Several animal and human studies have shown that zinc is associated with cellular damage and cardiac dysfunction. This study aims to investigate dietary zinc and the zinc-iron ratio, as predictors of ...incident cardiovascular disease (CVD) in a large longitudinal study of mid-age Australian women (aged 50-61 years). Data was self-reported and validated food frequency questionnaires were used to assess dietary intake. Energy-adjusted zinc was ranked using quintiles and predictors of incident CVD were examined using stepwise logistic regression. After six years of follow-up, 320 incident CVD cases were established. A positive association between dietary zinc intake, zinc-iron ratio and risk of CVD was observed even after adjusting for potential dietary and non-dietary confounders. Compared to those with the lowest quintile of zinc, those in the highest quintile (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI) = 1.08-2.62) and zinc-iron ratio (OR = 1.72, 95% CI = 1.05-2.81) had almost twice the odds of developing CVD (
trend = 0.007). This study shows that high dietary zinc intake and zinc-iron ratio is associated with a greater incidence of CVD in women. Further studies are required detailing the source of zinc and iron in diet and their precise roles when compared to other essential nutrients.
Nitric oxide (NO) facilitates anti-atherosclerotic effects. Vegetables are a major source of dietary nitrate. Experimental data indicates that dietary nitrate can significantly reduce major risk ...factors for atherosclerosis and subsequent cardiovascular disease (CVD), as nitrate can be metabolized to produce NO via the nitrate-nitrite-NO pathway. The purpose of this study was to prospectively investigate the association between habitual dietary nitrate intakes and the incidence of self-reported CVD-related complications within a representative sample of middle-aged Australian women (1946⁻1951 cohort of the Australian Longitudinal Study on Women's Health). Women free from disease at baseline who had completed the food frequency questionnaire data were included. Generalized estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) across quartiles for nitrate intakes. Of the 5324 women included for analysis, there were 1951 new cases of CVD-related complications over 15-years of follow-up. Women reporting higher total dietary nitrate intakes (Q4 > 78.2 mg/day) and vegetable nitrate intakes (Q4 > 64.4 mg/day) were 25% and 27% reduced risk of developing CVD-related complications respectively, compared with women reporting low total (Q1 < 45.5 mg/day) and vegetable nitrate intakes (Q1 < 34.8 mg/day). Our findings were consistent with other observational data indicating that dietary nitrate may explain some of the cardiovascular benefits of vegetable consumption.
A number of studies have investigated two common polymorphisms in the β2-adrenoceptor gene, Arg/Gly16 and Gln/Glu27, in relation to asthma susceptibility. The authors performed a meta-analysis of ...each polymorphism, as well as haplotype analysis, for adult and pediatric populations separately, using published data, supplemented by additional data requested from the original authors. Individual analysis detected no effect of Arg/Gly16 in adults but did suggest a recessive protective effect of Gly16 for children, with an odds ratio of 0.71 (95% confidence interval (CI): 0.53, 0.96) compared with the other genotypes. Results for Gln/Glu27 in adults seem to indicate that heterozygotes are at decreased risk of asthma than either homozygote (odds ratio = 0.73, 95% CI: 0.62, 0.87), although the studies are heterogeneous; in children, the Glu/Glu genotype has a decreased risk of asthma (odds ratio = 0.60, 95% CI: 0.35, 0.99) compared with the other genotypes. Despite the proximity of these two polymorphic sites, the linkage disequilibrium coefficient of 0.41 was not high (p < 0.001). Haplotype analysis suggests that there may be an interaction between the two sites, with a lower risk of asthma associated with the Glu27 allele (compared with Gln27), and that this risk is modified by the allele at position 16.
The present study aimed to determine the ability of two diet quality scores to predict the incidence of type 2 diabetes in women. The study population comprised a nationally representative sample of ...8370 Australian middle-aged (45-50 years) women participating in the ALSWH (Australian Longitudinal Study on Women's Health), who were free of diabetes and completed FFQ at baseline. The associations between the Australian Recommended Food Score (ARFS) and Dietary Guideline Index (DGI) with type 2 diabetes risk were assessed using multiple logistic regression models, adjusting for sociodemographic characteristics, lifestyle factors and energy intake. During 6 years of follow-up, 311 incident cases of type 2 diabetes were reported. The DGI score was inversely associated with type 2 diabetes risk (OR comparing the highest with the lowest quintile of DGI was 0·51; 95% CI 0·35, 0·76; P for trend = 0·01). There was no statistically significant association between the ARFS and type 2 diabetes risk (OR comparing the highest with the lowest quintile of ARFS was 0·99; 95% CI 0·68, 1·43; P for trend = 0·42). The results of the present prospective study indicate that the DGI score, which assesses compliance with established dietary guidelines, is predictive of type 2 diabetes risk in Australian women. The risk of type 2 diabetes among women in the highest quintile of DGI was approximately 50% lower than that in women in the lowest quintile. The ARFS was not significantly predictive of type 2 diabetes.
Among plasma metabolites linked with a health-conscious food pattern (HCFP) identified in the Malmö Diet and Cancer epidemiological study, circulating ergothioneine (ERT) concentrations exhibited the ...strongest independent association with reduced risk of cardiometabolic disease and all-cause mortality and were also related to alcohol consumption. Thus, we first assessed whether alcohol intake and ERT were similarly associated in participants of the Hunter Community Study (HCS) that did not follow an HCFP-based diet. Then, we sought to identify the presence of associations with some biomarkers associated with cardiovascular disease. In a multivariable adjusted, robust regression analysis, compared to non-drinkers, safe drinkers had, on average, a serum ERT concentration 0.112 (95% CI: 0.0–0.225; P = 0.051) units higher and moderate-hazardous drinkers had a serum ERT concentration 0.240 (95% CI: 0.093–0.387; P = 0.001) units higher. Moreover, stepwise multiple linear regression shows that age (P = 0.025), and asymmetric dimethyl-l-arginine (ADMA) (P = 0.001) were independently associated with serum ERT concentrations, independently of age, sex, education, household income, marital status, and health status of participants, or possible alcohol-induced organ damage. The relationship between ERT and ADMA offers a potential explanation for the interplay between ERT, and decreased risk of cardiometabolic disease and all-cause mortality. Also, it provides new mechanistic insights into the association between alcohol consumption and cardiovascular diseases, possibly mediated by ADMA metabolic pathways.
•Serum ergothioneine concentrations significantly increased with increased alcohol intake.•Compared to safe and non-drinkers, moderate to hazardous drinkers showed the highest serum ergothioneine concentration.•Serum ergothioneine was significantly and inversely associated with asymmetric dimethyl-l-arginine.
STUDY QUESTION
Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk?
SUMMARY ANSWER
We found evidence for strong association between ...IL1A SNPs and endometriosis risk.
WHAT IS KNOWN ALREADY
Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis.
STUDY DESIGN, SIZE, DURATION
We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014.
PARTICIPANTS/MATERIALS, SETTING, METHODS
By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed.
MAIN RESULTS AND THE ROLE OF CHANCE
All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with endometriosis at a nominal P < 0.05 in our independent Japanese sample. Fixed-effect meta-analysis of the eight SNPs for moderate-to-severe endometriosis produced a genome-wide significant association for rs6542095 (odds ratio = 1.21; 95% confidence interval = 1.13–1.29; P = 3.43 × 10−8).
LIMITATIONS, REASONS FOR CAUTION
The meta-analysis for moderate-to-severe endometriosis included results of moderate-to-severe endometriosis cases from our European data sets and all endometriosis cases from the Japanese data sets, as disease stage information was not available for endometriosis cases in the Japanese data sets.
WIDER IMPLICATIONS OF THE FINDINGS
SNP rs6542095 is located ∼2.3 kb downstream of the IL1A gene and ∼6.9 kb upstream of cytoskeleton-associated protein 2-like (CKAP2L) gene. The IL1A gene encodes the IL1a protein, a member of the interleukin 1 cytokine family which is involved in various immune responses and inflammatory processes. These results provide important replication in an independent Japanese sample and, for the first time, association of the IL1A locus in endometriosis patients of European ancestry. SNPs within the IL1A locus may regulate other genes, but if IL1A is the target, our results provide supporting evidence for a link between inflammatory responses and the pathogenesis of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S)
The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.
To identify the optimal AUSDRISK threshold score to screen for pre‐diabetes and diabetes.
A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May ...and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre‐diabetes (5.7–6.4% or 39–47 mmol/mol), or normal (<5.7% or 39 mmol/mol).
Of these patients, 9 (2%) had undiagnosed diabetes and 60 (15%) had pre‐diabetes. A Receiver Operator Characteristic (ROC) curve was constructed to predict the presence of pre‐diabetes and diabetes; the area under the ROC curve was 0.72 (95%CI 0.65–0.78) indicating modest predictive ability. The optimal threshold cut point for AUSDRISK score was 17 (sensitivity 76%, specificity 61%, + likelihood ratio (LR) 1.96, ‐ likelihood ratio of 0.39) while the accepted cut point of 12 performed less well (sensitivity 94%, specificity 23%, +LR=1.22 ‐LR+0.26).
The AUSDRISK tool has the potential to be used as a screening tool for pre‐diabetes/diabetes in GP practices. A cut point of ≥17 would potentially identify 75% of all people at risk and three in 10 sent for further testing would be positive for prediabetes or diabetes.
Routine case‐finding in high‐risk patients will enable GPs to intervene early and prevent further public health burden from the sequelae of diabetes.
Total iron intake is not strongly associated with iron stores, but haem iron intake may be more predictive. Haem iron is not available in most nutrient databases, so experimentally determined haem ...contents were applied to an Australian Food Frequency Questionnaire (FFQ) to estimate haem iron intake in a representative sample of young women (25-30 years). The association between dietary haem iron intakes and incident self-reported diagnosed iron deficiency over six years of follow-up was examined. Haem iron contents for Australian red meats, fish, and poultry were applied to haem-containing foods in the Dietary Questionnaire for Epidemiological Studies V2 (DQESv2) FFQ. Haem iron intakes were calculated for 9076 women from the Australian Longitudinal Study on Women's Health (ALSWH) using the DQESv2 dietary data from 2003. Logistic regression was used to examine the association between haem iron intake (2003) and the incidence of iron deficiency in 2006 and 2009. Multiple logistic regression showed baseline haem iron intake was a statistically significant predictor of iron deficiency in 2006 (Odds Ratio (OR): 0.91; 95% Confidence Interval (CI): 0.84-0.99;
-value: 0.020) and 2009 (OR: 0.89; 95% CI: 0.82-0.99;
-value: 0.007). Using the energy-adjusted haem intake made little difference to the associations. Higher haem iron intake is associated with reduced odds of iron deficiency developing in young adult Australian women.
To determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and ...insulin sensitivity in the former 2 groups.
Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator.
A total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001). In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01) in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity.
Higher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.
Despite the increasing interest towards the biological role of L-ergothioneine, little is known about the serum concentrations of this unusual aminothiol in older adults. We addressed this issue in a ...representative sample of community-dwelling middle-aged and older adults.
Body mass index, estimated glomerular filtration rate, serum concentrations of L-ergothioneine, taurine, homocysteine, cysteine, glutathione, cysteinylglycine, and glutamylcysteine were evaluated in 439 subjects (age 55-85 years) randomly selected from the Hunter Community Study.
Median L-ergothioneine concentration in the entire cohort was 1.01 IQR 0.78-1.33 µmol/L. Concentrations were not affected by gender (P = 0.41) or by presence of chronic medical conditions (P = 0.15). By considering only healthy subjects, we defined a reference interval for L-ergothioneine serum concentrations from 0.36 (90% CI 0.31-0.44) to 3.08 (90% CI 2.45-3.76) µmol/L. Using stepwise multiple linear regression analysis L-ergothioneine was negatively correlated with age (rpartial = -0.15; P = 0.0018) and with glutamylcysteine concentrations (rpartial = -0.13; P = 0.0063).
A thorough analysis of serum L-ergothioneine concentrations was performed in a large group of community-dwelling middle-aged and older adults. Reference intervals were established. Age and glutamylcysteine were independently negatively associated with L-ergothioneine serum concentration.