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Childhood and adolescent exposure to potentially endocrine-disrupting chemicals found in food and drink packaging was associated with obesity and insulin resistance, two groups of researchers reported.

In one study, children with the highest urinary concentrations of bisphenol A (BPA) were twice as likely to be obese compared with those who had the lowest levels (OR 2.01, 95% CI 1.36-2.98, P=0.001), according to Joyce Lee, MD, of the Child Health Evaluation and Research Unit at the University of Michigan in Ann Arbor, and colleagues.

In a second study, each threefold increase in metabolites of di-2-ethylhexylphthalate (DEHP) was linked with an 0.27 (95% CI 0.14-0.40, P<0.001) increase in a homeostatic model assessment of insulin resistance, reported Leonardo Trasande, MD, of New York University's Langone Medical Center in New York City, and colleagues. Both studies appear in the journal Pediatrics.

Bisphenol A has been used to coat metal food containers and in dental sealants and plastic toys, but is no longer permitted in products such as baby bottles following an FDA ban.

Previous research has linked exposure to BPA with diabetes, cardiovascular disease, and obesity in adults, but less is known about the effects of early-life exposures.

To examine this, Lee and colleagues evaluated the relationship between concentrations of BPA in urine with adiposity measures, cholesterol, insulin, and glucose in a population of 3,370 children and adolescents, ages 6 to 18, whose data were available through NHANES (National Health and Nutrition Examination Survey) from 2003 to 2010.

Data gathered included BMI, waist circumference with and without height-ratio, body fat percentage, cholesterol, high-density lipoprotein (HDL) cholesterol, fasting low-density lipoprotein (LDL), fasting glucose, fasting triglycerides, and insulin resistance. The authors pointed out that not all data were available for every individual in the study population, which was a study limitation.

The independent variable was urinary BPA, which was divided into quartiles of less than 1.3 ng/mL, 1.3 to 2.6 ng/mL, 2.6 to 4.9 ng/mL, and greater than 4.9 ng/mL. Measurements were adjusted for age, race, poverty to income ratio, and serum cotinine, which was a proxy for tobacco smoke.

Compared with those with the lowest concentration of urinary BPA, moderate or greater exposure was significantly associated with increased odds of obesity, as reported through 95th or greater percentile of BMI.

Compared with the lowest quartile, there was a 74% increased risk for obesity in the second quartile (OR 1.74, 95% CI 1.17-2.60, P=0.008) and a 64% increase in the third quartile (OR 1.64, 95% CI 1.09-2.47, P=0.02), Lee and colleagues found.

Abnormal waist-to-height ratios also were seen in children in the third (OR 1.41, 95% CI 1.07-1.87, P=0.02) and fourth quartiles (OR 1.55, 95% CI 1.12-2.15, P=0.01) of BPA concentrations.

However, there were no associations seen in the other indicators of cardiovascular disease and diabetes.

Lee's group noted an additional study limitation in the possibility of reverse causality as obese individuals may store BPA differently than nonobese individuals.

In the second study, the authors used data from the 2003 to 2008 NHANES to evaluate associations between metabolites of DEHP, which is often used in plastic food packaging and also in toys and medical devices, with insulin resistance in a group of 5,829 adolescents ages 12 to 19.

Confounders included BMI, calorie intake, tobacco smoke exposure, race, income, and caregiver education.

The association between DEHP and insulin resistance was stronger among girls, Hispanics and blacks, and in households with poverty-income quartiles less than 1.3.

Those with the highest concentrations of urinary DEHP had a 21.6% prevalence of insulin resistance (95% CI 17.2–26, P=0.017).

Median HOMA-IR was 2.24 (SE 0.15, IQR 1.43-3.66), and 17.6% were insulin-resistant (HOMA-IR ≥4.39). Six reported diabetes diagnosed by a doctor and three reported physician-diagnosed prediabetes.

The group noted that the associations persisted despite controlling for BPA, but that HOMA-IR and insulin resistance "were not signiﬁcantly associated with metabolites of lower molecular weight phthalates commonly found in cosmetics and other personal care products."

In an accompanying editorial, Robert Brent, MD, PhD, of the Alfred I. DuPont Hospital for Children in Wilmington, Del., noted that use of urinary plasticizer concentration as a surrogate measure of environmental exposure may not hold much water.

"Most BPA articles in humans use the urine content of BPA as a surrogate of exposure, when in reality it is a measure of the intake of BPA from diet," he noted, adding that "actual serum levels are extremely low and in many instances not detectable."

Referencing previous research, he also cautioned that urine markers were "not necessarily reflective of a significant exposure" and that "readers should use caution in interpreting more than the data actually indicate."

Dana Boyd Barr, PhD, of the Department of Environmental Health at Emory University in Atlanta, disagreed, arguing that the studies presented solid preliminary data.

"We've long thought that some of these chemicals were related to obesity and perhaps to insulin resistance change, but this is some of the first evidence linking those exposures to the outcome," Barr told MedPage Today.

Lee's group called for "longitudinal studies to conﬁrm a possible causal association between BPA and excess body fat."

Trasande and colleagues noted that "knowledge gaps ... persist in understanding food contamination with DEHP."

But Trasande's group also pointed out that "alternatives to DEHP include wax paper and aluminum wrap; indeed, a dietary intervention that introduced fresh foods that were not canned or packaged in plastic reduced DEHP metabolites by 53% to 56%."