As the tide of chemicals born of the Industrial Age has arisen to engulf our environment, a drastic change has come about in the nature of the most serious public health problems.Rachel Carson, Silent Spring, 1962
Worldwide rates of diabetes and other metabolic diseases have exploded over the last several decades. Globally, more than 170 million individuals currently suffer from diabetes, and this number is projected to reach a staggering 366 million by 2030 (1). This scourge results in significant individual morbidity and mortality while contributing to the economic fragility of healthcare systems across the globe. In the U.S. alone, annual costs associated with diabetes are estimated to be $174 billion (2). As such, every effort must be made to understand the factors underlying this emerging metabolic disaster in order to mitigate its deleterious impact on the individual and society. Recently, an expanding body of scientific evidence has begun to link exposure to synthetic chemicals with a wide variety of diseases, including reproductive tract disorders and neurobehavioral diseases. The present work discusses epidemiological links between chemical exposure and disorders of glucose homeostasis, experimental data demonstrating chemical-induced changes in insulin action, and challenges facing the field of metabolic disruption as well as approaches for addressing those challenges.
Originally articulated in the early 1990s, the environmental endocrine disruptor theory proposes that some exogenous chemicals interfere with endogenous hormonal axes (3). The recognition of this potential mechanism of action was a paradigm shift in toxicology that had previously focused on a chemical’s capacity to induce acute toxicity or to cause cancer via mutagenesis. The Environmental Protection Agency (EPA) defines an endocrine disrupting chemical (EDC) as “an exogenous agent that interferes with the production, release, transport, metabolism, binding, action, or elimination of natural hormones in the body responsible for the maintenance of homeostasis, reproduction, development, and/or behavior” (4). Putative EDCs include structurally diverse chemicals including organic pollutants, heavy metals, pharmaceuticals, and phytochemicals, with humans exposed through agricultural goods and consumer products, as well as water and air contaminated with industrial waste (Fig. 1). Early studies of EDCs focused on identifying chemicals with the capacity to modulate sex steroid and thyroid hormone signaling; however, recent work suggests that some chemicals may disturb signaling pathways critical for energy homeostasis (5). Despite the potential importance of EDCs in the pathogenesis of metabolic diseases, the contribution of synthetic chemical exposure to the diabetes epidemic remains largely unrecognized and underappreciated even though U.S. diabetes rates have increased in concordance with the national production of synthetic organic chemicals (Fig. 2). While such correlations are crude, emerging data supports a biologically plausible causative link between diabetes and chemical exposure. Here, we present data suggesting a role for some synthetic chemicals in the pathogenesis of diabetes that merits comprehensive efforts to address the contribution of environmental pollutants to this burgeoning metabolic catastrophe.