Search

Background: Global DNA methylation levels have been reported to be inversely associated with blood levels of persistent organic pollutants (POPs), xenobiotics that accumulate in adipose tissue. Whether these associations extend to a population with much lower concentrations of POPs is not known., Objectives: This study was performed to examine whether low-dose exposure to POPs was associated with global DNA hypomethylation in Koreans., Methods: The amount of global DNA hypomethylation was estimated by the percent 5-methyl-cytosine (%5-mC) in Alu and LINE-1 assays in 86 apparently healthy Koreans. Among various POPs, organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenylethers (PBDEs) were measured., Results: Most OC pesticides were inversely and significantly associated with %5-mC in the Alu assay, with correlation coefficients in the range 0.2 to 0.3 after adjusting for age, sex, body mass index, smoking, and alcohol. The strongest OC pesticide associations with %5-mC in the Alu assay were observed with oxychlordane, trans-nonachlor, and p,p -dichlorodiphenyldichloroethylene. The correlation coefficient of age with %5-mC in the Alu assay was 0.24, similar to correlations of OC pesticides with %5-mC in the Alu assay. Most PCBs and PBDEs showed nonsignificant inverse trends with %5-mC in the Alu assay, but for some PCBs the U-shaped association was significant. On the other hand, POPs were not associated with %5-mC in the LINE-1 assay., Conclusions: We found that low-dose exposure to POPs, in particular OC pesticides, was associated with global DNA hypomethylation in apparently healthy Koreans.

Objective: Recent epidemiological studies have shown that background exposure to persistent organic pollutants (POPs)--xenobiotics accumulated in adipose tissue--is strongly associated with type 2 diabetes. Hyperglycemia is the cause of long-term complications of diabetes as well as diabetes itself, and POPs are well-known neurotoxicants. This study was performed to explore whether POPs are associated with peripheral neuropathy, a common long-term complication of diabetes, in people with glucose abnormalities., Research Design and Methods: We studied cross-sectional associations of peripheral neuropathy with 25 POPs, each of which were detectable in at least 60% of study subjects, in 246 subjects aged >or=40 years with diabetes or impaired fasting glucose (IFG) using National Health and Nutrition Examination Survey 1999-2002 datasets., Results: Among five subclasses of POPs, organochlorine pesticides showed a strong dose-response relation with prevalence of peripheral neuropathy; adjusted ORs were 1.0, 3.6, and 7.3 (P for trend <0.01), respectively, across three categories of serum concentrations of organochlorine pesticides. Furthermore, when we restricted the analyses to 187 participants with A1C <7%, the adjusted ORs were still 1.0, 3.9, and 6.7 (P for trend <0.01). Organochlorine pesticides were also strongly associated with the prevalence of A1C >or=7%; adjusted ORs were 1.0, 2.5, and 5.0 (P for trend <0.01). Specific POPs belonging to organochlorine pesticides showed similar positive associations., Conclusions: This study suggests that background exposure to organochlorine pesticides may be associated with higher risk of peripheral neuropathic complications among those with glucose abnormalities, even beyond the influence of diabetes itself.

Aims/hypothesis: Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes., Methods: A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication., Results: There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration., Conclusion/interpretation: This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.