Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

Abstract

The results of several epidemiological studies of serum γ-glutamyltransferase (GGT) led us to hypothesise that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment, such as persistent organic pollutants (POPs). Epidemiological observations showed that serum GGT activity within its normal range strongly predicted future type 2 diabetes; the predictability of diabetes from obesity was low with GGT at the low end of the normal range; and GGT showed a positive association with known markers of oxidative stress or inflammation. Experimental findings on cellular GGT suggest that serum GGT levels within the normal range may reflect oxidative stress related to the re-synthesis of intracellular glutathione; however, this interpretation is not completely satisfying because, in its role of regenerating intracellular glutathione, GGT activity should be antioxidative.

Impact of environmental endocrine disrupting chemicals on the development of obesity

“…13 Other studies report a link between some persistent organic pollutants and increased body weight and diabetes; 14 furthermore, non-dioxin PCBs were shown to be inversely associated with BMI but organochlorine pesticides to be positively associated with BMI. 15,16 These data support earlier findings which also reported a positive correlation between plasma organochlorine concentrations and BMI and fat mass. 17 Also, studies focusing on in utero exposure linked hexachlorobenzene exposure during pregnancy to a higher risk of overweight in children at 6 years of age.…”

High prevalence of prediabetes and diabetes in a population exposed to high levels of an organochlorine cocktail

“…Results of these studies indicate that the association between serum γ-glutamyltransferase and type 2 diabetes was stronger in obesity and that obesity could not predict the risk of type 2 diabetes among participants with γ-glutamyltransferase at the low end of the normal range. This observation led to the hypothesis that the association of γ-glutamyltransferase with type 2 diabetes reflects exposure to POPs, since these reside in adipose tissue as endocrine disruptors and thus may interact with obesity to cause type 2 diabetes [41].…”

Effects of Oral Glutathione Supplementation on Systemic Oxidative Stress Biomarkers in Human Volunteers

“…1 GSH is an important antioxidant and plays a major role in the detoxification of endogenous metabolic products, including lipid peroxides, and xenobiotic compounds including pollutants, heavy metals, and drugs. 2,3 Intracellular GSH exists in both the oxidized disulfide form (GSSG) or in reduced (GSH) state; the ratio between GSH and GSSG is held in dynamic balance depending on many factors including the tissue of interest, intracellular demand for conjugation reactions, intracellular demand for reducing power, extracellular demand for reducing potential, and the complex interplay between several regulatory enzymes including glutathione peroxidase (GPx), glutathione-Stransferase (GST) and c-glutamyltransferase (GGT). 1 In the absence of adequate GSH concentrations, numerous oxidative and nitrosative reactive intermediates persist, including superoxide, hydroxide, peroxide, and peroxynitrite radicals, which all can lead to modification of cellular macromolecules including lipid membranes (measured in vivo by F2-isoprostanes) and DNA adduct formation (measured in vivo by 8-hydroxy-2'-deoxyguanosine ).…”