Air pollution and diabetes association : modification by type 2 diabetes genetic risk score

Exposure to ambient air pollution (AP) exposure has been linked to type 2 diabetes (T2D) risk. Evidence on the impact of T2D genetic variants on AP susceptibility is lacking. Compared to single variants, joint genetic variants contribute substantially to disease risk. We investigated the modification of AP and diabetes association by a genetic risk score (GRS) covering 63 T2D genes in 1524 first follow-up participants of the Swiss cohort study on air pollution and lung and heart diseases in adults. Genome-wide data and covariates were available from a nested asthma case-control study design. AP was estimated as 10-year mean residential particulate matter <10μm (PM10). We computed count-GRS and weighted-GRS, and applied PM10 interaction terms in mixed logistic regressions, on odds of diabetes. Analyses were stratified by pathways of diabetes pathology and by asthma status. Diabetes prevalence was 4.6% and mean exposure to PM10 was 22μg/m(3). Odds of diabetes increased by 8% (95% confidence interval: 2, 14%) per T2D risk allele and by 35% (-8, 97%) per 10μg/m(3) exposure to PM10. We observed a positive interaction between PM10 and count-GRS on diabetes [ORinteraction=1.10 (1.01, 1.20)], associations being strongest among participants at the highest quartile of count-GRS [OR: 1.97 (1.00, 3.87)]. Stronger interactions were observed with variants of the GRS involved in insulin resistance [(ORinteraction=1.22 (1.00, 1.50)] than with variants related to beta-cell function. Interactions with count-GRS were stronger among asthma cases. We observed similar results with weighted-GRS. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity. These results need confirmation in diabetes cohort consortia

Prevalence of renal impairment and its association with cardiovascular risk factors in a general population: results of the Swiss SAPALDIA study

Background. Impaired renal function is evolving as an independent marker of the risk of cardiovascular morbidity and mortality. Little is known about the prevalence of impaired renal function and its relationship to cardiovascular risk factors in the Swiss general population. Methods. SAPALDIA comprises a random sample of the Swiss population established in 1991, originally to investigate the health effects of long-term exposure to air pollution. Participants were reassessed in 2002/3 and blood measurements were obtained (n = 6317). Renal function was estimated using the Cockcroft-Gault equation and the modified MDRD (four-component) equation incorporating age, race, gender and serum creatinine level. Results. The estimated prevalence of impaired renal function [estimated glomerular filtration rate <60 ml/min/1.73 m2] differed substantially between men and women, particularly at higher ages, and amounted to 13% [95% confidence interval (CI) 10-16%] and 36% (95% CI 32-40%) in men and women, respectively, of 65 years or older. Smoking, obesity, blood lipid levels, high systolic blood pressure and hyperuricaemia were all more common in men when compared with women. These cardiovascular risk factors were also associated independently with creatinine in both women and men. Women were less likely to receive cardiovascular drugs, in particular angiotensin-converting enzyme inhibitors and β-blockers, when compared with men of the same age. Conclusion. Moderate renal impairment seems to be prevalent in the general population, with an apparent excess in females which is not explained by conventional cardiovascular risk factors. The unexpected finding questions the validity of the prediction equations, in particular in female

Transportation Noise and Blood Pressure in a Population-Based Sample of Adults

Background: There is some evidence for an association between traffic noise and ischemic heart disease; however, associations with blood pressure have been inconsistent, and little is known about health effects of railway noise

Differences in Heart Rate Variability Associated with Long-Term Exposure to NO2

BACKGROUND: Heart rate variability (HRV), a measure of cardiac autonomic tone, has been associated with cardiovascular morbidity and mortality. Short-term studies have shown that subjects exposed to higher traffic-associated air pollutant levels have lower HRV. OBJECTIVE: Our objective was to investigate the effect of long-term exposure to nitrogen dioxide on HRV in the Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). METHODS: We recorded 24-hr electrocardiograms in randomly selected SAPALDIA participants >or= 50 years of age. Other examinations included an interview investigating health status and measurements of blood pressure, body height, and weight. Annual exposure to NO2 at the address of residence was predicted by hybrid models (i.e., a combination of dispersion predictions, land-use, and meteorologic parameters). We estimated the association between NO2 and HRV in multivariable linear regression models. Complete data for analyses were available for 1,408 subjects. RESULTS: For women, but not for men, each 10-microg/m3 increment in 1-year averaged NO2 level was associated with a decrement of 3% (95% CI, -4 to -1) for the standard deviation of all normal-to-normal RR intervals (SDNN), -6% (95% CI, -11 to -1) for nighttime low frequency (LF), and -5% (95% CI, -9 to 0) for nighttime LF/high-frequency (HF) ratio. We saw no significant effect for 24-hr total power (TP), HF, LF, or LF/HF or for nighttime SDNN, TP, or HF. In subjects with self-reported cardiovascular problems, SDNN decreased by 4% (95% CI, -8 to -1) per 10-microg/m3 increase in NO2. CONCLUSIONS: There is some evidence that long-term exposure to NO2 is associated with cardiac autonomic dysfunction in elderly women and in subjects with cardiovascular disease

Long-term exposure to ambient air pollution and metabolic syndrome in adults

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

A common functional variant on the pro-inflammatory Interleukin-6 gene may modify the association between long-term PM10 exposure and diabetes

Air pollutants have been linked to type 2 diabetes (T2D), hypothesized to act through inflammatory pathways and may induce interleukin-6 gene (IL6) in the airway epithelium. The cytokine interleukin-6 may impact on glucose homeostasis. Recent meta-analyses showed the common polymorphisms, IL6 -572G &gt; C and IL6 -174G &gt; C to be associated with T2D risk. These IL6 variants also influence circulatory interleukin-6 levels. We hypothesize that these common functional variants may modify the association between air pollutants and T2D.; We cross-sectionally studied 4410 first follow-up participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases (SAPALDIA), aged 29 to 73 years who had complete data on genotypes, diabetes status and covariates. We defined diabetes as self-reported physician-diagnosed, or use of diabetes medication or non-fasting glucose &gt;11.1 mmol/L or HbA1c &gt; 0.065. Air pollution exposure was 10-year mean particulate matter &lt;10 μm in diameter (PM10) assigned to participants' residences using a combination of dispersion modelling, annual trends at monitoring stations and residential history. We derived interaction terms between PM10 and genotypes, and applied mixed logistic models to explore genetic interactions by IL6 polymorphisms on the odds of diabetes.; There were 252 diabetes cases. Respective minor allele frequencies of IL6 -572G &gt; C and IL6 -174G &gt; C were 7 and 39 %. Mean exposure to PM10 was 22 μg/m(3). Both variants were not associated with diabetes in our study. We observed a significant positive association between PM10 and diabetes among homozygous carriers of the pro-inflammatory major G-allele of IL6 -572G &gt; C [Odds ratio: 1.53; 95 % confidence interval (1.22, 1.92); P interaction (additive) = 0.003 and P interaction (recessive) = 0.006]. Carriers of the major G-allele of IL6 -174G &gt; C also had significantly increased odds of diabetes, but interactions were statistically non-significant.; Our results on the interaction of PM10 with functionally well described polymorphisms in an important pro-inflammatory candidate gene are consistent with the hypothesis that air pollutants impact on T2D through inflammatory pathways. Our findings, if confirmed, are of high public health relevance considering the ubiquity of the major G allele, which puts a substantial proportion of the population at risk for the development of diabetes as a result of long-term exposure to air pollution

How Many Responses Do We Need? Using Generalizability Analysis to Estimate Minimum Necessary Response Rates for Online Student Evaluations

Construct:The study compares paper and online ratings of instructional units and analyses, with the G-study using the symmetry principle, the response rates needed to ensure acceptable precision of the measure when compliance is low. Background: Students' ratings of teaching contribute to the quality of medical training programs. To date, many schools have replaced pen-and-paper questionnaires with electronic forms, despite the lower response rates consistently reported with the latter. Few available studies have examined the effects of low response rates on the reliability and precision of the evaluation measure. Moreover, the minimum number of raters to target when response rates are low remains unclear. Approach: Descriptive data were derived from 799 students' paper and online ratings of 11 preclinical instructional units (PIUs). Reliability was assessed by Cronbach's alpha coefficients. The generalizability method applying the symmetry principle approach was used to analyze the precision of the measure with a reference standard error of mean (SEM) set at 0.10; optimization models were built to estimate minimum response rates. Results: Overall, response rates were 74% and 30% (p < .001) and PIUs ratings were 3.8 ± 0.5 and 3.6 ± 0.5 (p = .02), respectively in paper and online questionnaires. Higher SEM levels and significantly larger 95% confidence intervals of PIUs rating scores were observed with online evaluations. To keep the SEM within preset limits of precision, a minimum of 48% response rate was estimated for online formats. Conclusions: The proposed generalizability analysis allowed estimating the minimum response needed to maintain acceptable precision in online evaluations. The effects of response rates on accuracy are discussed

SERPINA1 PiZ and PiS heterozygotes and lung function decline in the SAPALDIA cohort

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency is a strong risk factor for COPD. But the impact of gene variants resulting in mild or intermediate AAT deficiency on the longitudinal course of respiratory health remains controversial. There is indication from experimental studies that pro-inflammatory agents like cigarette smoke can interact with these variants and thus increase the risk of adverse respiratory health effects. Therefore, we tested the effect of the presence of a protease inhibitor (Pi) S or Z allele (PiMS and PiMZ) on the change in lung function in different inflammation-exposed subgroups of a large, population-based cohort study.METHODOLOGY AND PRINCIPAL FINDINGS: The SAPALDIA population includes over 4600 subjects from whom SERPINA1 genotypes for S and Z alleles, spirometry and respiratory symptoms at baseline and after 11 years follow-up, as well as proxies for inflammatory conditions, such as detailed smoking history, obesity and high sensitivity C-reactive protein (hs-CRP), were available. All analyses were performed by applying multivariate regression models. There was no overall unfavourable effect of PiMS or PiMZ genotype on lung function change. We found indication that PiZ heterozygosity interacted with inflammatory stimuli leading to an accelerated decline in measures in use as indices for assessing mild airway obstruction. Obese individuals with genotype PiMM had an average annual decline in the forced mid expiratory flow (?FEF25-75%) of 58.4 ml whereas in obese individuals with PiMZ it amounted to 92.2 ml (p?=?0.03). Corresponding numbers for persistent smokers differed even more strongly (66.8 ml (PiMM) vs. 108.2 ml (PiMZ), p?=?0.005). Equivalent, but less strong associations were observed for the change in the FEV1/FVC ratio. CONCLUSIONS: We suggest that, in addition to the well established impact of the rare PiZZ genotype, one Z allele may be sufficient to accelerate lung function decline in population subgroups characterized by elevated levels of low grade inflammation

Impact of road traffic noise annoyance on health-related quality of life : results from a population-based study

PURPOSE: To estimate the impact of traffic-related noise annoyance on health-related quality of life (HrQoL) in a population-based study and potential effect modification by gender. METHODS: The study included 5,021 participants of the Swiss Cohort Study of Air Pollution and Lung Disease in Adults second survey. The association between traffic-related noise annoyance, measured on an 11-point scale, and HrQoL, based on SF-36 scores, was investigated by multivariate regression analysis. Effect sizes were calculated, and interactions by gender and chronic disease status examined. RESULTS: Thirteen percentage of the study population reported high annoyance due to traffic. Women were more likely to report high noise annoyance (adjOR 1.23; 95%CI 1.01-1.48). Except for general health, all SF-36 scores showed a significant negative association with noise annoyance. The respective effect sizes ranged between 0.13 and 0.54. Significant effect modification by gender and chronic disease status was present in specific SF-36 domains. CONCLUSION: This paper presents first evidence of an inverse relationship of noise annoyance and HrQoL in a general population. Although the estimated effects are small to moderate for individuals, they may add up to a relevant public health impact