Bisphenol A and Type 2 Diabetes Mellitus: A Review of Epidemiologic, Functional, and Early Life Factors

Abstract

Type 2 diabetes mellitus (T2DM) is characterised by insulin resistance and eventual pancreatic β-cell dysfunction, resulting in persistent high blood glucose levels. Endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) are currently under scrutiny as they are implicated in the development of metabolic diseases, including T2DM. BPA is a pervasive EDC, being the main constituent of polycarbonate plastics. It can enter the human body by ingestion, through the skin, and cross from mother to offspring via the placenta or breast milk. BPA is a xenoestrogen that alters various aspects of beta cell metabolism via the modulation of oestrogen receptor signalling. In vivo and in vitro models reveal that varying concentrations of BPA disrupt glucose homeostasis and pancreatic β-cell function by altering gene expression and mitochondrial morphology. BPA also plays a role in the development of insulin resistance and has been linked to long-term adverse metabolic effects following foetal and perinatal exposure. Several epidemiological studies reveal a significant association between BPA and the development of insulin resistance and impaired glucose homeostasis, although conflicting findings driven by multiple confounding factors have been reported. In this review, the main findings of epidemiological and functional studies are summarised and compared, and their respective strengths and limitations are discussed. Further research is essential for understanding the exact mechanism of BPA action in various tissues and the extent of its effects on humans at environmentally relevant doses.

Keywords: beta cell; bisphenol A; endocrine disruptors; type 2 diabetes.

Figure 1

Overview of the adverse metabolic effects of BPA at the foetal, neonatal, and adult stages. HFD—high fat diet. TG—triglycerides. HDL-C—high density lipoprotein cholesterol.

Figure 2

Diagram summarizing the key pathophysiological mechanisms linking BPA to T2DM. BPA acts in pleiotropic ways to impact on the main tissues that regulate glucose homeostasis. In the pancreas, it can modulate insulin production positively or negatively to differentially alter the early and late phases of GSIS. BPA affects insulin sensitivity and insulin receptor signalling in the muscle and liver, increases de novo lipogenesis, reduces the release of adiponectin, and alters central feeding behaviour through multiple pathways. GSIS—glucose-stimulated insulin secretion. NPY—neuropeptide Y. POMC—proopiomelanocortin.