Association of type 2 diabetes mellitus with plasma organochlorine compound concentrations

Abstract

The increased prevalence of type 2 diabetes mellitus (T2DM) is associated with obesity, age, and sedentary lifestyle, but exposure to some organochlorine (OC) compounds has also been recently implicated. The hypothesis tested is that higher concentrations of bioaccumulative OC compounds are associated with T2DM. Plasma samples were obtained from a cross-section of adult male and female Caucasians and African Americans, either with or without T2DM from two US Air Force medical facilities. A method of extracting OC compounds from human plasma using solid phase extraction was developed, and three OC compounds [p,p'-DDE (DDE), trans-nonachlor, and oxychlordane] were quantified by gas chromatography/mass spectrometry. Multivariable logistic regression modeling indicated that increasing body mass index (BMI) was associated with T2DM in Caucasians but not in African Americans, and African Americans were more likely to have T2DM than Caucasians with decreasing odds ratios as BMI increased. An association between T2DM and increasing plasma DDE (adjusted for age, base, race, and BMI) was observed. Increasing DDE concentrations were associated with T2DM in older individuals and those with lower BMIs. Thus, in this study sample there was a higher risk of T2DM with increasing DDE concentrations in older people of normal weight and relatively lower risk associated with increasing DDE concentrations in those who are overweight or obese.

Organochlorine Insecticides Induce NADPH Oxidase-Dependent Reactive Oxygen Species in Human Monocytic Cells via Phospholipase A2/Arachidonic Acid

“…4 In addition, plasma levels of p , p ′-DDE were higher in type 2 diabetics than in normal patients in a cross-sectional study of two U.S. Air Force medical facilities. 48 The purpose of this study was to explore one such potential mechanism by characterizing the ability of bioaccumulative organochlorine insecticides to stimulate ROS production in human monocytes and to examine the signaling mechanisms involved. In cells, superoxide flux is defined by the difference between its rates of production and degradation.…”

Exposure to DDT metabolitep,p′-DDE increases autoimmune type 1 diabetes incidence in NOD mouse model

“…Numerous epidemiological studies indicate a link between DDE and induction of T2D (Eden et al, 2014;Tang et al, 2014;Taylor et al, 2013). Retrospective epidemiological analysis showed that increased levels of DDE in the human sera were positively correlated with increased insulin resistance (Lee et al, 2007) and prevalence of T2D (Lee et al, 2006).…”

“…While a large number of studies about the association between DDE and the prevalence of T2D exist (Eden et al, 2014;Tang et al, 2014;Taylor et al, 2013), there is only one epidemiological study that explores DDE exposure and T1D development (Rignell-Hydbom et al 2010). Moreover, there has been no study designed to directly answer that question in an experimental model of T1D.…”

The association of serumtrans-nonachlor levels with atherosclerosis

“…Serum OC compounds were extracted using DPX Labs reverse-phase extraction columns as previously described in Eden et al (2014). Briefly, 1 ml serum (stored frozen at −80°C) was thawed and 100 µl internal standard solution containing [ 13 C]- p , p ’-DDT and [ 13 C]- trans -nonachlor in hexane (final concentrations, 0.01 µg/ml) was added to each sample.…”

“…Although the use of bioaccumulative OC compounds like DDT and chlordane has been banned in the United States for decades, these legacy OC compounds and/or their metabolites and degradation products are still detected in serum samples in human populations within the United States and abroad, as well as in the US food supply (CDC, 2009; Eden et al, 2014). …”