Middle-aged White women who had higher levels of some breakdown products of phthalates — a class of endocrine disrupting chemicals (EDCs) or “forever chemicals” that act as plasticizers — had a significantly greater risk of developing type 2 diabetes over a 6-year period than other similar women.
However, this association was not seen among Black or Asian middle-aged women.
These findings from the Study of Women’s Health Across the Nation Multipollutant Study (SWAN-MPS), by Mia Q. Peng, PhD, MPH, and colleagues, have been published online in the Journal of Clinical Endocrinology & Metabolism.
“Overall, our study has added some evidence to support the potential diabetogenic effects of phthalates, but it also highlights that much is still unknown about the metabolic effects of these chemicals,” the group summarizes.
“The apparent racial/ethnic differences in the associations between phthalates and incident diabetes should be investigated in future studies,” they caution.
Recruiting younger participants and observing them longer, they suggest, “will also help us understand the effects of phthalates on different stages of the diabetogenic process, including whether body fat gain is an important mediator.”
Phthalates Are All Around Us
Low-molecular-weight phthalates are frequently added to personal care products, such as fragrance, nail polish, and some feminine hygiene products, as solvents, plasticizers, and fixatives, the researchers explain.
And high-molecular-weight phthalates are frequently added to polyvinyl chloride plastic products, such as plastic food packaging, clothing, and vinyl flooring, as plasticizers.
Phthalates have been hypothesized to contribute to the development of diabetes, but longitudinal evidence in humans was limited.
“Given widespread exposure to phthalates and the enormous costs of diabetes to individuals and societies, ongoing investments in the research on phthalates’ metabolic effects are warranted,” the researchers conclude.
Racial Differences in Phthalates and Incident Diabetes
“A new finding is that we observed some phthalates are associated with a higher risk of diabetes development, especially in White women [that] were not seen in Black or Asian women,” senior author Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, told Medscape Medical News in an email.
“We were surprised to see the racial/ethnic differences,” Peng, formerly from the University of Michigan, but now at the Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus, added.
A possible explanation is that “compared to White women, Black women develop diabetes at a younger age and are exposed to higher levels of several phthalates,” and this study excluded women who already had diabetes by midlife, she noted.
“Although our study was conducted in a cohort of women,” Park stressed, “we hope that our findings are not interpreted that only women should be concerned of phthalates. Our findings add to the current literature that phthalates may be a potential risk factor for type 2 diabetes.”
“Certain phthalates are prohibited in children’s toys and childcare articles,” Peng noted, as explained by the US Consumer Product Safety Commission. In addition, a bill has been introduced in Congress to ban phthalates in food contact substances.
“If phthalates are removed from plastics and other consumer products,” she cautioned, “we do have to be careful in the process to avoid replacing them with some other potentially harmful chemicals.”
A well-known example of this type of “regrettable substitution,” Park added, “is ‘BPA-free’ plastics that replaced bisphenol A with other bisphenols such as bisphenol-F (BPF) or bisphenol-S (BPS). The product has a label of ‘BPA-free’, but those replaced chemicals turned out to be equally toxic. Science is slow to determine if a new chemical introduced to the market is safe and can replace a regulated chemical.”
And studies have shown that a diet rich in meat, fat, and ultra-processed foods is associated with increased exposures to some phthalates, especially when the foods are obtained away from home, such as fast foods, Peng observed. In addition, some phthalates are added to personal care products such as fragrance.
“As a first step,” she said, “I think reducing consumption of ultra-processed foods packaged in plastics may help reduce phthalate exposure.”
A 2020 report from the Endocrine Society and the International Pollutants Elimination Network (IPEN), entitled, “Plastics, EDCs, and Health” summarizes research on bisphenol A, per- and polyfluoroalkyl substances (PFAS), phthalates, and other EDCs that leach from plastics. The Endocrine Society website also has a link to a 2-page summary.
Levels of 12 Phthalate Metabolites
Previously, the researchers reported how another class of “forever chemicals,” PFAS, were associated with risk of hypertension in a 17-year follow-up of middle-aged women in the SWAN study.
In the current study, they analyzed data from 1308 women in SWAN-MPS who had been recruited at five study sites (Oakland, California; Los Angeles, California; Detroit, Michigan; Pittsburgh, Pennsylvania; and Boston, Massachusetts).
The women were between ages 42 and 52 years in 1996-1997 and self-identified as White, Black, Chinese, or Japanese.
They did not have diabetes in 1999-2000 and had sufficient urine samples for phthalate assessment then and midway through a 6-year follow-up.
The women were a median age of 49 years in 1999-2000. About half were White, 20% were Black, 13% were Chinese, and 15% were Japanese.
Researchers analyzed levels of 12 metabolites, chosen because their parent phthalates have been widely used in industry and commerce, and exposure to these phthalates is a national biomonitoring priority.
The measured phthalates were:
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Three metabolites of low-molecular-weight phthalates:
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mono-ethyl phthalate (MEP)
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mono-n-butyl phthalate (MnBP)
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mono-isobutyl phthalate (MiBP)
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Four metabolites of the high-molecular-weight phthalate di(2-ethylhexyl) phthalate (DEHP), which is of particular public health interest:
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mono(2-ethylhexyl) phthalate (MEHP)
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mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)
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mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
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mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)
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Five metabolites of other high-molecular-weight phthalates
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monobenzyl phthalate (MBzP)
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monoisononyl phthalate (MiNP)
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mono-carboxyoctyl phthalate (MCOP)
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mono-carboxy-isononyl phthalate (MCNP)
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mono(3-carboxypropyl) phthalate (MCPP)
The researchers excluded MiNP from all analyses because it was detected in less than 1% of urine samples.
The different phthalate metabolites were detected in 84.8% of samples (MEHP) to 100% of samples (MnBP and MECPP).
Women who were younger, Black, current smokers, or obese generally had higher concentrations of phthalate metabolites.
Over 6 years, 61 women developed diabetes (an incidence rate of 8.1 per 1000 person-years).
Compared to other women, those with incident diabetes had significantly higher concentrations of all phthalate metabolites except DEHP metabolites and MCPP.
Phthalates were not associated with incident diabetes in Black or Asian women.
However, among White women, each doubling of the concentrations of MiBP, MBzP, MCOP, MCNP, and MCCP was associated with a 30% to 63% higher incidence of diabetes (HR 1.30 for MCNP; HR 1.63 for MiBP).
The SWAN study was supported by the National Institutes of Health (NIH), Department of Health & Human Services, National Institute on Aging (NIA), National Institute of Nursing Research, NIH Office of Research on Women‘s Health, and SWAN Repository. The current study was supported by the National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health, and Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. Peng was supported by an Interdisciplinary Research Training on Health and Aging grant from the NIA. The authors have reported no relevant financial relationships.
J Clin Endocrinol Metab. Published online February 8, 2023. Article
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