High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development

Background

Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years.

Methods

From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids.

Results

The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P<0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18∶1n-9 as well as total MUFA (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (P_trend<0.001), n-6 LCPUFA (P_trend = 0.001), and total LCPUFA (P_trend<0.001) and decreased linearly with the proportions of total MUFA (P_trend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy.

Conclusion

A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant''s immune system.     

Higher Gravidity and Parity Are Associated with Increased Prevalence of Metabolic Syndrome among Rural Bangladeshi Women

Background

Parity increases the risk for coronary heart disease; however, its association with metabolic syndrome among women in low-income countries is still unknown.

Objective

This study investigates the association between parity or gravidity and metabolic syndrome in rural Bangladeshi women.

Methods

A cross-sectional study was conducted in 1,219 women aged 15–75 years from rural Bangladesh. Metabolic syndrome was defined according to the standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between parity and gravidity and metabolic syndrome, with adjustment of potential confounding variables.

Results

Subjects with the highest gravidity (> = 4) had 1.66 times higher odds of having metabolic syndrome compared to those in the lowest gravidity (0-1) (P _trend = 0.02). A similar association was found between parity and metabolic syndrome (P _trend = 0.04), i.e., subjects in the highest parity (> = 4) had 1.65 times higher odds of having metabolic syndrome compared to those in the lowest parity (0-1). This positive association of parity and gravidity with metabolic syndrome was confined to pre-menopausal women (P _trend <0.01). Among the components of metabolic syndrome only high blood pressure showed positive association with parity and gravidity (P _trend = 0.01 and <0.001). Neither Parity nor gravidity was appreciably associated with other components of metabolic syndrome.

Conclusions

Multi parity or gravidity may be a risk factor for metabolic syndrome.     

Age at Menarche and Natural Menopause and Number of Reproductive Years in Association with Mortality: Results from a Median Follow-Up of 11.2 Years among 31,955 Naturally Menopausal Chinese Women

Background

Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.

Methods

We evaluated the effects of age at menarche, age at natural menopause, and number of reproductive years on total and cause-specific mortality among 31,955 naturally menopausal Chinese women who participated in the Shanghai Women''s Health Study, a population-based, prospective cohort study.

Results

A total of 3,158 deaths occurred during a median follow-up of 11.2 years. Results from Cox proportional hazards models showed that younger age at menopause (<46.64 years) was associated with higher risk of total mortality (P_trend  = 0.02). Younger age at menarche (<14 years) was associated with higher risk of mortality from stroke (P_trend  = 0.03) and diabetes (P_trend = 0.02) but lower risk of mortality from respiratory system cancer (P_trend  = 0.01). Women with a shorter reproductive span had lower risk of mortality from gynecological cancers (P_trend = 0.03).

Conclusions

Our study found that menstrual characteristics are important predictors of mortality, suggesting an important role of sex hormones in biological aging.     

Association of Plasma IL-6 and Hsp70 with HRV at Different Levels of PAHs Metabolites

Background

Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with reduced heart rate variability (HRV), a strong predictor of cardiovascular diseases, but the mechanism is not well understood.

Objectives

We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.

Methods

HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas chromatography-mass spectrometry.

Results

We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all P _trend<0.05); and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP) and low frequency (LF) (P _trend = 0.014 and 0.006, respectively). In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all P _trend<0.05), but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN), TP and LF in the low-PAHs metabolites groups (all P _trend<0.05). We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.

Conclusions

In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.     

Seroprevalence of Merkel Cell Polyomavirus in the General Rural Population of Anyang,China

Background

Despite the probably causal link between Merkel cell polyomavirus (MCPyV) infection and Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy, little is known about the seroepidemiology of MCPyV among healthy adults in China.

Methods

Serum antibodies against MCPyV were evaluated by multiplex serology in a population-based study of 5548 adults (including 1587 heterosexual couples) aged 25–65 years who were enrolled from rural Anyang, China in 2007–2009. Univariate and multivariate logistic regression analyses were performed to assess the risk factors for the seropositivity of MCPyV.

Results

The seroprevalence for MCPyV was 61.0%. MCPyV seropositivity was significantly higher in males than in females (64.5% vs. 57.7%, P<0.001), and for both genders, showed a trend of increase with age (Male: P _trend<0.001; Female: P _trend<0.001). Furthermore, among antibody positives, antibody levels of MCPyV increased with advancing age (P _trend = 0.017). MCPyV seropositivity of one spouse was significantly associated with that of the other partner (Adjusted OR = 1.32, 95% CI: 1.07–1.62). However, there was no association between sexual behaviors and the seropositivity of MCPyV.

Conclusions

High seroprevalence of MCPyV was observed in healthy Chinese individuals. Serological evidence suggests that nonsexual horizontal spread of MCPyV can occur among family members, and further research in this regard is needed.     

A Prospective Cohort Study Examining the Associations of Dietary Calcium Intake with All-Cause and Cardiovascular Mortality in Older Chinese Community-Dwelling People

Background

Most epidemiological studies of calcium intake and mortality risk have been conducted in populations with moderate to high calcium intake, and limited studies have focused on populations with low habitual calcium intake (i.e., mean dietary calcium intake <700 mg/d).

Objective

This study investigated the association between dietary calcium intake and death from all causes and cardiovascular disease in Chinese population with low habitual calcium intake.

Design

Data from 3,139 Chinese men and women in a population-based prospective cohort study, aged >=65 years and free of heart diseases or stroke at baseline, were analyzed. Primary outcome measures, identified from the death registry, were death from all causes and cardiovascular disease. Dietary calcium intake assessed using a validated food frequency questionnaire was categorized into sex-specific quartiles. Data on use of supplemental calcium (yes or no) including individual calcium supplements and other calcium containing supplement were collected. Cox regression models adjusted for demographic and lifestyle variables were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI).

Results

During a median of 9.1 years of follow-up, 529 all-cause deaths (344 men, 185 women) and 114 (74 men, 40 women) deaths from cardiovascular disease were identified. An inverse trend between dietary calcium intake and mortality was observed. Compared with the lowest quartile (<458 mg/d for men, <417 mg/d for women), the highest quartile of dietary calcium intake (>762 mg/d for men, >688 mg/d for women) had a significantly reduced risk of all-cause mortality (multivariate HR=0.63, 95% CI=0.49-0.81, P _trend<0.001) but an insignificant decreased risk of cardiovascular mortality (multivariate HR=0.70, 95% CI=0.41-1.21, P _trend=0.228). Similar inverse association was observed when the analyses were stratified on calcium supplemental use.

Conclusions

Higher intake of dietary calcium was associated with reduced risk of all-cause mortality and possibly cardiovascular mortality in Chinese older people with low habitual calcium intake.     

Effect of a High Intake of Conjugated Linoleic Acid on Lipoprotein Levels in Healthy Human Subjects

Background

Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower high-density lipoprotein (HDL) cholesterol, raise low-density lipoprotein (LDL) cholesterol, and increase the risk of coronary heart disease. The effects of trans fatty acids from ruminants are less clear. We investigated the effect on blood lipids of cis-9, trans-11 conjugated linoleic acid (CLA), a trans fatty acid largely restricted to ruminant fats.

Methodology/Principal Findings

Sixty-one healthy women and men were sequentially fed each of three diets for three weeks, in random order, for a total of nine weeks. Diets were identical except for 7% of energy (approximately 20 g/day), which was provided either by oleic acid, by industrial trans fatty acids, or by a mixture of 80% cis-9, trans-11 and 20% trans-10, cis-12 CLA. After the oleic acid diet, mean (± SD) serum LDL cholesterol was 2.68±0.62 mmol/L compared to 3.00±0.66 mmol/L after industrial trans fatty acids (p<0.001), and 2.92±0.70 mmol/L after CLA (p<0.001). Compared to oleic acid, HDL-cholesterol was 0.05±0.12 mmol/L lower after industrial trans fatty acids (p = 0.001) and 0.06±0.10 mmol/L lower after CLA (p<0.001). The total-to–HDL cholesterol ratio was 11.6% higher after industrial trans fatty acids (p<0.001) and 10.0% higher after CLA (p<0.001) relative to the oleic acid diet.

Conclusions/Significance

High intakes of an 80∶20 mixture of cis-9, trans-11 and trans-10, cis-12 CLA raise the total to HDL cholesterol ratio in healthy volunteers. The effect of CLA may be somewhat less than that of industrial trans fatty acids.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00529828","term_id":"NCT00529828"}}NCT00529828     

The Association between Selenium and Other Micronutrients and Thyroid Cancer Incidence in the NIH-AARP Diet and Health Study

Background

Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear.

Methods

We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health – American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50–71 years in 1995–1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index.

Results

With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HR_{Q5 vs Q1}, 1.34; 95% CI, 1.02–1.76; P_trend, <0.01), we observed no evidence of an association between quintile of selenium (HR_{Q5 vs Q1}, 1.23; 95% CI, 0.92–1.65; P_trend, 0.26) or other micronutrient intake and thyroid cancer.

Conclusion

Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis.     

Low Blood Long Chain Omega-3 Fatty Acids in UK Children Are Associated with Poor Cognitive Performance and Behavior: A Cross-Sectional Analysis from the DOLAB Study

Background

Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA), especially DHA (docosahexaenonic acid) are essential for brain development and physical health. Low blood Omega-3 LC-PUFA have been reported in children with ADHD and related behavior/learning difficulties, as have benefits from dietary supplementation. Little is known, however, about blood fatty acid status in the general child population. We therefore investigated this in relation to age-standardized measures of behavior and cognition in a representative sample of children from mainstream schools.

Participants

493 schoolchildren aged 7–9 years from mainstream Oxfordshire schools, selected for below average reading performance in national assessments at age seven.

Method

Whole blood fatty acids were obtained via fingerstick samples. Reading and working memory were assessed using the British Ability Scales (II). Behaviour (ADHD-type symptoms) was rated using the revised Conners’ rating scales (long parent and teacher versions). Associations were examined and adjusted for relevant demographic variables.

Results

DHA and eicosapentaenoic acid (EPA), accounted for only 1.9% and 0.55% respectively of total blood fatty acids, with DHA showing more individual variation. Controlling for sex and socio-economic status, lower DHA concentrations were associated with poorer reading ability (std. OLS coeff. = 0.09, p = <.042) and working memory performance (0.14, p = <.001). Lower DHA was also associated with higher levels of parent rated oppositional behavior and emotional lability (−0.175, p = <.0001 and −0.178, p = <.0001).

Conclusions

In these healthy UK children with below average reading ability, concentrations of DHA and other Omega-3 LC-PUFA were low relative to adult cardiovascular health recommendations, and directly related to measures of cognition and behavior. These findings require confirmation, but suggest that the benefits from dietary supplementation with Omega-3 LC-PUFA found for ADHD, Dyspraxia, Dyslexia, and related conditions might extend to the general school population.     

Correlates of 25-Hydroxyvitamin D among Chinese Breast Cancer Patients

Background

Few studies have investigated vitamin D status in association with modifiable lifestyle factors and clinical characteristics among breast cancer patients, with no studies among Chinese women, who may be at higher risk of vitamin D deficiency. We aimed to evaluate circulating 25-hydroxyvitamin D (25(OH)D) levels in association with clinical and lifestyle factors among 1,940 Chinese breast cancer patients.

Methods

Participants included breast cancer cases aged 22–77 from a population-based case-control study conducted in Shanghai, China during 1996–1998 (n = 1,044) and 2002–2005 (n = 896). Circulating 25(OH)D levels were measured in plasma samples (95% collected ≤6 months post-diagnosis). Prevalence ORs and 95% CIs were derived from multinomial logistic regression models, adjusting for age, season, and other factors.

Results

About 23% and 48% of women were vitamin D deficient (<30 nmol/L) or insufficient (30–50 nmol/L), respectively. Tumor characteristics were not associated with vitamin D status. Higher BMI was associated with increased odds of vitamin D deficiency (ORs (95% CIs): 1 (reference), 1.12 (0.85,1.47), and 1.57 (1.02,2.42), for <23, 23–<27.5, and ≥27.5 kg/m², respectively, P_trend <0.06). Total physical activity was associated with reduced odds of vitamin D deficiency (ORs (95% CIs):1 (reference), 0.84 (0.59,1.20), 0.65 (0.45,0.93), and 0.69 (0.48,1.00), for <7.65, 7.65–<10.6, 10.6–<13.5, ≥13.5 MET-hours/day, respectively, P_trend <0.02). Smoking was associated with vitamin D insufficiency and deficiency (ORs (95% CIs): 2.50 (1.07,5.84) and 2.78 (1.11,6.95), respectively).

Conclusions

In the largest study to date, the prevalence of low vitamin D status was high among Chinese breast cancer patients and associated with higher BMI, smoking, and lower physical activity. Our findings support careful monitoring of vitamin D status and recommendations for supplementation and other lifestyle modifications that may improve vitamin D status in breast cancer patients.     

Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective

To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC).

Methods

The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate.

Results

Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, P_cor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, P_cor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, P_cor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, P_cor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, P_cor<0.05) were the cutoff values for screening ≥50% carotid stenosis.

Conclusions

Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.     

The Association between Subclinical Atherosclerosis and Uterine Fibroids

Objective(s)

To explore the atherogenic hypothesis of uterine fibroids among Chinese women.

Methods

In a case-control study, 335 patients confirmed by ultrasound or hysterectomy surgery and 539 controls were enrolled between October 1, 2009 and April 1, 2012. Unconditional logistic regressions were used to calculate the odds ratios (ORs) for the associations of subclinical atherogenic and cardiovascular risk parameters with uterine fibroids in the overall case group and hysterectomy-confirmed case group, respectively.

Results

Higher level of ankle-brachial index (ABI) was independently associated with increased odds of uterine fibroids. The odds of UF among women in the highest tertile of ABI were 1.88 times higher (95%CI: 1.17, 3.02, P_trend = 0.008) compared to those in the lowest tertile. The serum concentration of homocysteine was inversely related to fibroids (middle vs. low: OR 0.56, 95%CI: 0.36, 0.85; high vs. low: OR 0.50, 95% CI: 0.32, 0.79; P_trend = 0.002). In the hysterectomy-confirmed group, an inverse association was suggested between high-density lipoprotein cholesterol (HDL-C) and fibroids (OR 0.46, 95% CI: 0.25, 0.84, P_trend = 0.014). Moreover, the effect of homocysteine concentration was not observed in this group.

Conclusion(s)

These findings suggest that women with uterine fibroids might have an increased risk of subclinical atherosclerosis.     

Global Metabolomic Profiling Reveals an Association of Metal Fume Exposure and Plasma Unsaturated Fatty Acids

Background

Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans.

Objectives

To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure.

Methods

The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry.

Results

Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM_2.5) exposure (p<0.05). The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [(95% CI) = −0.013(−0.022∼−0.004); p = 0.005], docosapentaenoic acid n₃ [(95% CI) = −0.010(−0.018∼−0.002); p = 0.017], and docosapentaenoic acid n₆ [(95% CI) = −0.007(−0.013∼−0.001); p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p _Study−₂₀₁₁ = 0.025; p _Study−₂₀₁₂ = 0.021; p _Combined = 0.009). The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders.

Conclusions

High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.     

Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative

Introduction

Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD.

Methods

Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUV_max), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with β-coefficients (β) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors.

Results

Vascular inflammation (measured as SUV_max) was greater (P < 0.001) in patients with sacroiliitis (mean ± SD = 7.33 ± 2.09) defined by CT compared to those without sacroiliitis (6.39 ± 1.49, P = 0.038). There were associations between PsA and aortic inflammation (β = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (β = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (χ² = 124.6, P < 0.001).

Conclusions

Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings.

Electronic supplementary material

The online version of this article (doi:10.1186/ar4676) contains supplementary material, which is available to authorized users.     

Influence of the ABCG2 gout risk 141?K allele on urate metabolism during a fructose challenge

Introduction

Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.

Methods

Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution. Data were analyzed based on the presence or absence of the ABCG2 141 K gout risk allele.

Results

The 141 K risk allele was present in 23 participants (31%). Overall, serum urate (SU) concentrations during the fructose load were similar in those with and without the 141 K allele (P_SNP = 0.15). However, the 141 K allele was associated with a smaller increase in SU following fructose intake (P_SNP <0.0001). Those with the 141 K allele also had a smaller increase in serum glucose following the fructose load (P_SNP = 0.002). Higher fractional excretion of uric acid (FEUA) at baseline and throughout the fructose load was observed in those with the 141 K risk allele (P_SNP <0.0001). However, the change in FEUA in response to fructose was not different in those with and without the 141 K risk allele (P_SNP = 0.39). The 141 K allele effects on serum urate and glucose were more pronounced in Polynesian participants and in those with a body mass index ≥25 kg/m².

Conclusions

In contrast to the predicted responses for a hyperuricemia/gout risk allele, the 141 K allele is associated with smaller increases in SU and higher FEUA following a fructose load. The results suggest that ABCG2 interacts with extra-renal metabolic pathways in a complex manner to regulate SU and gout risk.

Clinical Trials Registration

The study was registered by the Australian Clinical Trials Registry (ACTRN12610001036000).     

Effect of High- versus Low-Intensity Supervised Aerobic and Resistance Training on Modifiable Cardiovascular Risk Factors in Type 2 Diabetes; The Italian Diabetes and Exercise Study (IDES)

Background

While current recommendations on exercise type and volume have strong experimental bases, there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes.

Objective

To compare the effects of moderate-to-high intensity (HI) versus low-to-moderate intensity (LI) training of equal energy cost, i.e. exercise volume, on modifiable cardiovascular risk factors.

Design

Pre-specified sub-analysis of the Italian Diabetes and Exercise Study (IDES), a randomized multicenter prospective trial comparing a supervised exercise intervention with standard care for 12 months (2005–2006).

Setting

Twenty-two outpatient diabetes clinics across Italy.

Patients

Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling (n = 303).

Interventions

Subjects were randomized by center to LI (n = 142, 136 completed) or HI (n = 161, 152 completed) progressive aerobic and resistance training, i.e. at 55% or 70% of predicted maximal oxygen consumption and at 60% or 80% of predicted 1-Repetition Maximum, respectively, of equal volume.

Main Outcome Measure(s)

Hemoglobin (Hb) A_1c and other cardiovascular risk factors; 10-year coronary heart disease (CHD) risk scores.

Results

Volume of physical activity, both supervised and non-supervised, was similar in LI and HI participants. Compared with LI training, HI training produced only clinically marginal, though statistically significant, improvements in HbA_1c (mean difference −0.17% [95% confidence interval −0.44,0.10], P = 0.03), triglycerides (−0.12 mmol/l [−0.34,0.10], P = 0.02) and total cholesterol (−0.24 mmol/l [−0.46, −0.01], P = 0.04), but not in other risk factors and CHD risk scores. However, intensity was not an independent predictor of reduction of any of these parameters. Adverse event rate was similar in HI and LI subjects.

Conclusions

Data from the large IDES cohort indicate that, in low-fitness individuals such as sedentary subjects with type 2 diabetes, increasing exercise intensity is not harmful, but does not provide additional benefits on cardiovascular risk factors.

Trial Registration

www.ISRCTN.org ISRCTN-04252749.     

Effects of a Brown Beans Evening Meal on Metabolic Risk Markers and Appetite Regulating Hormones at a Subsequent Standardized Breakfast: A Randomized Cross-Over Study

Background

Dietary prevention strategies are increasingly recognized as essential to combat the current epidemic of obesity and related metabolic disorders. The purpose of the present study was to evaluate the potential prebiotic effects of indigestible carbohydrates in Swedish brown beans (Phaseolus vulgaris var. nanus) in relation to cardiometabolic risk markers and appetite regulating hormones.

Methods

Brown beans, or white wheat bread (WWB, reference product) were provided as evening meals to 16 healthy young adults in a randomised crossover design. Glucose, insulin, appetite regulatory hormones, GLP-1, GLP-2, appetite sensations, and markers of inflammation were measured at a following standardised breakfast, that is at 11 to 14 h post the evening meals. Additionally, colonic fermentation activity was estimated from measurement of plasma short chain fatty acids (SCFA, including also branched chain fatty acids) and breath hydrogen (H₂) excretion.

Results

An evening meal of brown beans, in comparison with WWB, lowered blood glucose (−15%, p<0.01)- and insulin (−16%, p<0.05) responses, increased satiety hormones (PYY 51%, p<0.001), suppressed hunger hormones (ghrelin −14%, p<0.05), and hunger sensations (−15%, p = 0.05), increased GLP-2 concentrations (8.4%, p<0.05) and suppressed inflammatory markers (IL-6 −35%, and IL-18 −8.3%, p<0.05) at a subsequent standardised breakfast. Breath H₂ (141%, p<0.01), propionate (16%, p<0.05), and isobutyrate (18%, P<0.001) were significantly increased after brown beans compared to after WWB, indicating a higher colonic fermentative activity after brown beans.

Conclusions

An evening meal with brown beans beneficially affected important measures of cardiometabolic risk and appetite regulatory hormones, within a time frame of 11–14 h, in comparison to a WWB evening meal. Concentrations of plasma SCFA and H₂ were increased, indicating involvement of colonic fermentation. Indigestible colonic substrates from brown beans may provide a preventive tool in relation to obesity and the metabolic syndrome.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01706042","term_id":"NCT01706042"}}NCT01706042     

Randomised Double-Blind Comparison of Placebo and Active Drugs for Effects on Risks Associated with Blood Pressure Variability in the Systolic Hypertension in Europe Trial

Background

In the Systolic Hypertension in Europe trial ({"type":"clinical-trial","attrs":{"text":"NCT02088450","term_id":"NCT02088450"}}NCT02088450), we investigated whether systolic blood pressure variability determines prognosis over and beyond level.

Methods

Using a computerised random function and a double-blind design, we randomly allocated 4695 patients (≥60 years) with isolated systolic hypertension (160–219/<95 mm Hg) to active treatment or matching placebo. Active treatment consisted of nitrendipine (10–40 mg/day) with possible addition of enalapril (5–20 mg/day) and/or hydrochlorothiazide (12.5–25.0 mg/day). We assessed whether on-treatment systolic blood pressure level (SBP), visit-to-visit variability independent of the mean (VIM) or within-visit variability (WVV) predicted total (n = 286) or cardiovascular (n = 150) mortality or cardiovascular (n = 347), cerebrovascular (n = 133) or cardiac (n = 217) endpoints.

Findings

At 2 years, mean between-group differences were 10.5 mm Hg (p<0.0001) for SBP, 0.29 units (p = 0.20) for VIM, and 0.07 mm Hg (p = 0.47) for WVV. Active treatment reduced (p≤0.048) cardiovascular (−28%), cerebrovascular (−40%) and cardiac (−24%) endpoints. In analyses dichotomised by the median, patients with low vs. high VIM had similar event rates (p≥0.14). Low vs. high WVV was not associated with event rates (p≥0.095), except for total and cardiovascular mortality on active treatment, which were higher with low WVV (p≤0.0003). In multivariable-adjusted Cox models, SBP predicted all endpoints (p≤0.0043), whereas VIM did not predict any (p≥0.058). Except for an inverse association with total mortality (p = 0.042), WVV was not predictive (p≥0.15). Sensitivity analyses, from which we excluded blood pressure readings within 6 months after randomisation, 6 months prior to an event or both were confirmatory.

Conclusions

The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP. Higher blood pressure level, but not higher variability, predicted risk.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02088450","term_id":"NCT02088450"}}NCT02088450     

Fasting Whole Blood Fatty Acid Profile and Risk of Type 2 Diabetes in Adults: A Nested Case Control Study

Objective

to determine the association of fasting whole blood fatty acid concentrations with incidence of type 2 diabetes in adults.

Methods

A nested case-control study of 187 subjects from a cohort of men and women aged 55–85 years from the Hunter Region, New South Wales, Australia. Fasting whole blood fatty acids were measured using gas chromatography and incidence of type 2 diabetes was ascertained by self-reported questionnaire at the study follow-up.

Results

After adjustment for potential confounding variables, positive associations with type 2 diabetes were seen for dihomo-gamma-linolenic acid (DGLA) (OR = 1.04, 95% CI:1.01–1.07, P = 0.01); arachidonic acid (ARA) (OR = 1.01, 95% CI:1.00–1.01, P = 0.002); alpha-linolenic acid (ALA) (OR = 1.10, 95% CI: 1.03–1.18, P = 0.01); eicosapentaenoic acid (EPA) (OR = 1.05, 95% CI:1.02–1.08, P = 0.001); and docosahexaenoic acid (DHA) (OR = 1.03, 95% CI:1.02–1.05, P<0.0001). Lignoceric acid is significantly associated with lower type 2 diabetes risk (OR = 0.95, 95% CI: 0.92–0.99, P = 0.01).

Conclusion

These data suggest that higher fasting whole blood concentrations of omega-6 polyunsaturated fatty acids (n-6PUFA) (ARA and DGLA) as well as omega-3 polyunsaturated fatty acid (n-3PUFA) (ALA, EPA, and DHA) are associated with an increased risk of diabetes, whereas increased fasting whole blood concentrations of lignoceric acid is inversely associated with diabetes risk.     

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic,Statin-Treated Subjects

Background

Oxylipins mediate inflammation, vascular tension, and more. Their presence in lipoproteins could explain why lipoproteins mediate nearly identical activities.

Methods

To determine how oxylipins are distributed in the lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids alter them in a manner consistent with improved cardiovascular health, we recruited 15 dyslipidemic subjects whose levels of low density lipoprotein cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200–499 mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and EpDPEs).

Results

At baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs) were most abundant in plasma with the greatest fraction of total abundance (mean |95% CI|) being carried in high density lipoproteins (HDL); 42% |31, 57| followed by very low density lipoproteins (VLDL); 27% |20, 36|; and LDL 21% |16, 28|. EPA- and DHA-derived oxylipins constituted less than 11% of total. HDL carried alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA-derived oxylipins across lipoprotein classes (−23% |−33, −12|, p = 0.0003), and expanded EPA−(322% |241, 422|, p<0.0001) and DHA-derived oxylipins (123% |80, 176|, p<0.0001).

Conclusions

Each lipoprotein class carries a unique oxylipin complement. P-OM3 treatment alters the oxylipin content of all classes, reducing pro-inflammatory and increasing anti-inflammatory species, consistent with the improved inflammatory and vascular status associated with the treatment.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00959842","term_id":"NCT00959842"}}NCT00959842