Environmental exposure to phthalates has been implicated in metabolic disturbances in prior research, but prospective evidence remains limited. This population-based cohort study used Taiwan Biobank data to investigate whether baseline urinary phthalate metabolite concentrations are associated with subsequent changes in metabolic risk markers, incident metabolic syndrome (MetS), and incident type 2 diabetes mellitus (T2DM).
Data were drawn from the Taiwan Biobank. Eligible participants included those with baseline urinary measurements of phthalate metabolites and without pre-existing MetS. The MetS analysis included 790 participants; a subset of 556 participants without pre-existing T2DM was followed for incident diabetes.
Urinary concentrations of 10 phthalate metabolites were quantified using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Phthalate metabolites reported in the abstract include metabolites of dibutyl phthalate (DBP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and DEHP metabolites among others. Concentrations were analyzed on the natural-log scale in regression models.
Primary outcomes included changes between baseline and follow-up in waist circumference, blood pressure, blood glucose measures including HbA1c, and lipid profiles (triglycerides, total cholesterol, HDL-c). Incident MetS during follow-up and incident T2DM identified through linkage to participants' medical records were secondary outcomes of interest. Mean follow-up time reported was 4.25 years.
The investigators used multivariable linear regression models to evaluate continuous changes in metabolic markers, logistic regression models for MetS incidence, and Cox proportional hazards regression for time-to-event analysis of incident T2DM. Models were adjusted for covariates (not detailed in the abstract). False-discovery-rate (FDR) correction was applied to account for multiple comparisons.
Among 790 participants followed for a mean of 4.25 years, 102 (12.9%) developed MetS. The study abstract states that no association was observed between baseline phthalate metabolite concentrations and MetS prevalence after analysis.
Analyses of continuous metabolic measures found that each ln-unit increase in baseline MiBP was associated with a greater increase in HbA1c of 0.04%. Associations between MiBP and increases in triglycerides and total cholesterol were observed in initial models, and some associations between DEHP metabolites and increased HbA1c and decreased HDL-c were reported, but these did not remain statistically significant after FDR correction for multiple testing.
Among 556 participants without pre-existing T2DM, 22 (3.96%) developed incident T2DM during follow-up. Each ln-unit increase in baseline MnBP was associated with a 1.82-fold higher adjusted risk of incident T2DM; however, this association lost statistical significance after FDR correction. No other phthalate–T2DM associations that remained significant after multiple-comparison correction were reported in the abstract.
The authors report that neither sex nor age significantly modified the observed associations between phthalate metabolites and metabolic outcomes. Specific details of sensitivity analyses, covariates included in models, or subgroup effect estimates were not provided in the abstract.
In this prospective cohort, markers of DBP exposure (MiBP and MnBP) were associated with small deteriorations in HbA1c and with initial signals of increased lipid measures; an elevated adjusted risk of incident T2DM with higher MnBP was observed before correction for multiple testing. However, several associations—including those for DEHP metabolites and for DBP measures with some lipid outcomes—did not remain statistically significant after false-discovery-rate correction. The authors conclude that DBP exposure was linked to deterioration in glycemic control and lipid profiles, while the potential association between DBP exposure and increased T2DM risk requires further confirmation in additional studies.
Limitations implied by the abstract include reliance on a single baseline urinary phthalate measurement, potential residual confounding, and attenuation of findings after multiple-comparison correction; full methodological detail and covariate lists are not reported in the abstract.
The authors declare competing interests as follows: Chin-Li Lu reports financial support from the National Science and Technology Council in Taiwan. Other authors declared no known competing financial interests or personal relationships that could have influenced the work.
This Taiwan Biobank-based prospective analysis adds evidence that higher baseline urinary DBP metabolites correlate with small adverse changes in HbA1c and lipid measures over approximately four years. Signals linking DBP metabolites to incident T2DM were observed but did not retain significance after FDR correction, underscoring the need for replication and further longitudinal analyses with detailed adjustment and repeated exposure assessment.