Exposure to Phthalates Linked to Diabetes in Midlife Among White Women

Sung Kyun Park, ScD, MPH

New research suggests greater cumulative exposure to phthalates could increase a woman’s risk of developing diabetes later in life.

An analysis of data from more than 1300 participants of the landmark Study of Women’s Health Across the Nation (SWAN), results of the study demonstrate exposure to phthalates was associated with a 30-63% greater risk of developing diabetes among White women.¹

"Our research found phthalates may contribute to a higher incidence of diabetes in women, especially White women, over a six-year period,” said Sung Kyun Park, ScD, MPH, of the University of Michigan School of Public Health.² “People are exposed to phthalates daily increasing their risk of several metabolic diseases. It’s important that we address EDCs now as they are harmful to human health.”

Few could have expected industrialization and modernization witnessed in the last 100 years would have such a profound impact on endocrinology in the decades to come. As many have begun to point the finger at changes in nutrition and food sources for their role in the obesity epidemic, research into the effects of phthalates and other endocrine-disrupting chemicals (EDCs) in modern products has exploded, with the understanding surrounding the effects of EDCs growing with each passing year.

Citing previous research linking phthalate exposure to diabetes and with funding from the National Institutes of Health, Park and a team of investigators sought to examine this association leveraging data from the SWAN Multipollutant Study. Initiated by Park and a team of colleagues at the University of Michigan in 2016 to assess the effects of environmental chemical exposures³, the SWAN Multipollutant Study provided Investigators with information related to 1308 women who were without diabetes in 1999-2000 and had a follow-up time of 6 years.¹ As part of the SWAN study, spot urine samples were collected in 1999-2000 and gain in 2002-2003. From these, investigators planned to assess levels of 11 phthalate metabolites.

Incident diabetes was ascertained between 1999-2000 and 2005-2006, with incident diabetes defined using 3 potential criteria: reporting use of antidiabetic medications at any visit, having fasting glucose at or exceeding 126 mg/dL for 2 consecutive visits, or having a self-reported doctor’s diagnosis of diabetes at 2 visits and had fasting glucose at or exceeding 126 mg/dL at 1 visit. For the purpose of analysis, investigators used Cox proportional hazards models with time-varying exposure to estimate hazard ratio (HR) of diabetes for each of the 11 phthalate metabolites, with adjustment for demographics, lifestyle, and health-related factors. Investigators pointed out effect modification by race/ethnicity was examined with interaction terms.

Of the 1308 women identified for inclusion, 61 (4.7%) developed diabetes over the 6-year follow-up period. Results of the investigators’ analyses indicated there were several high-molecular-weight phthalate metabolites associated with higher incidence of diabetes, but none reach statistical significance and effect modification by race/ethnicity was observed. Investigators called attention to results suggesting each doubling of the concentrations of mono-isobutyl phthalate (MiBP), monobenzyl phthalate, mono-carboxyoctyl phthalate, mono-carboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate was associated with a 30% to 63% higher incidence of diabetes (HR, 1.30 [95% CI, 1.03-1.65] for MCNP; HR, 1.63 [95% CI, 1.18-2.25] for MiBP) among White women. These associations with increased incidence were not seen among Black or Asian women.¹

“Our research is a step in the right direction towards better understanding phthalates’ effect on metabolic diseases, but further investigation is needed,” Park said.²

References

1. Park SK, Mukherjee B, Herman WH, et al. Phthalates and Incident Diabetes in Midlife Women: The Study of Women’s Health Across the Nation (SWAN). Journal of Clinical Endocrinology and Metabolism. February 2023. doi:10.1210/clinem/dgad033
2. Williams C. Phthalate exposure may increase diabetes risk in women. EurekAlert. https://www.eurekalert.org/news-releases/978706. Published February 8, 2023. Accessed February 8, 2023.
3. Mark Otto JT. SWAN Multi-Pollutant Study. Center for midlife science: Swan multi-pollutant study. https://midlifescience.umich.edu/Projects_SWAN_Pollutant.php. Accessed February 8, 2023.