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BPA exposure may alter glucose-stimulated insulin response

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September 26, 2018

Exposure to bisphenol A, or BPA, at a dose deemed safe by U.S. regulatory agencies may change human glucose-stimulated insulin response, according to findings published in the Journal of the Endocrine Society.

“While there has been controversy concerning whether human exposure to BPA is high enough to warrant concern, the exposure models used have been based on the assumption that BPA exposure is almost entirely from food sources, such that BPA would be subjected to extensive first-pass metabolism,” Richard W. Stahlhut, MD, of the division of biological sciences at the University of Missouri-Columbia, and colleagues wrote in the study background. “However, we have shown that transdermal absorption from BPA-coated thermal paper, when enhanced using hand sanitizer, can result in serum levels of bioactive BPA within the range of levels reported in human biomonitoring studies, and that these levels are similar to the ones showing effects in vitro and in animal studies.”

In an exploratory study, researchers conducted two crossover analyses in men and menopausal women. Participants were randomly assigned to BPA at either the first or the second study visit, with a 1-week washout period in between.

During the BPA session, participants were given the maximum safe daily oral BPA dose (50 μg/kg body weight) estimated by the FDA and Environmental Protection Agency. Researchers measured unconjugated BPA and its metabolites, bisphenol glucuronide and bisphenol monosulfate. During the control session, participants were given 1 mL tonic water/15% ethanol solution. Insulin response was assessed in two crossover experiments using an oral glucose tolerance test (n = 8 men) and a hyperglycemic clamp (n = 8; five men).

In both experiments, the participants were assessed for plasma glucose, serum insulin and serum C-peptide at several time points.

Primary outcome was percent change during the BPA session vs. the control session.

The researchers found that after experimental exposure to BPA, participants had serum BPA at levels identified in human biomonitoring studies. In the OGTT experiments, researchers observed a strong, positive correlation between HbA1c and the percent change in the insulinogenic index (Spearman correlation = 0.92), an indicator of early-phase insulin response, and the equivalent C-peptide index (Pearson correlation = 0.97).

In the hyperglycemic clamp study, focusing on the later-phase insulin response to a stable level of glucose, researchers noted that several measures of insulin and C-peptide appeared suppressed during the BPA session relative to the control session. Additionally, the change in insulin maximum concentration was negatively correlated with HbA1c and the maximum concentration of bioactive serum BPA, researchers wrote.

In contrast to the OGTT results, the hyperglycemic clamp results did not demonstrate a significant correlation between HbA1c and the percent change in insulin response between the two sessions, according to researchers. The strongest correlation among these measures was between HbA1c and the percent change in C-peptide area under the concentration-time curve of 70 to 120 minutes (Spearman correlation = –0.66; P = .76).

“The results of our two experiments suggest that oral exposure to the ubiquitous environmental contaminant BPA at the EPA-estimated ‘safe’ daily dose alters the insulin/C-peptide response to a glucose challenge in adults,” the researchers wrote. “Importantly, the effect of BPA on insulin and C-peptide occurred at an internal dose of serum [unconjugated] BPA that could plausibly result from real-world exposures, which for some persons might occur multiple times each day.” – by Jennifer Byrne

Disclosures: The authors report no relevant financial disclosures.