Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Environ Res. 2020 Feb;181:108916. doi: 10.1016/j.envres.2019.108916. Epub 2019 Nov 14.
Cardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population.
To describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD.
Pesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type.
Participants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: -0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of -0.64 (-1.17, -0.11) for 2,4-D and -0.39 (-0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (-0.11, 3.01) higher and log FCP levels that were -0.28 (-0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up.
Exposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes.
心血管疾病 (CVD) 是糖尿病患者死亡的主要原因，但对于环境化学物质（如农药）暴露在这一人群 CVD 风险早期发展中的作用知之甚少。
描述美国糖尿病青少年中农药生物标志物浓度随时间的变化，并估计这些浓度与 CVD 既定风险因素之间的纵向关联。
对参加多中心 SEARCH 队列研究的 87 名糖尿病青少年的尿液和血清样本进行了农药生物标志物定量检测。样本是在诊断时（基线访问，2006 年至 2010 年之间）和平均 5.4 年后（随访访问，2012 年至 2015 年之间）获得的。我们计算了农药生物标志物浓度的几何平均值（95%CI）。在这两个时间点测量了 8 个 CVD 风险因素：体重指数 (BMI) z 分数、HbA1c、胰岛素敏感性、空腹 C 肽 (FCP)、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、总胆固醇和甘油三酯。使用线性回归模型估计每个基线农药生物标志物与随访时每个 CVD 风险因素之间的关联，调整了基线健康结果、基线与随访之间的时间间隔、性别、年龄、种族/民族和糖尿病类型。
参与者在基线访问时平均年龄为 14.2 岁，大多数被诊断为 1 型糖尿病（57.5%）。4-硝基酚、3-苯氧基苯甲酸、2,4-二氯苯氧基乙酸（2,4-D）、3,5,6-三氯-2-吡啶醇、2,2-双（4-氯苯基）-1,1-二氯乙烯和六氯苯在两个时间点都被大多数参与者检测到。基线时 2,4-D 和 4-硝基酚四分位最高的参与者，与基线时这些农药生物标志物四分位最低的参与者相比，HbA1c 水平分别高 1.05 个百分点（95%CI：-0.40，2.51）和 1.27 个百分点（0.22，2.75）。与基线时四分位最低的参与者相比，这些参与者的 log FCP 水平也较低（表示β细胞功能降低）：2,4-D 的 log FCP 为 -0.64（95%CI：-1.17，-0.11），4-硝基酚为 -0.39（95%CI：-0.96，0.18）。换句话说，2,4-D 四分位最高的参与者的 FCP 水平比四分位最低的参与者低 47.3%，4-硝基酚四分位最高的参与者的 FCP 水平比四分位最低的参与者低 32.3%。基线时 trans-nonachlor 浓度处于四分位最高的参与者，HbA1c 水平高 1.45 个百分点（95%CI：0.11，3.01），log FCP 水平低 0.28（95%CI：-0.84，0.28），低于基线时四分位最低的参与者，也就是说，trans-nonachlor 四分位最高的参与者的 FCP 水平比四分位最低的参与者低 24.4%。虽然并非所有这些结果都具有统计学意义，可能是由于样本量较小，但从临床角度来看，似乎存在定量差异。在基线时任何农药生物标志物与随访时 BMI z 分数或胰岛素敏感性之间均未观察到关联。
暴露于某些农药可能与糖尿病青少年的β细胞功能受损和血糖控制恶化有关。
