Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?
Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?
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DOI：
10.1007/s00125-007-0896-5
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发表时间：
2008-03-01
期刊：
影响因子：
8.2
通讯作者：
Jacobs, D. R., Jr.
中科院分区：
文献类型：
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作者：
Lee, D. -H.;Steffes, M. W.;Jacobs, D. R., Jr.
几项血清γ-谷氨酰转移酶（GGT）流行病学研究的结果使我们假设GGT在正常范围内与2型糖尿病的关系可能反映了环境中发现的外源性物质（如持久性有机污染物（POP））的有害影响。流行病学观察表明，血清GGT活性在其正常范围内强烈预测未来的2型糖尿病;糖尿病的可预测性较低，GGT在正常范围的低端; GGT与已知的氧化应激或炎症标志物呈正相关。细胞GGT的实验结果表明，在正常范围内的血清GGT水平可能反映了与细胞内谷胱甘肽的再合成有关的氧化应激;然而，这种解释并不完全令人满意，因为在其再生细胞内谷胱甘肽的作用中，GGT活性应该是抗氧化的。或者，血清GGT活性可以反映外源性物质代谢过程中形成的谷胱甘肽结合物的量。因此，我们提出了一个两部分假设：血清GGT与2型糖尿病的相关性反映了持久性有机污染物的暴露，因为这些物质具有很长的半衰期，可能通过作为内分泌干扰物存在于脂肪组织中而影响糖尿病风险;持久性有机污染物或类似物质可能与肥胖相互作用，导致2型糖尿病。支持这一假设的是，在全国健康和营养检查调查中对持久性有机污染物背景暴露的横断面调查显示，与GGT观察到的关系相似，包括与流行性糖尿病的强有力的关联，而在极低的持久性有机污染物浓度下，肥胖与糖尿病之间没有关联。我们的假设可以在前瞻性研究和毒理学研究中得到验证。
The results of several epidemiological studies of serum gamma-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. Alternatively, serum GGT activity may reflect amounts of glutathione conjugates formed during the metabolism of xenobiotics. Accordingly, we postulate a two-part hypothesis: that the association of serum GGT with type 2 diabetes reflects exposure to POPs, as these substances, which have a very long half-life, may influence diabetes risk by residing in adipose tissue as endocrine disruptors; and that POPs or similar substances may interact with obesity to cause type 2 diabetes. Supporting this hypothesis, cross-sectional investigation of background exposure to POPs in the National Health and Nutrition Examination Survey showed relationships similar to those observed for GGT, including a powerful association with prevalent diabetes and no association between obesity and diabetes for very low POP concentrations. Our hypothesis can be tested in both prospective studies and toxicological studies.