions to Phenotypic Components of Metabolic Syndrome: A Population‐based Twin Study

The increasing prevalence of metabolic syndrome (MS) poses a serious public‐health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their intercorrelations: waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TGs), and high‐density lipoprotein–cholesterol (HDL‐C). We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% confidence interval (CI): 0.00–0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL‐C, and FPG. HDL‐C was mainly influenced by common environmental factors (0.62, 95% CI: 0.58–0.62), whereas the other five MS components were largely influenced by unique environmental factors (0.32–0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as intercorrelated traits, and to carefully consider environmental and genetic factors in studying MS etiology.     

Association of Serum Irisin with Metabolic Syndrome in Obese Chinese Adults

Irisin, a recently identified novel myokine, drives brown-fat-like conversion of white adipose tissues and has been proposed to mediate beneficial effects of exercise on metabolism. Circulating irisin was significantly reduced in type 2 diabetes patients; however, no evidence is available about its association with metabolic syndrome (MetS) and effects of adiposity and muscle mass on circulating irisin have been controversial. Cross-sectional data on socio-demographic, lifestyle, clinical characteristics and serum irisin were collected for 1,115 community-living Chinese adults with central obesity. Associations of serum irisin with MetS (central obesity plus any two of the following four factors (raised blood pressure (BP), raised fasting plasma glucose (FPG), raised triglyceride (TG), and reduced HDL cholesterol) and each component of MetS were analyzed using multivariable logistic regression. Among the 1,115 obese Chinese adults with a mean age of 53.2(±7.2) years, serum irisin levels (log-transformed) were significantly reduced in subjects with MetS and raised FPG than their control groups (p = 0.034 and 0.041, respectively). After adjustment for potential confounders, serum irisin was significantly associated with reduced risks of MetS and raised FPG, with odds ratios (ORs) (95% CI) per standard deviation of log-transformed irisin of 0.796 (0.505–0.959, p = 0.027) and 0.873 (0.764–0.998, p = 0.046), respectively. Associations of irisin with raised BP, raised TG and reduced HDL were not statistically significant ((ORs) (95% CI): 0.733(0.454–1.182, p = 0.202), 0.954(0.838–1.086, p = 0.478) and 1.130(0.980–1.302, p = 0.092), respectively). Stepwise multivariable linear regression analysis showed that fasting insulin, HbA1c and albumin/globulin ratio were negatively associated with serum irisin level with statistical significance (all p-values <0.05) and waist circumference was negatively associated with serum risin with marginally statistical significance (p = 0.055). These results imply that irisin may play an important role in insulin resistance and MetS and should be confirmed in future prospective studies.     

Metabolic Syndrome in South African Patients with Severe Mental Illness: Prevalence and Associated Risk Factors

Background

There is a surge of cardiovascular disease (CVD) in Africa. CVD is the leading cause of mortality among patients with severe mental illness (SMI) in developed countries, with little evidence from the African context.

Objective

To determine the prevalence and risk factors for MetS among South African patients with SMI.

Method

In a cross sectional study, individuals with SMI treated with antipsychotics and a control group without a mental illness, matched for age, gender and ethnicity were evaluated for MetS using the 2009 Joint Interim statement (JIS) criteria.

Results

Of the 276 study group subjects, 65.9% were male, 84.1% black African, 9.1% white, 5.4% of Indian descent and 1.5% coloured (mixed race) with a mean age of 34.7 years (±12.5). Schizophrenia was the most common diagnosis (73.2%) and 40% were taking first generation antipsychotics. The prevalence of MetS was 23.2% (M: 15.4%, F: 38.3%) in the study group and 19.9% (M: 11.9%, F: 36.3%) in the control group (p = 0.4). MetS prevalence was significantly higher in study subjects over 55 years compared to controls (p = 0.03). Increased waist circumference (p< 0.001) and low high density lipoprotein (HDL) cholesterol (p = 0.003) were significantly more prevalent in study subjects compared to controls. In study subjects, risk factors associated with MetS included age (OR: 1.09, 95% CI 1.06–1.12, p < 0.001), female gender (OR: 2.19, 95% CI 1.06–4.55, p = 0.035) and Indian descent (OR: 5.84, 95% CI 1.66–20.52, p = 0.006) but not class of antipsychotic (p = 0.26).

Conclusion

The overall MetS prevalence was not increased in patients with SMI compared to controls; however, the higher prevalence of the individual components (HDL cholesterol and waist circumference) suggests an increased risk for CVD, especially in patients over 55 years.     

Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients

The aim of this study was to investigate whether insulin resistance is independently associated with early manifestations of atherosclerosis. To this end, 176 normotensive offspring of type 2 diabetic patients were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity. Early atherosclerosis was studied by ultrasonography of the common carotid artery. Of the total 176 subjects, 145 were glucose tolerant, 18 had impaired fasting glucose, and 13 had impaired glucose tolerance. Univariate correlations showed that age, body mass index, waist, blood pressure, 2-h postchallenge glucose, fasting insulin, triglycerides, interleukin-6, fibrinogen, and white blood cell count were significantly correlated with carotid intima-media thickness (IMT), whereas HDL cholesterol and glucose disposal showed a negative correlation. A stepwise multivariate regression analysis including sex, age, waist circumference, smoking status, systolic blood pressure, diastolic blood pressure, triglyceride, HDL cholesterol, 2-h postchallenge glucose, plasma IL-6, fibrinogen, white blood cell count, insulin-stimulated glucose disposal, and fasting insulin showed that the four variables that remained significantly associated with carotid IMT were waist circumference, insulin-stimulated glucose disposal, white blood cell count, and diastolic blood pressure, accounting for 33.7% of its variation. These findings support the concept that insulin sensitivity, rather than plasma insulin levels, is associated with early atherosclerosis in nondiabetic normotensive offspring of type 2 diabetic patients.     

Heritability and genetic correlations of metabolic disease-related phenotypes in Mexico: preliminary report from the GEMM Family Study

Cardiovascular disease (CVD) is a major cause of mortality in the Republic of Mexico, and metabolic syndrome, a complex of CVD risk factors, is increasingly prevalent. To date, however, there have been few studies of the genetic epidemiology of metabolic syndrome in Mexico. As a first step in implementing the GEMM Family Study, a large, multicenter collaborative study, we recruited 375 individuals in 21 extended families, without ascertainment on disease, at 9 medical institutions across Mexico. Participants were measured for anthropometric (stature, weight, waist circumference) and hemodynamic (blood pressure, heart rate) phenotypes; glucose, cholesterol, and triglyceride levels were measured in fasting blood. Variance components-based quantitative genetic analyses were performed using SOLAR. All phenotypes except diastolic blood pressure were significantly heritable. Consistent with the definition of metabolic syndrome, many phenotypes exhibited significant environmental correlation, and significant genetic correlations were found between measures of adiposity and fasting glucose and fasting triglyceride levels. These preliminary data represent the first heritability estimates for many of these phenotypes in the Republic of Mexico and indicate that this study design offers excellent power for future gene discovery relative to metabolic disease.     

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors: a meta-analysis

Objectives

To investigate which anthropometric adiposity measure has the strongest association with cardiovascular disease (CVD) risk factors in Caucasian men and women without a history of CVD.

Design

Systematic review and meta-analysis.

Methods

We searched databases for studies reporting correlations between anthropometric adiposity measures and CVD risk factors in Caucasian subjects without a history of CVD. Body mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage were considered the anthropometric adiposity measures. Primary CVD risk factors were: systolic blood pressure, diastolic blood pressure, high density lipoprotein (HDL) cholesterol, triglycerides and fasting glucose. Two independent reviewers performed abstract, full text and data selection.

Results

Twenty articles were included describing 21,618 males and 24,139 females. Waist circumference had the strongest correlation with all CVD risk factors for both men and women, except for HDL and LDL in men. When comparing BMI with waist circumference, the latter showed significantly better correlations to CVD risk factors, except for diastolic blood pressure in women and HDL and total cholesterol in men.

Conclusions

We recommend the use of waist circumference in clinical and research studies above other anthropometric adiposity measures, especially compared with BMI, when evaluating CVD risk factors.     

Associations of iron status with breast cancer risk factors in adult women: Findings from National Health and Nutrition Examination Survey 2017–2018

ObjectiveThis study examined the association between iron status and a set of breast cancer risk factors among U.S. adult women aged 20–80 years.MethodsData from National Health and Nutrition Examination Survey (2017–2018) were used to examine the relation between serum ferritin, serum iron and transferrin saturation with a set of breast cancer risk factors [body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin and HOMA-IR]. The multivariable linear regressions were used controlling for age, race/ethnicity, menopause status, education level, smoking status, alcohol consumption, physical activity, high-sensitivity C-reactive protein (hsCRP) and total energy intake.ResultsHbA1c, BMI and waist circumference data were available for 1902 women with a fasting sample (n = 913) for fasting plasma glucose, insulin and HOMA-IR. Transferrin saturation had significant, inverse associations with BMI, waist circumference and HbA1c. The size of difference observed were that participants in the fourth quartile of transferrin saturation had a 4.50 kg/m² smaller BMI, a 9.36 cm smaller waist circumference and a 0.1 % lower HbA1c level than participants in the first quartile. Similarly, serum iron concentrations were inversely associated with BMI and waist circumference. In addition, serum iron had significant, inverse associations with insulin and HOMA-IR. Sensitivity analyses among men gave similar results. For serum ferritin, there was a trend towards a positive association between waist circumference, HbA1c and fasting plasma glucose with serum ferritin. However, the associations did not reach statistical significance among women.ConclusionsIron status may impact breast cancer risk via effects on adiposity or glucose metabolism. The findings should be confirmed with further prospective data.     

Low Fasting Triglycerides: Hallmark of the Healthy Large Hip?

Body fat distribution modulates risk for type 2 diabetes mellitus. We evaluated potentially involved metabolic risk factors. In a population of 282 male and 157 female healthy subjects (data from the San Antonio and the European Group of Insulin Resistance (EGIR) study cohorts), we evaluated associations between body fat distribution (assessed by waist and hip circumference) and parameters of lipid‐ and glucose metabolism, including clamp measurements of insulin sensitivity. After stratification for BMI, fasting triglycerides were lower in the presence of a large hip, and higher in a large waist. Persons with the largest BMI (3rd tertile) showed a difference in triglyceride levels of 1.5 vs. 2.4 mmol/l in large vs. small hip circumference groups (P < 0.038), and a difference of 1.5 vs. 1.2 mmol/l in large vs. small waist circumference groups (P < 0.025). A similar analysis did not reveal a difference in insulin sensitivity. Linear regression analyses confirmed the findings; they revealed negative associations between triglycerides and hip, and (for women borderline statistically significant) positive associations between triglycerides and waist, after adjustment for BMI, mutual confounding, and age (β ± s.e.; men: ?0.48 ± 0.005, P < 0.001, and 0.21 ± 0.005, P < 0.05; women: ?0.78 ± 0.007, P < 0.001, and 0.24 ± 0.005, P < 0.065), respectively. Linear regression analyses revealed similar opposite associations with high‐density lipoprotein (HDL)‐cholesterol, though not with glucose, insulin, or insulin sensitivity as measured with the clamp method. In our study population of healthy persons, body fat distribution is associated with fasting triglycerides and HDL‐cholesterol, and not with insulin sensitivity. Metabolic risk of unfavorable body fat distribution may be modulated by lower triglyceride storage capacity.     

Combined Effects of Smoking and Alcohol on Metabolic Syndrome: The LifeLines Cohort Study

Introduction

The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its individual components.

Methods

64,046 participants aged 18–80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMI<25, normal weight; BMI 25–30, overweight; BMI≥30 kg/m², obese). MetS was defined according to the revised criteria of the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III). Within each BMI class and smoking subgroup (non-smoker, former smoker, <20 and ≥20 g tobacco/day), the cross-sectional association between alcohol and individual MetS components was tested using regression analysis.

Results

Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7–71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values<0.001). HDL cholesterol levels were lower when they were also a former or current smoker (<20 and ≥20 g tobacco/day). Consumption of ≤1 drink/day indicated a trend towards lower triglyceride levels (non-significant). Concurrent use alcohol (>1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks.

Conclusion

Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS.     

The Terneuzen Birth Cohort: BMI change between 2 and 6 years is most predictive of adult cardiometabolic risk

Background

We recently reported the age interval 2–6y being the earliest and most critical for adult overweight. We now aim to determine which age intervals are predictive of cardiometabolic risk at young adulthood.

Methods and Findings

We analyzed data from 642 18–28 years olds from the Terneuzen Birth Cohort. Individual BMI SDS trajectories were fitted by a piecewise linear model. By multiple regression analyses relationships were assessed between subsequent conditional BMI SDS changes and components of the metabolic syndrome (MetS), skinfold thickness and hsCRP at young adulthood. Results were adjusted for gender and age, and other confounders. Gender was studied as an effect modifier. All BMI SDS changes throughout childhood were related to waist circumference and skinfold thickness. No other significant relationship was found before the age of 2 years, except between the BMI SDS change 0–1y and hsCRP. Fasting blood glucose was not predicted by any BMI SDS change. BMI SDS change 2–6y was strongly related to most outcome variables, especially to waist circumference (ß 0.47, SE 0.02), systolic and diastolic blood pressure (ß 0.20 SE 0.04 and ß 0.19 SE 0.03), and hsCRP (ß 0.16 SE 0.04). The BMI SDS change 10–18y was most strongly related to HDL cholesterol (ß -0.10, SE 0.03), and triglycerides (ß 0.21, SE 0.03). To a lesser degree, the BMI SDS change 6–10y was related to most outcome variables. BMI SDS changes 2–6y and 10–18y were significantly related to MetS: the OR was respectively 3.39 (95%CI 2.33–4.94) and 2.84 (95%CI 1.94–4.15).

Conclusion

BMI SDS changes from 2y onwards were related to cardiometabolic risk at young adulthood, the age interval 2–6y being the most predictive. Monitoring and stabilizing the BMI SDS of children as young as 2–6y may not only reverse the progression towards adult overweight, but it may also safeguard cardiometabolic status.     

Television viewing and incident cardiovascular disease: prospective associations and mediation analysis in the EPIC Norfolk Study

Background

Although television viewing time is detrimentally associated with intermediate cardiovascular risk factors, the relationship with incident total (i.e. combined fatal and non-fatal) cardiovascular disease (CVD), non-fatal CVD and coronary heart disease is largely unknown. This study examined whether television viewing time is associated with these three outcomes, independently of physical activity energy expenditure and other confounding variables.

Methodology/Principal Findings

A population-based cohort of 12,608 men and women (aged 61.4±9.0), free from stroke, myocardial infarction and cancer at baseline in 1998–2000 were followed up until 2007 (6.9±1.9 years). Participants self-reported education, smoking, alcohol use, antihypertensive, lipid lowering and antidepressant medication, disease history, total energy intake, sleep duration, physical activity and television viewing. BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol and glycated haemoglobin (HbA_1c) were measured by standardized procedures; a clustered metabolic risk score was constructed. Every one hour/day increase in television viewing was associated with an increased hazard for total (HR = 1.06, 95%CI = 1.03–1.08; 2,620 cases), non-fatal CVD (HR = 1.06, 95%CI = 1.03–1.09; 2,134 cases), and coronary heart disease (HR = 1.08, 95%CI = 1.03–1.13; 940 cases), independent of gender, age, education, smoking, alcohol, medication, diabetes status, CVD family history, sleep duration and physical activity energy expenditure. Energy intake, BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol, HbA_1c and the clustered metabolic risk score only partially mediated these associations.

Conclusions

These results indicate that the most prevalent leisure time (sedentary) behaviour, television viewing, independently contributes to increased CVD risk. Recommendations on reducing television viewing time should be considered.     

Dyslipidemia in PCOS

Life-long apolipoprotein lipid metabolic dysfunction in women with PCOS exaggerates the risk for cardiovascular disease (CVD) with aging. The dysfunction has involved insulin resistance (IR), which occurs in most women with PCOS. Women with PCOS have androgen excess, IR, variable amounts of estrogen exposure, and many environmental factors, all of which can influence lipid metabolism. On average, women with PCOS were higher triglyceride [26.39 95% CI (17.24, 35.54)], lower HDL-cholesterol [6.41 95% CI (3.69, 9.14)], and higher non HDL cholesterol levels [18.82 95% CI (15.53, 22.11)] than their non-PCOS counterparts. They have higher ApoCIII/ApoCII ratios and higher ApoCI even if they are not obese. ApoC1 elevation in women with PCOS needs to be further evaluated as a marker of dysfunction and potential CVD risk. ApoB measurements track with non-HDL cholesterol as a surrogate for increased atherogenic circulating small LDL particles. Elevated triglycerides and waist circumference predict CVD risk and women with PCOS often have these phenotypes. Diet and exercise interventions followed by selective lipid lowering medications are encouraged to normalize the dyslipidemia.