Yang Yueru, Wan Shuhui, Yu Linling, Liu Wei, Song Jiahao, Shi Da, Zhang Yongfang, Chen Weihong, Qiu Weihong, Wang Bin
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
Diabetes Metab. 2025 Jan;51(1):101602. doi: 10.1016/j.diabet.2024.101602. Epub 2024 Dec 10.
To estimate the individual and combined influences of phthalates and biological aging on insulin resistance (IR), prediabetes, and diabetes in population with metabolic dysfunction-associated steatotic liver disease (MASLD).
Data on 3,045 US adults with MASLD were collected to outline the individual and mixed effects of urinary phthalate metabolites on prevalent IR, prediabetes, and diabetes by survey-weighted logistic regression and weighted quantile sum (WQS) regression, as well as the interaction effects between phthalates and biological aging.
We discovered positive relationships - odds ratio (OR) and 95 % confidence interval [CI] - of mono-2-ethyl-5-carboxypentyl phthalate 1.147 [1.041;1.264], mono-(2-ethyl-5-hydroxyhexyl) phthalate 1.175 [1.073;1.288], and mono-(2-ethyl-5-oxohexyl) phthalate 1.140 [1.040;1.250] with IR, and of mono-isobutyl phthalate with prediabetes 1.216 [1.064;1.390] (all FDR-adjusted P < 0.05). WQS analyses indicated significantly mixed effects of phthalate metabolites on the elevated risks of IR 1.166 [1.034;1.315], prediabetes 1.194 [1.006;1.416], and diabetes 1.214 [1.026;1.437]. Biological age (BA) and phenotypic age (PA) were positively associated with IR, prediabetes, and diabetes and further significantly interacted with phthalates on the outcomes; typically, compared to participants with low levels of phthalates mixture and PA, those with high levels of phthalates mixture and PA had the highest risks of IR 2.468 [1.474;4.133] (P = 0.031), prediabetes 1.975 [1.189;3.278] (P = 0.009), and diabetes 6.065 [3.210;11.460] (P = 0.013).
Phthalates exposure of MASLD adults was related to increased risks of IR, prediabetes, and diabetes, which were interactively aggravated by biological aging. Controlling phthalates exposure and biological aging probably hold significant relevance for the prevention of diabetes in the MASLD population.
评估邻苯二甲酸盐和生物衰老对代谢功能障碍相关脂肪性肝病（MASLD）人群胰岛素抵抗（IR）、糖尿病前期和糖尿病的个体及综合影响。
收集了3045名美国成年MASLD患者的数据，通过调查加权逻辑回归和加权分位数和（WQS）回归来概述尿邻苯二甲酸酯代谢物对普遍存在的IR、糖尿病前期和糖尿病的个体及混合效应，以及邻苯二甲酸盐与生物衰老之间的交互作用。
我们发现邻苯二甲酸单-2-乙基-5-羧基戊酯的比值比（OR）和95%置信区间[CI]为1.147[1.041；1.264]、邻苯二甲酸单-（2-乙基-5-羟基己基）酯为1.175[1.073；1.288]、邻苯二甲酸单-（2-乙基-5-氧代己基）酯为1.140[1.040；1.250]与IR呈正相关，邻苯二甲酸单异丁酯与糖尿病前期的OR为1.216[1.064；1.390]（所有FDR校正P<0.05）。WQS分析表明邻苯二甲酸酯代谢物对IR风险升高1.166[1.034；1.315]、糖尿病前期1.194[1.006；1.416]和糖尿病1.214[1.026；1.437]有显著的混合效应。生物年龄（BA）和表型年龄（PA）与IR、糖尿病前期和糖尿病呈正相关，并且在这些结局上与邻苯二甲酸盐进一步存在显著交互作用；通常，与邻苯二甲酸盐混合物和PA水平低的参与者相比，邻苯二甲酸盐混合物和PA水平高的参与者患IR的风险最高，为2.468[1.474；4.133]（P=0.031），糖尿病前期为1.975[1.189；3.278]（P=0.009），糖尿病为6.065[3.210；11.460]（P=0.013）。
MASLD成年患者接触邻苯二甲酸盐与IR、糖尿病前期和糖尿病风险增加有关，生物衰老会使其交互加剧。控制邻苯二甲酸盐暴露和生物衰老可能对预防MASLD人群中的糖尿病具有重要意义。
