Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: a national toxicology program workshop review

Abstract

Background: Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health.

Objective: We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs) and type 2 diabetes.

Methods: Using a PubMed search and reference lists from relevant studies or review articles, we identified 72 epidemiological studies that investigated associations of persistent organic pollutants (POPs) with diabetes. We evaluated these studies for consistency, strengths and weaknesses of study design (including power and statistical methods), clinical diagnosis, exposure assessment, study population characteristics, and identification of data gaps and areas for future research.

Conclusions: Heterogeneity of the studies precluded conducting a meta-analysis, but the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes. Collectively, these data are not sufficient to establish causality. Initial data mining revealed that the strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals. There is less indication of an association between other nonorganochlorine POPs, such as perfluoroalkyl acids and brominated compounds, and type 2 diabetes. Experimental data are needed to confirm the causality of these POPs, which will shed new light on the pathogenesis of diabetes. This new information should be considered by governmental bodies involved in the regulation of environmental contaminants.

Figure 1

Associations between trans-nonachlor and diabetes in epidemiological studies. Abbreviations: %ile, percentile; Adj, adjusted; CARDIA, Coronary Artery Risk Development in Young Adults; CS, cross-sectional; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; HHANES, Hispanic Health and Nutrition Examination Survey; NCC, nested case–control; ND, not determined; NHANES, National Health and Nutrition Examination Survey; Q, quartile; std, standardized; T, tertile; ww, wet weight. Self-report indicates a self-reported diagnosis of T2D; medication refers to medications used to treat T2D; and FBG and HbA1c indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted; all exposures were measured in serum samples.

Figure 2

Association between DDE, DDT, or DDD and diabetes in epidemiological studies. Abbreviations: %ile, percentile; Adj, adjusted; CARDIA, Coronary Artery Risk Development in Young Adults; CS, cross-sectional; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; HHANES, Hispanic Health and Nutrition Examination Survey; IRR, incidence rate ratio; ND, not determined; NCC, nested case–control; NHANES, National Health and Nutrition Examination Survey; OGTT, oral glucose tolerance test; Q, quartile; QU, quintile; std, standardized; T, tertile; ww, wet weight. Self report indicates self-reported diagnosis of T2D; medication refers to medications used to treat T2D; and OGTT, FBG, and HbA1c indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted; all exposures were measured in serum samples.

Figure 3

Association between PCBs and diabetes in epidemiological studies. Abbreviations: %ile, percentile; Adj, adjusted; CARDIA, Coronary Artery Risk Development in Young Adults; CS, cross-sectional; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; IDR, incidence density ratio; IRR, incidence rate ratio; ND, not determined; OGTT, oral glucose tolerance test; Q, quartile; T, tertile; WHILA, Women’s Health in the Lund Area. Self-report indicates self-reported diagnosis of T2D; medication refers to medications used to treat T2D; and OGTT, FBG, and HbA1c indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted; exposures were measured in serum samples unless otherwise indicated.

Figure 4

Association between Agent Orange or dioxin and diabetes in studies of Vietnam veterans. Abbreviations: Adj, adjusted; AFHS ORH, Air Force Health Study, Operation Ranch Hand; FBG, fasting blood glucose; OGTT, oral glucose tolerance test; Phys dx, physcian diagnosis; HR, hazard ratio; RR, relative risk; Q, quartile; OGTT and FBG indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted.

Figure 5

Association between miscellaneous organochlorine POPs and diabetes in epidemiological studies. Abbreviations: %ile, percentile; Adj, adjusted; AFHS ORH, Air Force Health Study, Operation Ranch Hand; avg, average; CARDIA, Coronary Artery Risk Development in Young Adults; CS, cross-sectional; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; HHANES, Hispanic Health and Nutrition Examination Survey; I‑TEQ, international toxic equivalent; med exam, medical exam; NCC, nested case–control; ND, not determined; NHANES, National Health and Nutrition Examination Survey; OGTT, oral glucose tolerance test; Phys dx, physician diagnosis; PIVUS, Prospective Investigation of the Vasculature in Uppsala Seniors; Q, quartile; QU, quintile; RR, relative risk; std, standardized; T, tertile; TEQ, toxic equivalents; ww, wet weight. Self-report indicates self-reported diagnosis of T2D; medication refers to medications used to treat T2D; and OGTT, FBG, and HbA1c indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted; exposures were measured in serum samples unless otherwise indicated.

Figure 6

Association between POPs mixtures and diabetes in epidemiological studies. Abbreviations: %ile, percentile; Adj, adjusted; CARDIA, Coronary Artery Risk Development in Young Adults; CC, case–control; CS, cross-sectional; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; IRR, incidence rate ratio; NHANES, National Health and Nutrition Examination Survey; OGTT, oral glucose tolerance test; Q, quartile; QU, quintile; T, tertile. Self-report indicates self-reported diagnosis of T2D; medication refers to medications used to treat T2D; and OGTT, FBG, and HbA1c indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted.

Figure 7

Association between brominated compounds and diabetes in epidemiological studies. Abbreviations: %ile, percentile; Adj, adjusted; CARDIA, Coronary Artery Risk Development in Young Adults; CC, case–control; CS, cross-sectional; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; IDR, incidence density ratio; ND, not determined; NHANES, National Health and Nutrition Examination Survey; Q, quartile. Self-report indicates self-reported diagnosis of T2D; medication refers to medications used to treat T2D; and FBG and HbA1c indicate levels that were sufficiently elevated to be classified as T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted; all exposures were measured in serum samples.

Figure 8

Association between perfluoro­alkyl acids and diabetes in epidemiological studies. Abbreviations: Adj, adjusted; C8 Health, C8 Health Project; CS, cross-sectional; FBG, fasting blood glucose; NHANES, National Health and Nutrition Examination Survey; PFHS, perfluoro­hexane sulfonate; PFNA, perfluoro­nonanoic acid; Q, quartile. Self-report indicates self-reported diagnosis of T2D. ^aValues are adjusted ORs unless otherwise noted. ^bIf no lipid adjustments were reported, the OR was not lipid adjusted; all exposures were measured in serum samples.