**9. Conclusion**

and waist circumference was found in another cross-sectional study of NHANES data [146]. However, considering the methodological limitations of the existing data, there is no sufficient evidence to conclude there is a correlation between phthalates and diabetes or obesity.

The epidemiological data on BPA and T2DM is less consistent compared with POPs, but is growing. There are two cross-sectional analyses of NHANES data 2003-2008 that reported a positive associations of BPA exposure (median 2.5 and 1.8 µg/l) with self-reported diagnosis of diabetes [125, 147].However,these analyseshave animportantweakness thatlimits theirvalue: the use of a single spot urine sample collected concurrent with the information on diagnosis of diabetes. The single spot sample reflects only recent BPA exposure, so cannot be extrapolated to longerperiod(like years ordecades) which is relevantforthedevelopment ofdiabetes.Other

A closer evaluation of all epidemiological studies on EDCs reveals some weaknesses, such as the assessment of one compound as a surrogate for total mixture (in case of PCBs), the lack of data regarding kinetics, especially on accumulation in lipid-rich tissues (in case of POPs), limited type of biological material used for direct measurement EDCs (serum or urine) or environmental measurement which is not appropriate to calculate the internal dose (in case of As). Other caveats must be considered in the interpretation of studies, such as heterogeneity

There are a number of challenges limiting our understanding of the impact of EDCs on T2DM related to the physical properties of EDCs: the selection of experimental models to assess effects on glucose homeostasis or coexisting risk factors on the exposed individuals included in the

The thousands of chemicals released into the environment create the real scenario of human co-exposure and an enormous analytical challenge in the assessment. Sometimes the physical properties of EDCs such as lipophilicity contribute to their accumulation and persistence in human tissues, even after the exposure has terminated. In this case biomonitoring is the key for the assessment of EDCs. Regarding the types of sample used in analysis, these must be expanded beyond urine and serum to lipid-rich organs (e.g., POPs are accumulated in brain and adipose tissue) as well as tissues relevant to *in utero* and early postnatal stages of exposure (e.g., human breast milk). Also the development of clinical biomarkers it will be useful to

Although environmental and tissue levels of certain EDCs (e.g., PCBs) have declined in some countries in response to EU regulations, they remain of concern in other countries, and

large cross-sectional studies on BPA in China provide conflicting data [148,149].

in the definition of diabetes or insulin resistance.

**8. Challenges in EDCs research**

identify chemically exposed population.

uncertainty still exists regarding future trends.

epidemiological studies.

236 Treatment of Type 2 Diabetes

More studies are necessary to establish the exact mechanisms through which EDCs determine impairments of glucose homeostasis; these studies are imperatively important in order to impose international guidelines that will lead to a reduction of the incidence of T2DM cases induced by chemical exposure.
