Arsenic exposure-related hyperglycemia is linked to insulin resistance with concomitant reduction of skeletal muscle mass
Arsenic exposure-related hyperglycemia is linked to insulin resistance with concomitant reduction of skeletal muscle mass
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DOI：
10.1016/j.envint.2020.105890
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发表时间：
2020-10-01
影响因子：
11.8
通讯作者：
Hossain, Khaled
中科院分区：
文献类型：
--
作者：
Mondal, Victor;Hosen, Zubaer;Hossain, Khaled
背景：大量证据表明砷暴露与糖尿病之间存在联系，但其潜在机制尚未阐明。目的：我们探讨砷暴露与骨骼肌质量减少之间的关系，作为胰岛素抵抗导致砷相关高血糖的潜在机制。方法：从孟加拉国砷流行区和非流行区招募了 581 名受试者，并测定了他们的空腹血糖 (FBG)、测定血清胰岛素和血清肌酐水平。通过水、头发和指甲中的砷浓度来评估受试者的砷暴露水平。 HOMA-IR和HOMA-beta分别用于计算胰岛素抵抗和β细胞功能障碍。血清肌酐水平和去脂体重（LBM）被用作肌肉质量指标。结果：无论男性还是女性，水、头发和指甲的砷浓度均与FBG、血清胰岛素和HOMA-IR呈显着正相关，与血清肌酐和LBM呈负相关，且呈剂量依赖性。在女性中，水、头发和指甲中的砷与 HOMA-β 呈显着负相关，但在男性中则不然。 FBG和HOMA-IR随着血清肌酐和LBM水平的降低而升高。随着水、头发和指甲中砷浓度的增加以及血清肌酐和LBM水平的降低，高血糖的比值比（OR）显着增加。女性的 HOMA-IR 显示对血清肌酐和 LBM 降低的敏感性更大，可能导致女性比男性出现更高血糖的风险。通径分析揭示了血清肌酐水平在砷暴露与HOMA-IR和高血糖关系中的中介作用。结论：砷暴露通过增加胰岛素抵抗而升高FBG水平和高血糖风险，且女性比男性更易受影响。此外，砷暴露相关的骨骼肌质量减少可能是胰岛素抵抗和高血糖发生的潜在机制。
Background: A large body of evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified.Objective: We explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia.Methods: A total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects' arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-beta were used to calculate insulin resistance and beta-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators.Results: Water, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-beta in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs) of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females' HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia.Conclusion: Arsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.