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      Obesity and the relation between joint exposure to ambient air pollutants and incident type 2 diabetes: A cohort study in UK Biobank

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          Abstract

          Background

          Air pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship.

          Methods and findings

          A total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m 2. Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM 2.5), between 2.5 μm and 10 μm (PM 2.5–10), nitrogen dioxide (NO 2), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D ( p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants.

          Conclusions

          We found that various air pollutants PM 2.5, PM 2.5–10, NO 2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.

          Abstract

          Xiang Li and co-workers study the potential influence of obesity on associations between air pollutants and incidence of type 2 diabetes.

          Author summary

          Why was this study done?
          • Recent evidence has linked ambient air pollution with type 2 diabetes (T2D). However, most of them were mainly focused on 1 or 2 air pollutants separately. In addition, it has been reported that the association between air pollution and T2D was augmented among people with increased adiposity.

          • Individuals are usually exposed to various air pollutants simultaneously; and the importance of assessing multi-air pollutant exposures as a whole has been increasingly recognized.

          • Thus, in this study, we aimed to analyze the association between the air pollution score that incorporates various air pollutants with the risk of T2D. We also particularly examined the potential modification by obesity.

          What did the researchers do and find?
          • We built an air pollution score, incorporating PM 2.5, PM 2.5–10, nitrogen dioxide (NO 2), and nitric oxide (NO), and analyzed its association with the risk of T2D among 449,006 participants from UK Biobank. Air pollutants were measured in 2010. During a median follow-up time of 11 years, 18,239 T2D cases were documented.

          • We found that long-term exposure to various air pollutants, individually or jointly, was associated with an increased risk of T2D. Moreover, such association was more pronounced among people with increased adiposity.

          What do these findings mean?
          • Our findings highlight the importance of comprehensively assessing various air pollutants as a whole in the prevention of T2D.

          • Given the adverse impact of air pollution on T2D, attention should be paid to reducing and mitigating air pollution.

          • Our results also emphasize the merit of obesity management.

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          Most cited references55

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          International physical activity questionnaire: 12-country reliability and validity.

          Physical inactivity is a global concern, but diverse physical activity measures in use prevent international comparisons. The International Physical Activity Questionnaire (IPAQ) was developed as an instrument for cross-national monitoring of physical activity and inactivity. Between 1997 and 1998, an International Consensus Group developed four long and four short forms of the IPAQ instruments (administered by telephone interview or self-administration, with two alternate reference periods, either the "last 7 d" or a "usual week" of recalled physical activity). During 2000, 14 centers from 12 countries collected reliability and/or validity data on at least two of the eight IPAQ instruments. Test-retest repeatability was assessed within the same week. Concurrent (inter-method) validity was assessed at the same administration, and criterion IPAQ validity was assessed against the CSA (now MTI) accelerometer. Spearman's correlation coefficients are reported, based on the total reported physical activity. Overall, the IPAQ questionnaires produced repeatable data (Spearman's rho clustered around 0.8), with comparable data from short and long forms. Criterion validity had a median rho of about 0.30, which was comparable to most other self-report validation studies. The "usual week" and "last 7 d" reference periods performed similarly, and the reliability of telephone administration was similar to the self-administered mode. The IPAQ instruments have acceptable measurement properties, at least as good as other established self-reports. Considering the diverse samples in this study, IPAQ has reasonable measurement properties for monitoring population levels of physical activity among 18- to 65-yr-old adults in diverse settings. The short IPAQ form "last 7 d recall" is recommended for national monitoring and the long form for research requiring more detailed assessment.
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            UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

            Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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              Genetic studies of body mass index yield new insights for obesity biology.

              Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P  20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                30 August 2021
                August 2021
                : 18
                : 8
                : e1003767
                Affiliations
                [1 ] Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, United States of America
                [2 ] Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
                [3 ] School of Design and the Built Environment, Curtin University, Bentley, Perth, Western Australia, Australia
                [4 ] Department of Epidemiology and Biostatistics, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China
                [5 ] Department of Obstetrics, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
                [6 ] Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
                Monash University, AUSTRALIA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-6637-6428
                https://orcid.org/0000-0003-3420-9622
                https://orcid.org/0000-0002-8041-7791
                Article
                PMEDICINE-D-21-01221
                10.1371/journal.pmed.1003767
                8439461
                34460827
                b2548899-ba78-4098-a148-1e558434479b
                © 2021 Li et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 March 2021
                : 13 August 2021
                Page count
                Figures: 2, Tables: 3, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: HL071981, HL034594, HL126024
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: DK115679, DK091718, DK100383
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000061, Fogarty International Center;
                Award ID: TW010790
                Award Recipient :
                Funded by: Tulane Research Centers of Excellence Awards
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000968, American Heart Association;
                Award ID: 19PRE34380036
                Award Recipient :
                LQ received awards from National Heart, Lung, and Blood Institute (Award # HL071981, HL034594, HL126024, URL: https://www.nhlbi.nih.gov/); the National Institute of Diabetes and Digestive and Kidney Diseases (Awards # DK115679, DK091718, DK100383, URL: https://www.niddk.nih.gov/), the Fogarty International Center (award # TW010790, URL: https://www.fic.nih.gov/), and Tulane Research Centers of Excellence Awards (URL: https://sph.tulane.edu/). XL received award from the American Heart Associatioion (award #: 19PRE34380036; URL: https://professional.heart.org/en/research-programs/application-information/predoctoral-fellowship). The funders have no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Ecology and Environmental Sciences
                Pollution
                Air Pollution
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Type 2 Diabetes Risk
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Type 2 Diabetes Risk
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Biology and Life Sciences
                Biochemistry
                Neurochemistry
                Neurochemicals
                Nitric Oxide
                Biology and Life Sciences
                Neuroscience
                Neurochemistry
                Neurochemicals
                Nitric Oxide
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Activity
                Custom metadata
                vor-update-to-uncorrected-proof
                2021-09-14
                Requests to access the dataset from qualified researchers trained in human participants confidentiality protocols may be sent to UK Biobank ( https://www.ukbiobank.ac.uk/researchers/). The current study has been conducted using the UK Biobank Resource under Application 29256.

                Medicine
                Medicine

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