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Air pollution represents a serious threat to health on a global scale, being responsible for a large portion of the global burden of disease from environmental factors. Current evidence about the association between air pollution exposure and Diabetes Mellitus (DM) is still controversial. We aimed to evaluate the association between area-level ambient air pollution and self-reported DM in a large population sample in Italy.
Materials and methods
We extracted information about self-reported and physician diagnosed DM, risk factors and socio-economic status from 12 surveys conducted nationwide between 1999 and 2013. We obtained annual averaged air pollution levels for the years 2003, 2005, 2007 and 2010 from the AMS-MINNI national integrated model, which simulates the dispersion and transformation of pollutants. The original maps, with a resolution of 4 x 4 km2, were normalized and aggregated at the municipality class of each Italian region, in order to match the survey data. We fit logistic regression models with a hierarchical structure to estimate the relationship between PM10, PM2.5, NO2 and O3 four-years mean levels and the risk of being affected by DM.
We included 376,157 individuals aged more than 45 years. There were 39,969 cases of DM, with an average regional prevalence of 9.8% and a positive geographical North-to-South gradient, opposite to that of pollutants’ concentrations. For each 10 μg/m3 increase, the resulting ORs were 1.04 (95% CI 1.01-1.07) for PM10, 1.04 (95% CI 1.02-1.07) for PM2.5, 1.03 (95% CI 1.01-1.05) for NO2 and 1.06 (95% CI 1.01-1.11) for O3, after accounting for relevant individual risk factors. The associations were robust to adjustment for other pollutants in two-pollutant models tested (ozone plus each other pollutant).
We observed a significant positive association between each examined pollutant and prevalent DM. Risk estimates were consistent with current evidence, and robust to sensitivity analysis. Our study adds evidence about the effects of air pollution on diabetes and suggests a possible role of ozone as an independent factor associated with the development of DM. Such relationship is of great interest for public health and deserves further investigation.
Association between PM10, PM2.5, NO2, O3 and self-reported diabetes in Italy: A cross-sectional, ecological study
Riccardo Orioli, Conceptualization, Data curation, Formal analysis, Investigation, Writing - original draft,1,* Giuseppe Cremona, Data curation, Visualization, Writing - original draft,2 Luisella Ciancarella, Supervision, Writing - review & editing,2 and Angelo G. Solimini, Conceptualization, Data curation, Formal analysis, Methodology, Supervision, Writing - review & editing1 Roger A. Coulombe, Editor
To analyze the frequency and associations with prognostic markers and outcome of mutations in IDH genes encoding isocitrate dehydrogenases in adult de novo cytogenetically normal acute myeloid leukemia (CN-AML).
Patients and Methods
Diagnostic bone marrow or blood samples from 358 patients were analyzed for IDH1 and IDH2 mutations by DNA polymerase chain reaction amplification/sequencing. FLT3, NPM1, CEBPA, WT1, and MLL mutational analyses and gene- and microRNA-expression profiling were performed centrally.
IDH mutations were found in 33% of the patients. IDH1 mutations were detected in 49 patients (14%; 47 with R132). IDH2 mutations, previously unreported in AML, were detected in 69 patients (19%; 13 with R172 and 56 with R140). R172 IDH2 mutations were mutually exclusive with all other prognostic mutations analyzed. Younger age (< 60 years), molecular low-risk (NPM1-mutated/FLT3-internal tandem duplication-negative) IDH1-mutated patients had shorter disease-free survival than molecular low-risk IDH1/IDH2-wild-type (wt) patients (P = .046). R172 IDH2-mutated patients had lower complete remission rates than IDH1/IDH2wt patients (P = .007). Distinctive microarray gene- and microRNA-expression profiles accurately predicted R172 IDH2 mutations. The highest expressed gene and microRNAs in R172 IDH2-mutated patients compared with the IDH1/IDH2wt patients were APP (previously associated with complex karyotype AML) and miR-1 and miR-133 (involved in embryonal stem-cell differentiation), respectively. Conclusion IDH1 and IDH2 mutations are recurrent in CN-AML and have an unfavorable impact on outcome. The R172 IDH2 mutations, previously unreported in AML, characterize a novel subset of CN-AML patients lacking other prognostic mutations and associate with unique gene- and microRNA-expression profiles that may lead to the discovery of novel, therapeutically targetable leukemogenic mechanisms.
IDH1 and IDH2 Gene Mutations Identify Novel Molecular Subsets Within De Novo Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
Guido Marcucci, Kati Maharry, Yue-Zhong Wu, Michael D. Radmacher, Krzysztof Mrozek, Dean Margeson, Kelsi B. Holland, Susan P. Whitman, Heiko Becker, Sebastian Schwind, Klaus H. Metzeler, Bayard L. Powell, Thomas H. Carter, Jonathan E. Kolitz, Meir Wetzler, Andrew J. Carroll, Maria R. Baer, Michael A. Caligiuri, Richard A. Larson, and Clara D. Bloomfield
2010 May 10