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      Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans

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          Abstract

          OBJECTIVE

          Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels.

          RESEARCH DESIGN AND METHODS

          Participants were selected from BetaGene ( n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO 2, O 3, and PM 2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NO x. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits.

          RESULTS

          Short-term (up to 58 days cumulative lagged averages) exposure to PM 2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM 2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C ( P ≤ 0.043). The effects of short-term PM 2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes.

          CONCLUSIONS

          Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae.

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          Most cited references29

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          Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.

          Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
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            Measuring Adiposity in Patients: The Utility of Body Mass Index (BMI), Percent Body Fat, and Leptin

            Background Obesity is a serious disease that is associated with an increased risk of diabetes, hypertension, heart disease, stroke, and cancer, among other diseases. The United States Centers for Disease Control and Prevention (CDC) estimates a 20% obesity rate in the 50 states, with 12 states having rates of over 30%. Currently, the body mass index (BMI) is most commonly used to determine adiposity. However, BMI presents as an inaccurate obesity classification method that underestimates the epidemic and contributes to failed treatment. In this study, we examine the effectiveness of precise biomarkers and duel-energy x-ray absorptiometry (DXA) to help diagnose and treat obesity. Methodology/Principal Findings A cross-sectional study of adults with BMI, DXA, fasting leptin and insulin results were measured from 1998–2009. Of the participants, 63% were females, 37% were males, 75% white, with a mean age = 51.4 (SD = 14.2). Mean BMI was 27.3 (SD = 5.9) and mean percent body fat was 31.3% (SD = 9.3). BMI characterized 26% of the subjects as obese, while DXA indicated that 64% of them were obese. 39% of the subjects were classified as non-obese by BMI, but were found to be obese by DXA. BMI misclassified 25% men and 48% women. Meanwhile, a strong relationship was demonstrated between increased leptin and increased body fat. Conclusions/Significance Our results demonstrate the prevalence of false-negative BMIs, increased misclassifications in women of advancing age, and the reliability of gender-specific revised BMI cutoffs. BMI underestimates obesity prevalence, especially in women with high leptin levels (>30 ng/mL). Clinicians can use leptin-revised levels to enhance the accuracy of BMI estimates of percentage body fat when DXA is unavailable.
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              Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.

              Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%). At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                April 2016
                11 February 2016
                : 39
                : 4
                : 547-554
                Affiliations
                [1] 1Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA
                [2] 2Department of Psychiatry, Kern Medical Center, Bakersfield, CA
                [3] 3Department of Public Health, California State University, Los Angeles, CA
                [4] 4Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA
                [5] 5Department of Physiology and Biophysics, Keck School of Medicine of the University of Southern California, Los Angeles, CA
                [6] 6Diabetes and Obesity Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA
                [7] 7Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
                [8] 8Division of Diabetes and Endocrinology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA
                [9] 9Sonoma Technology, Inc., Petaluma, CA
                [10] 10Spatial Sciences Institute, University of Southern California, Los Angeles, CA
                Author notes
                Corresponding author: Frank D. Gilliland, gillilan@ 123456usc.edu .
                Article
                1795
                10.2337/dc15-1795
                4806768
                26868440
                9f9351c6-9cb4-4fdb-a7b3-9c7e067b9209
                © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
                History
                : 17 August 2015
                : 4 January 2016
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 38, Pages: 8
                Funding
                Funded by: National Institutes of Health http://dx.doi.org/10.13039/100000002
                Award ID: DK-061628
                Award ID: M01-RR-0043
                Award ID: UL1-TR000130
                Funded by: American Diabetes Association http://dx.doi.org/10.13039/100000041
                Award ID: 7-09-CT-09
                Funded by: National Institute of Environmental Health Sciences http://dx.doi.org/10.13039/100000066
                Award ID: 5P30ES007048
                Award ID: 5P01ES011627
                Funded by: Hastings Foundation
                Categories
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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