Relationship between serum concentrations of persistent organic pollutants and markers of insulin resistance in a cohort of women with a history of gestational diabetes mellitus
Introduction
There has been a dramatic surge in the prevalence of diabetes over the last few decades, with the prediction of 366 million individuals with the disease worldwide by 2030 (Wild et al., 2004). Approximately 90% of the burden of diabetes is due to type 2 diabetes and 10% due to type 1 diabetes or gestational diabetes mellitus (GDM). GDM, i.e., glucose intolerance with onset or diagnosis during pregnancy, has an estimated prevalence of 8.8% in Spain (Ricart et al., 2005) and is considered a risk factor for the development of type 2 diabetes (Buchanan and Xiang, 2005).
Onset of type 2 diabetes is commonly preceded by early metabolic changes (prediabetes), including a progressive development of insulin resistance, which is first compensated by the over-production of insulin by beta cells until the insulin production becomes inadequate (Hsueh et al., 2010). The effects of insulin include a reduction in blood glucose and free fatty acids, the latter being derived from a suppression of lipolysis (Campbell et al., 1992). Hence, assuming equal insulin levels, higher blood glucose levels are related to lower insulin sensitivity.
There is increasing evidence that environmental factors play an important role in the increased prevalence of diabetes, because human exposure to certain pollutants can trigger or at least exacerbate glucose homeostasis disorders that commonly result in diabetes mellitus (Hectors et al., 2011). However, the mechanisms underlying this action have not yet been fully elucidated. Chronic exposure to low doses of persistent organic pollutants (POPs), a group of lipophilic chemicals highly resistant to degradation, has been acknowledged as a risk factor for diabetes (Lee et al., 2011b). POPs suspected of inducing diabetes include organochlorine pesticides, which have long been widely used as highly effective pest control agents, and polychlorinated biphenyls (PCBs), used in numerous industrial and commercial applications.
Dichlorodiphenyltrichloroethane (DDT) is an organochlorine pesticide that has been used extensively worldwide in agriculture and for vector control since 1939 (Turusov et al., 2002). Once in the environment or living organisms, DDT is mainly metabolized to p,p′- dichlorodiphenyldichloroethylene (p,p′-DDE), which is even more persistent than its parent compound (UNEP, 1999). Hexachlorobenzene (HCB) was first introduced in 1945 as a fungicide to treat onions, sorghum, and similar crops. Other sources of HCB include the emission of chemical industry by-products, impurities in organochlorine pesticide mixtures, combustion reactions, wood preservation agents, and metallurgical processes (Barber et al., 2005). Technical hexachlorocyclohexane (HCH, mixture of isomers) and lindane (mainly γ-HCH) are among the most extensively applied organochlorine pesticides, and the isomer β-HCH has proven the most persistent in the environment and living organisms. They were used from the late 1940s, mainly as insecticides in wood and wooden structures, seed grains, and livestock (Agency for Toxic Substances and Disease Registry, 2005), but also for rodent control in crops and seed stores and for the treatment of scabies and lice in personal use products (U.S.Department of Health and Human Services, 2011).
PCBs, manufactured since 1929, have been used in numerous industrial and commercial applications, including transformer and capacitor oils, hydraulic and heat exchange fluids, and lubricating and cutting oils (La Rocca and Mantovani, 2006).
Restrictions in most countries on the use and production of POPs have caused a progressive reduction in exposure of the general population. However, the fact that virtually all populations still show detectable internal levels of POPs is a matter of concern (Porta et al., 2003). In addition, it has been proposed that POP exposure can have a paradoxical effect, with more severe alterations in glucose homeostasis produced by low versus high exposure levels (Lee et al., 2006).
We hypothesized that the diabetogenic effect of POPs might be more readily detected in women with GDM, given their increased risk of developing further insulin resistance. Hence, our aim in this study was to assess the relationship between serum concentrations of a group of POPs and insulin resistance markers in women diagnosed with GDM.
Section snippets
Study population
The study population was prospectively recruited between 2005 and 2007 from among women diagnosed with GDM at the Endocrinology Service of San Cecilio University Hospital of Granada (Spain). GDM was diagnosed according to the criteria of the National Diabetes Data Group (National Diabetes Data Group, 1979).
Out of 109 women invited to participate in the study, consent was obtained from 107 (98%), who constituted the final study population. All women signed informed consent to participate in the
Results
Out of the 107 women with a history of GDM recruited in the study, 10 (9.3%) were diagnosed with type 2 diabetes after the OGTT according to WHO criteria (World Health Organization and International Diabetes Federation, 2006). The main characteristics of the study population and POP concentrations found in serum are summarized in Table 1. Median age was 36 yrs, median BMI was within the overweight range (27 kg/m2), and 21 (19.6%) women were current smokers. A diagnosis of GDM during a previous
Discussion
This study reports positive associations between several POP concentrations and markers of insulin resistance in a cohort of women with a history of GDM, which is in agreement with recent findings of associations between exposure to POPs and a higher risk of diabetes or increased insulin resistance (Airaksinen et al., 2011, Arrebola et al., 2013, Gasull et al., 2012, Lee et al., 2011a, Wu et al., 2012).
We observed consistent associations of three PCB congeners and HCB with HOMA2-IR and ISI-gly
Conflict of interest
The authors declare no relevant conflicts of interest to disclose.
Acknowledgements
The authors gratefully acknowledge editorial assistance provided by Richard Davies. This study was supported in part by research grants from the CIBER de Epidemiología, Junta de Andalucía (73/99, 274/04, EF-0708-2013, and PI-0513/2012), and Instituto de Salud Carlos III (00/1047 and PI11/0610). Dr JP Arrebola is currently under a postdoctoral contract from the Junta de Andalucía (RH-0092-2013). F. Artacho-Cordón has a fellowship from the Spanish Ministry of Education (FPU12/02524). The results
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2020, Ecotoxicology and Environmental SafetyCitation Excerpt :HbA1c, as another marker of glycemic control, can reflect blood glucose levels over a long period of time. However, no significant association was found between OCPs and HbA1c in the present study, which was consistent with some but not all previous studies (Arrebola et al., 2015; Dirinck et al., 2014; Turyk et al., 2015; Zong et al., 2018). Table 4 shows the β coefficients and 95% CIs from the multiple linear regressions for the associations of OCPs with lipid fractions in control participants without diabetes.