For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.

ObjectiveSeveral intervention studies have suggested that vegetarian or vegan diets have clinical benefits, particularly in terms of glycemic control, in patients with type 2 diabetes (T2D); however, no randomized controlled trial has been conducted in Asians who more commonly depend on plant-based foods, as compared to Western populations. Here, we aimed to compare the effect of a vegan diet and conventional diabetic diet on glycemic control among Korean individuals.Materials and MethodsParticipants diagnosed with T2D were randomly assigned to follow either a vegan diet (excluding animal-based food including fish; n = 46) or a conventional diet recommended by the Korean Diabetes Association 2011 (n = 47) for 12 weeks. HbA1c levels were measured at weeks 0, 4, and 12, and the primary study endpoint was the change in HbA1c levels over 12 weeks.ResultsThe mean HbA1c levels at weeks 0, 4, and 12 were 7.7%, 7.2%, and 7.1% in the vegan group, and 7.4%, 7.2%, and 7.2% in the conventional group, respectively. Although both groups showed significant reductions in HbA1C levels, the reductions were larger in the vegan group than in the conventional group (-0.5% vs. -0.2%; p-for-interaction = 0.017). When only considering participants with high compliance, the difference in HbA1c level reduction between the groups was found to be larger (-0.9% vs. -0.3%). The beneficial effect of vegan diets was noted even after adjusting for changes in total energy intake or waist circumference over the 12 weeks.ConclusionBoth diets led to reductions in HbA1c levels; however, glycemic control was better with the vegan diet than with the conventional diet. Thus, the dietary guidelines for patients with T2D should include a vegan diet for the better management and treatment. However, further studies are needed to evaluate the long-term effects of a vegan diet, and to identify potential explanations of the underlying mechanisms.Trial RegistrationCRiS KCT0001771

OBJECTIVE -We reported strong relations between serum concentrations of persistent organic pollutants (POPs), especially organochlorine (OC) pesticides or nondioxin-like polychlorinated biphenyls (PCBs), and prevalence of diabetes in a U.S population with background exposure to POPs. Here, we investigated POPs and insulin resistance, a frequent pathogenic precursor of type 2 diabetes.RESEARCH DESIGN AND METHODS -Serum POPs and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated cross-sectionally in 749 nondiabetic participants aged Ն20 years. Nineteen POPs in five subclasses were selected, detectable in Ն60% of participants.RESULTS -Among subclasses, OC pesticides were most strongly associated with HOMA-IR. Adjusted geometric means of HOMA were 3.27, 3.36, 3.48, and 3.85 (P for trend Ͻ0.01) across quartiles of OC pesticides. The relationship strengthened with increasing HOMA-IR percentile: adjusted odds ratios comparing the highest versus lowest POPs quartile were 1.8 for being Ն50th percentile of HOMA-IR, 4.4 for being Ն75th percentile, and 7.5 for being Ն90th percentile. Associations with elevated HOMA-IR appeared to be specific to oxychlordane and trans-nonachlor but also were found for two nondioxin-like PCBs. No HOMA-IR associations were seen in the other three POP subclasses. The association between OC pesticides and HOMA-IR tended to strengthen as waist circumference increased, with no apparent association in the lowest quartile of OC pesticide concentrations.CONCLUSIONS -These findings, coupled with those concerning diabetes prevalence, suggest that OC pesticides and nondioxin-like PCBs may be associated with type 2 diabetes risk by increasing insulin resistance, and POPs may interact with obesity to increase the risk of type 2 diabetes. Diabetes Care 30:622-628, 2007

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.

To investigate the prevalence of and the risk factors for human papillomavirus (HPV) infection in South Korea Key words: human papillomavirus; HPV DNA; HPV VLP antibodies; Korea; prevalence; risk factorsCertain high-risk types of human papillomavirus (HPV), most notably HPV types 16 and 18, are the necessary cause of invasive cervical cancer (ICC) and its related precursors. 1 The finding that nearly all ICC world-wide contain HPV DNA (99%) 2,3 has encouraged efforts to develop both prophylactic and therapeutic vaccines against HPV. 4 Newly developed prophylactic vaccines based on HPV virus-like particles (VLPs) have been demonstrated to be safe and highly immunogenic in humans. 5,6 Before HPV vaccines may be introduced at the population-level, age-specific data on the prevalence of genital HPV infection in population-based samples of women are needed. The availability of such data is still limited, 7-10 particularly in Asia. 11,12 The prevalence of serum IgG antibodies against virus-like particles (anti-VLPs) of the most common HPV types, mainly HPV 16, has been evaluated in several populations. 13,14 Anti-VLPs are considered good markers of cumulative HPV exposure but are relatively insensitive markers of current HPV infection. 13 In order to investigate whether differences in the age-specific prevalence of HPV infection in the female general population can explain the marked geographical variation in ICC incidence, the International Agency for Research on Cancer (IARC) coordinated a series of population-based prevalence surveys of HPV infection in areas with high and low incidence of ICC. 15 As part of this effort, a prevalence survey of HPV infection was conducted in Busan, South Korea, an area with intermediate ICC incidence rates (20.8/100,000 in 1996 -1997). 16 Pap smear for the early detection of cervical cancer was first recommended in Korea in 1985 by the medical insurance of governmental employees and school teachers, but it has not been widely used so far nor included in any population-based screening program. This paper reports results on the prevalence of and determinants for detection of cervical HPV DNA and serum anti-VLPs among women in South Korea. MATERIAL AND METHODS Study subjectsA population-based survey was carried out between November 1999 and March 2000 in Busan, the second largest city of South Korea with an estimated population of 3.8 million people. A 2-stage cluster sampling method was used to randomly select female residents aged 15 years or older from the S district. In the first stage, 4 of 16 dongs of the S district were randomly selected. In the second stage, 3 sub-units of each dong (tongs) were randomly selected. A list of all female residents aged 15 years or older (Nϭ2,684) from the 12 selected tongs was generated. Three hundred eighty-four women (14%) did not live at the given address, 260 (9.7%) refused to participate and 47 (1.5%) were not eligible due to exclusion criteria (non-Korean ethnicity, current pregnancy, history of previous hysterectomy or conization, and menta...

OBJECTIVE —Chlorinated persistent organic pollutants (POPs), endocrine disruptors accumulated in adipose tissue, were associated with diabetes and metabolic syndrome. Brominated flame retardants (BFRs), such as polybrominated diphenyl ethers (PBDEs) or polybrominated biphenyls (PBBs), are another class of POPs for which body burden is increasing. Cross-sectional associations of serum concentrations of BFRs with diabetes and metabolic syndrome were studied. RESEARCH DESIGN AND METHODS —In the National Health and Nutrition Examination Survey 2003–2004, 1,367 adults were examined with respect to diabetes status. Five PBDEs and one PBB were selected, detectable in ≥60% of participants. For the outcome metabolic syndrome, we restricted the analysis to 637 participants with a morning fasting sample. RESULTS —Compared with subjects with serum concentrations below the limit of detection, prevalent diabetes had differing dose-response associations with serum concentrations of PBB-153 and PBDE-153. Adjusted odds ratios across quartiles of serum concentrations for PBB-153 or PBDE-153 were 1.0, 0.7, 1.4, 1.6, and 1.9 ( P for trend <0.01) and 1.0, 1.6, 2.6, 2.7, and 1.8 ( P for quadratic term <0.01), respectively. PBB-153 was also positively associated with the prevalence of metabolic syndrome with adjusted odds ratios of 1.0, 1.5, 3.1, 3.1, and 3.1 ( P for trend<0.01). As in its association with diabetes, PBDE-153 showed an inverted U-shaped association with metabolic syndrome. CONCLUSIONS —Pending confirmation in prospective studies, lipophilic xenobiotics, including brominated POPs stored in adipose tissue, may be involved in the pathogenesis of diabetes and metabolic syndrome.

The rising rates of prostate cancer in South Korea cannot be attributed entirely to PSA screening due to the low PSA screening prevalence; this trend is most likely related to increased westernization among Koreans. Interdisciplinary epidemiological studies incorporating the collection of biological samples are needed to clarify the extent to which lifestyle and genetic factors contribute to the observed racial disparity.

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