High levels of phthalates can lead to greater risk for type-2 diabetes - April 12, 2012

[John]

Uppsala University

High levels of phthalates can lead to greater risk for type-2 diabetes

[Published 2012-04-12]

There is a connection between phthalates found in cosmetics and plastics and the risk of developing diabetes among seniors. Even at a modest increase in circulating phthalate levels, the risk of diabetes is doubled. This conclusion is drawn by researchers at Uppsala University in a study published in the journal Diabetes Care.
 
“Although our results need to be confirmed in more studies, they do support the hypothesis that certain environmental chemicals can contribute to the development of diabetes,” says Monica Lind, associate professor of environmental medicine at the Section for Occupational and Environmental Medicine, Uppsala University.
 
Together with Lars Lind, professor of medicine at Uppsala University, she has analysed new information from the so-called PIVUS study, which covers more than 1 000 70-year-old women and men in Uppsala.
 
In a physical examination participants were examined for fasting blood sugar and various insulin measures. They submitted blood samples for analysis of various environmental toxins, including several substances formed when the body breaks down so-called phthalates. Most people come into daily contact with phthalates as they are used a softening agents in plastics and as carriers of perfumes in cosmetics and self-care products.
 
As expected, diabetes was more common among participants who were overweight and had high blood lipids. But the researchers also found a connection between blood levels of some of the phthalates and increased prevalence of diabetes, even after adjusting for  obesity, blood lipids, smoking, and exercise habits. Individuals with elevated phthalate levels had roughly twice the risk of developing diabetes compared with those with lower levels. They also found that certain phthalates were associated with disrupted insulin production in the pancreas.
 
“However, to find out whether phthalates truly are risk factors for diabetes, further studies are needed that show similar associations. Today, besides the present study, there is only one small study of Mexican women. But experimental studies on animals and cells are also needed regarding what biological mechanisms might underlie these connections,” says Monica Lind.
 
Facts about phthalates:   
Mono-methyl phthalate (MMP), Mono-ethyl phthalate (MEP) and mono-isobutyl phthalate (MiBP) are all metabolites of the chemicals dimethylphthalate (DMP), Diethyl phthalate (DEP) and Di-isobutyl phthalate (DiBP), respectively, and are used in, among other things, cosmetics, self-care products, solid air fresheners, and scented candles. DMP is also used in ink and as a softening agent in cellulose plastics.
 
For more information, please contact Monica Lind, tel: +46 (0)18-611 9745; mobile: +46 (0)70-320 30 66, e-mail: Monic...@medsci.uu.se
 
P Monica Lind, Björn Zethelius, and Lars Lind, Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly, Diabetes Care

Abstract of Study:

Circulating Levels of Phthalate Metabolites Are Associated With Prevalent Diabetes in the Elderly

1. P. Monica Lind, PHD¹⇓,
2. Björn Zethelius, MD, PHD²,³ and
3. Lars Lind, MD, PHD⁴

+ Author Affiliations

1. ¹Department of Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
2. ²Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden
3. ³Medical Products Agency, Uppsala, Sweden
4. ⁴Department of Medicine, Uppsala University Hospital, Uppsala, Sweden

1. Corresponding author: P. Monica Lind, monic...@medsci.uu.se.

Abstract

OBJECTIVE Phthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome proliferator–activated receptors (PPARs). Because PPAR-γ agonists modulate insulin sensitivity and are used to treat type 2 diabetes, we investigated whether circulating levels of phthalate metabolites are related to prevalent type 2 diabetes.

RESEARCH DESIGN AND METHODS A total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer. Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a fasting plasma glucose >7.0 mmol/L.

RESULTS A total of 114 subjects were shown to have diabetes. Following adjustment for sex, BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01), monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05), but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence of diabetes. Using the fasting proinsulin–to–insulin ratio as a marker of insulin secretion and the homeostasis model assessment-insulin resistance index as a marker of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas MEP and MMP mainly were related to insulin resistance.

CONCLUSIONS The findings in this cross-sectional study showed that several phthalate metabolites are related to diabetes prevalence, as well as to markers of insulin secretion and resistance. These findings support the view that these commonly used chemicals might influence major factors that are regulating glucose metabolism in humans at the level of exposure of phthalate metabolites seen in the general elderly population.

• Received December 9, 2011.
• Accepted March 2, 2012.

• © 2012 by the American Diabetes Association.

[John]