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Association of Bisphenol A With Diabetes and Other Abnormalities

Association of Bisphenol A With Diabetes and Other Abnormalities To the Editor: From a cross-sectional analysis of urinary chemical concentrations and health status in the general US adult population, Dr Lang and colleagues1 reported that BPA was associated with cardiovascular diagnoses, diabetes, and abnormal liver enzyme concentrations. However, the potential for false positives, briefly mentioned but not analyzed, is substantial when the complete Centers for Disease Control and Prevention (CDC) design is examined. The CDC NHANES (2003-2004)2,3 measured 275 environmental chemicals and a wide range of health outcomes. Although the study by Lang et al focused on 1 chemical and 16 health outcomes (8 patient-reported medical outcomes and 8 clinical chemistry measurements), counting to determine how many questions were at issue and in how many ways these questions can be statistically analyzed is important. Focusing only on the health outcomes selected by the authors, the analysis forms a 16 × 275 composite set of questions. However, there are more than 8 ways that the medical outcomes can be examined since 2 of the outcomes have subgroups, any 1 or combination of which could result in an association. Likewise, there are more than 8 ways the clinical measurements can be examined because additional measurements and derived outcomes were reported. Overall, we counted 32 possible outcomes. From the perspective of the complete CDC study design, there are 32 × 275 = 8800 questions at issue. In addition, there is a large list of possible confounder variables; we counted 10. The authors used 2 regression models to adjust for confounders, but with 10 confounders, there are 1024 possible different adjustment models. Considering the complete list of questions at issue and confounders, the model space could be as large as approximately 9 million models. Given the number of questions at issue and possible modeling variations in the CDC design, the findings reported by the authors could well be the result of chance. The authors acknowledged as much for only 16 questions for BPA alone, and we amplify their warning by pointing out the conceptually much larger CDC grand design. There could easily be a flood of articles reporting chance results. We note that JAMA recently published an article reporting an association between arsenic and diabetes using the same database.4 We think it is a good time to step back and consider the entire CDC study for the large, planned study that it is and develop a statistical analysis strategy that takes into account the large number of questions at issue. Back to top Article Information Financial Disclosures: None reported. References 1. Lang IA, Galloway TS, Scarlett A, et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008;300(11):1303-131018799442PubMedGoogle ScholarCrossref 2. Centers for Disease Control and Prevention (CDC). National Health and Nutrition Examination Survey Data 2003-04. Hyattsville, MD: US Dept of Health and Human Services; 2004 3. Centers for Disease Control and Prevention (CDC). Third National Report on Human Exposure to Environmental Chemicals. Atlanta, GA: CDC; 2005 4. Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E. Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA. 2008;300(7):814-82218714061PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Association of Bisphenol A With Diabetes and Other Abnormalities

Young, S. Stanley; Yu, Min
JAMA , Volume 301 (7) – Feb 18, 2009
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References (4)

Publisher
American Medical Association
Copyright
Copyright © 2009 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2009.122
Publisher site
See Article on Publisher Site

Abstract

To the Editor: From a cross-sectional analysis of urinary chemical concentrations and health status in the general US adult population, Dr Lang and colleagues1 reported that BPA was associated with cardiovascular diagnoses, diabetes, and abnormal liver enzyme concentrations. However, the potential for false positives, briefly mentioned but not analyzed, is substantial when the complete Centers for Disease Control and Prevention (CDC) design is examined. The CDC NHANES (2003-2004)2,3 measured 275 environmental chemicals and a wide range of health outcomes. Although the study by Lang et al focused on 1 chemical and 16 health outcomes (8 patient-reported medical outcomes and 8 clinical chemistry measurements), counting to determine how many questions were at issue and in how many ways these questions can be statistically analyzed is important. Focusing only on the health outcomes selected by the authors, the analysis forms a 16 × 275 composite set of questions. However, there are more than 8 ways that the medical outcomes can be examined since 2 of the outcomes have subgroups, any 1 or combination of which could result in an association. Likewise, there are more than 8 ways the clinical measurements can be examined because additional measurements and derived outcomes were reported. Overall, we counted 32 possible outcomes. From the perspective of the complete CDC study design, there are 32 × 275 = 8800 questions at issue. In addition, there is a large list of possible confounder variables; we counted 10. The authors used 2 regression models to adjust for confounders, but with 10 confounders, there are 1024 possible different adjustment models. Considering the complete list of questions at issue and confounders, the model space could be as large as approximately 9 million models. Given the number of questions at issue and possible modeling variations in the CDC design, the findings reported by the authors could well be the result of chance. The authors acknowledged as much for only 16 questions for BPA alone, and we amplify their warning by pointing out the conceptually much larger CDC grand design. There could easily be a flood of articles reporting chance results. We note that JAMA recently published an article reporting an association between arsenic and diabetes using the same database.4 We think it is a good time to step back and consider the entire CDC study for the large, planned study that it is and develop a statistical analysis strategy that takes into account the large number of questions at issue. Back to top Article Information Financial Disclosures: None reported. References 1. Lang IA, Galloway TS, Scarlett A, et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008;300(11):1303-131018799442PubMedGoogle ScholarCrossref 2. Centers for Disease Control and Prevention (CDC). National Health and Nutrition Examination Survey Data 2003-04. Hyattsville, MD: US Dept of Health and Human Services; 2004 3. Centers for Disease Control and Prevention (CDC). Third National Report on Human Exposure to Environmental Chemicals. Atlanta, GA: CDC; 2005 4. Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E. Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA. 2008;300(7):814-82218714061PubMedGoogle ScholarCrossref

Journal

JAMA – American Medical Association

Published: Feb 18, 2009

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