Serum levels of phthalate metabolites are linked with the development of type 2 diabetes in the elderly, Swedish researchers found.

“Phthalates are found in numerous household products, such as food packaging, furniture, and toys, and in medical devices, such as tubing and intravenous bags,” researchers P. Monica Lind, PhD, from Uppsala University, and colleagues noted.

After adjustment for sex, diabetes was significantly associated with the presence of monoethyl phthalate (MEP), with an odds ratio of 1.30 (95% CI 1 to 1.69, P=0.049) as well as with detectable monoisobutyl phthalate (MiBP), with an odds ratio of 1.25 (95% CI 1.07 to 1.46, P=0.006), they reported in the June issue of Diabetes Care..

After further adjustment for cholesterol, triglycerides, body mass index, smoking, exercise, and education, MiBP remained significantly related to diabetes (OR 1.30, 95% CI 1.10 to 1.55, P=0.0025), Lind and colleagues they found.

Phthalates also are commonly found in cosmetics and pharmaceutical products, and concerns have been raised about potential adverse health consequences associated with exposure.

Phthalates can bind to certain receptors involved in homeostasis of fats and lipids known as nuclear peroxisome proliferator-activator receptors (PPARs), and PPAR antagonists are used to treat type 2 diabetes.

To explore a possible relationship between these chemical metabolites and diabetes, the investigators analyzed data from a prospective study of 1,016 elderly residents of Uppsala.

They sought to measure serum levels of 10 phthalate metabolites, but only levels of MEP, MiBP, monomethyl phthalate (MMP), and mono(2-ethylhexyl) phthalate (MEHP) were detectable at levels of 0.2 ng/mL in most study participants.

Glucose tests were done after an overnight fast, and diabetes was identified in 119 individuals.

Analysis showed that patients in the highest quintiles of MEP, MiBP, and MMP levels had double or more the risk of diabetes compared with the lowest quintiles, with odds ratios ranging from 2 to 2.50.

But the highest risk was for individuals with MEP in the third quintile (OR 2.87, 95% CI 1.37 to 6.03, P=0.005).

Both MEHP and MiBP had significant associations with elevated proinsulin-to-insulin ratios, while MEP and MMP were related to a high insulin resistance index.

The researchers noted that MEP, MiBP, and MMP all are metabolites of related compounds that are most commonly used in personal care products, while the use of MEPH is primarily to increase the flexibility of plastic.

They hypothesized that the mechanism by which phthalates contribute to diabetes was probably through effects on PPARs.

“Because phthalate metabolites are known ligands to PPARs, receptors known to influence glucose homeostasis, impairments in PPAR-signaling pathways are most likely to contribute to the actions of phthalates on glucose metabolism and diabetes development,” they explained.

Limitations of the study included its cross-sectional design and the measurement of serum, rather than urinary, phthalate metabolites. More metabolites would likely have been detected if urinary measurements had been used, according to the researchers.

In addition, the study population was elderly and white, so the applicability of the findings to other groups is unclear.

Primary source: Diabetes Care
Source reference:  Lind P, et al “Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly” Diabetes Care 2012; 35: 1-6; DOI: 10.2337/dc11-2396.