Introduction
- POPs: Persistent organic pollutants (POPs) are a group of chemicals with common properties such as persistence, lipophilicity, and biomagnification in the food chain.
- Serum concentrations of POPs were strongly associated with the prevalence of type 2 diabetes in the U.S. general population; this association was stronger among obese persons than among nonobese persons.
- Organochlorine (OC) pesticides and polychlorinated biphenyl (PCB) congeners, not dioxins, were strongly associated with type 2 diabetes.
- POPs concentrations were very low, prevalent type 2 diabetes was rare even among obese persons.
- The decreasing trend of OC POPs during recent decades (Needham et al. 2005) is inconsistent with the current trend toward an increased prevalence of type 2 diabetes.
Materials and Methods
Source population
- CARDIA (Coronary Artery Risk Development in Young Adults) cohort: participants who were 18–30 years old with cardiovascular disease risk. 5,115 African-American and white participants were recruited at baseline in 1985–1986 (year 0); follow-up examinations were completed at years 2, 5, 7, 10, 15, and 20 (2005–2006) for 91%, 86%, 81%, 79%, 74%, and 72%, respectively, of survivors.
- Diabetes was defined as ever having taken antidiabetic medications or ever having had fasting glucose ≥ 126 mg/dL at two or more examinations.
- The National Health and Examination Survey (NHANES) 2003-2004 was used to compare serum concentrations of POPs between CARDIA subjects and current concentrations in the U.S. general population.
Statistical methods
- Lipid-standardized concentrations, the concentrations of serum POPs divided by total serum lipid content (milli- grams per deciliter) calculated as 2.2 × serum cholesterol (milligrams per deciliter) + serum triglycerides (milligrams per deciliter) + 62.3
- Lipid-standardized concentration has been regarded as better reflecting body burden than wet-weight concentrations.
- 31 POPs examined in the current study
- 8 POPs (trans-nonachlor, oxychlordane, PCB74, PCB153, PCB170, PCB180, PCB187, and BB153)
- Underlying biologic mechanisms that were suggested by others.
- In the summary analyses, we summed the individual ranks of several POPs.
- ORs (95% CIs) for the risk of type 2 diabetes
- Confounders: age (continuous), sex, race, BMI (continuous) - wet weights; triglycerides (continuous), total cholesterol (continuous) - lipid-adjusted analyses
Results
- The second quartile POPs concentrations in the current population were similar to those in the highest quartile in the NHANES subjects.
- Most PBDEs were not detectable in CARDIA subjects, whereas PBDEs were detectable in NHANES subjects, suggesting recent exposure to PBDEs.
- Some individual POPs displayed statistically significantly higher ORs of diabetes in the second quartile compared with the first quartile, particularly before lipid adjustment.
- The results for individual POPs should be carefully interpreted with regard to effects of lipid adjustment, because POPs may promote dyslipidemia (so the lipid adjustment could be an overadjustment).
- Among 8 OC pesticides, trans-nonachlor showed the strongest association with the risk of future diabetes.
- Highly chlorinated PCBs tended to show the highest risk in the second quartile with adjusted ORs of 2–3.
- For all 31 POPs, the increased risk in the highest sextile disappeared after lipid adjustment.
- Phenobarbital-type inducers and weak or non- inducers of CYP 450 showed low-dose effects, whereas mixed-type inducers did not show any association.
Discussion
The inverted U-shaped associations have been proposed as possible biological responses of endocrine disruptors, unlike the traditional paradigm of cellular toxicity in which there is a linear dose–response relation. POPs are well-known endocrine disruptors. Hormones act indirectly through binding to specific receptors. At present, there is little knowledge about the biological mechanisms that might link POPs and type 2 diabetes.
In general, serum concentrations of POPs tend to be highly correlated with each other because of the simultaneous exposure to various POPs through food consumption, but the correlations are not perfect.
Although POPs have long half-lives, body burden of POPs can change substantially during follow-up. Because the development of diabetes requires deterioration of glucose metabolism over the long term, prolonged and persistent exposure to POPs may be an important factor in a putative causal pathway linking POPs and diabetes. It is thought that there are interindividual and chemical-specific variations in excretion of POPs.
Under the low-dose effect, the selection of a reference group with very close to zero POP concentrations is critical to unbiased assessment of the risk of adverse health outcomes. As the CARDIA subjects in 1987-1988 had higher values of chlorinated POPs than present in the NHANES studies in 2003–2004, we cannot exclude the possibility that some risk gradient was still masked in our CARDIA subgroup, even when we used the lowest control group sextile to approximate more closely a true zero risk reference group in our nested case–control study.
The results from this study suggest that environmental exposure to some POPs may increase, in a nonlinear fashion, the risk of future type 2 diabetes in the general population. Various POPs, which mainly accu- mulate in adipose tissue, may play a critical role in the current epidemic of type 2 diabetes.
Additionally...
- low-dose effects (rapid rise in risk across low doses, with flattened or even attenuated risk at higher doses)
- p for quadratic term, or p for cubic term
- Lee DH, Jacobs DR Jr., Porta M. 2006a. Could low-level background exposure to persistent organic pollutants contribute to the social burden of type 2 diabetes? J Epidemiol Community Health 60(12):1006–1008.
- Lee DH, Lee IK, Song K, Steffes M, Toscano W, Baker BA, et al. 2006b. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999–2002. Diabetes Care 29(7):1638–1644.
