Urinary concentrations of two chemicals commonly found in food packaging — bisphenol A (BPA) and di-2-ethylhexyl phthalate (DEHP) — were associated with risks for obesity in children and insulin resistance in teens, two studies showed.

In one study, greater urinary concentration of BPA, commonly found in food and drink packaging, was significantly associated with higher risk of body mass index (BMI) in the 95th percentile or greater, as well as greater odds of an abnormal waist circumference-to-height ratio, according to Joyce Lee, MD, of the Child Health Evaluation and Research Unit at the University of Michigan in Ann Arbor, and colleagues.

Another study of adolescent exposure to the plasticizer di-2-ethylhexyl phthalate (DEHP) showed that each three-fold increased concentration of the chemical in urine was associated with a 27% increased risk for 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.

DEHP is another chemical compound found in plastics used in the manufacture of food and drink containers.

In July 2013, the FDA issued a ban on BPA in infant formula packaging.

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.

By quartile, this was associated with a 74% increased odds among those in the second quartile (odds ratio 1.74, 95% CI 1.17-2.60, P=0.008), 64% increase odds among those in the third quartile (OR 1.64, 95% CI 1.09-2.47, P=0.02), and a two-fold increased risk among those with the highest urinary BPA concentration (OR 2.01, 95% CI 1.36-2.98, P=0.001).

Those 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 concentration were significantly more likely to have an abnormal waist circumference-to-height ratio.

There were no associations seen in the other indicators of cardiovascular and diabetes health, findings that contrast “with adult studies that have linked BPA levels with cardiovascular disease and diabetes,” the authors acknowledged.

Lee’s group pointed out some other study limitations including the chance for reverse causality as obese individuals may store BPA differently than nonobese individuals.

In the study by Trasande and colleagues, the authors used data from the 2003 to 2008 NHANES to evaluate associations between metabolites of DEHP with continuous and categorical measures of homeostatic model assessment of insulin resistance (HOMA-IR) through a population of 5,829 adolescents, ages 12 to 19.

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

For each log unit increase in DEHP metabolites, there was a 0.19 increase in score for homeostatic model assessment of insulin resistance (P=0.005). This association 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 on insulin resistance (95% CI 17.2%-26.0%,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 prediabetes as diagnosed by a physician.

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.”

Lee’s group’s called for “longitudinal studies to confirm a possible causal association between BPA and excess body fat,” while Trasande’s group pointed out that “knowledge gaps … persist in understanding food contamination with DEHP … although further studies are needed, it should be noted that alternatives to DEHP include wax paper and aluminum wrap; indeed, a dietary intervention that introduce fresh foods that were not canned or packaged in plastic reduced DEHP metabolites by 53% to 56%.”

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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