Phthalates exposure, biological aging, and increased risks of insulin resistance, prediabetes, and diabetes in adults with metabolic dysfunction-associated steatotic liver disease - 20/12/24

Doi : 10.1016/j.diabet.2024.101602

Yueru Yang ^a,^b, Shuhui Wan ^a,^b, Linling Yu ^a,^b, Wei Liu ^a,^b, Jiahao Song ^a,^b, Da Shi ^c, Yongfang Zhang ^a,^b, Weihong Chen ^a,^b, Weihong Qiu ^d,^⁎ , Bin Wang ^a,^b,^⁎
^a Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China
^b 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
^c Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
^d Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, PR China

^⁎Corresponding author at: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.Department of Occupational and Environmental HealthSchool of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030PR China^⁎⁎Corresponding author at: Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, PR China.Department of Epidemiology and Health Statistics, School of Public HealthFujian Medical UniversityFuzhou350122PR China

Highlights

•	Exposure of MASLD adults to phthalates was positively linked to IR, prediabetes, and diabetes.
•	Positive effects of single and mixture phthalates exposure on outcomes were found.
•	Biological aging was positively related to IR, prediabetes, and diabetes in MASLD adults.
•	Biological aging aggravated IR, prediabetes, and diabetes risks linked to phthalates exposure.

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Abstract

Aim

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).

Methods

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.

Results

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_interaction = 0.031), prediabetes 1.975 [1.189;3.278] (P_interaction = 0.009), and diabetes 6.065 [3.210;11.460] (P_interaction = 0.013).

Conclusion

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.

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Keywords : Biological aging, Diabetes, Insulin resistance, Metabolic dysfunction-associated steatotic liver disease, Phthalates, Prediabetes

Abbreviations : NHANES, MASLD, FPG, FINs, HOMA-IR, IR, HSI, US FLI, MEOHP, MEP, MEHHP, MECPP, MnBP, MEHP, MiBP, MBzP, MCPP, MCNP, MCOP, BA, PA, BMI, eGFR, WQS, OR, CI