Genes are not only responsible for static, inherited characteristics such as eye color; they also guide how cells function throughout life. Genes carry the instructions that our cells use for making proteins, and it is these proteins that carry out most of the functions of the cell. The cells in our bodies contain the same genes, yet these cells may have vastly different functions. For example, the beta cells in the pancreas make the protein hormone insulin (at least, in people who do not have type 1 diabetes); cells called lymphocytes make antibodies. These differing functions depend on which genes are "switched on" in that cell type. The cell's job, based on that switching on or off, is called "gene expression." Cells differ, then, not because they contain different genes (they don't), but because they express genes differently. Whether a gene is switched on or off can depend on the type of cell, its surroundings, its age, and external signals (Alberts et al. 1998). 

Each person's DNA sequence differs slightly from other people's. DNA sequence can affect gene expression and gene function, and contribute to a person's susceptibility to various diseases. Changes in gene expression can result from changes to the DNA sequence (mutations are one example of changes to DNA sequence). Changes in gene expression can also result from epigenetic changes, which are changes in gene function that do not involve changes to the DNA sequence. These changes involve alterations in proteins that "package" the DNA in our cells (Hewagama and Richardson 2009).

Health and disease are determined by interactions between our genes and the environment. Researchers are looking into how environmental factors can affect how genes guide the function of cells (gene expression), and how this process can lead to disease. Metabolism is one example of this process. In animals, the mother's diet during gestation helps to determine the metabolism of the offspring later in life. The offspring may be more likely to be obese, for example, as well as have epigenetic changes in their genes that control metabolism. A study in humans has found that a large portion of a person's metabolic disease risk (obesity and type 2 diabetes are metabolic diseases) is determined by the prenatal environment, and associated with certain epigenetic changes (Godfrey et al. 2011). 

In a review of how environmental contaminants can affect gene expression, Edwards and Myers (2007) point out that chemically induced changes in gene expression are associated with a variety of diseases, including diabetes. Some of these changes occur early in development, e.g., in utero, possibly contributing to disease later in life. Contaminant exposures may contribute to disease depending on genetic background, developmental stage, timing, duration, and interactions of mixtures of contaminants. One chemical may have multiple mechanisms of action, and individuals may have differing sensitivities to exposures depending on their genetic background (Edwards and Myers 2007).

 

Scientists have shown that many chemical exposures can lead to epigenetic changes. They have also found similar or the same epigenetic changes in people suffering from certain diseases. Whether these exposures actually lead to disease via these epigenetic changes remains to be determined (Baccarelli and Bollati 2009).

 

Contaminants considered here that have been found to affect gene expression include arsenic, bisphenol A, some persistent organic pollutants, phthalates, some heavy metals, trichloroethylene, and air pollutants (most of these are reviewed in Baccarelli and Bollati 2009).

What might epigenetic processes have to do with type 1 diabetes?  Epigenetic variations are associated with the development of type 1 diabetes (Rakyan et al. 2011). There is evidence that environmental factors can modify the immune system via epigenetic mechanisms to cause the autoimmune disease lupus (SLE). This evidence raises the possibility that epigenetic processes may also contribute to the development of type 1 diabetes and other autoimmune diseases via their effects on autoimmunity (Hewagama and Richardson 2009).

 

MacFarlane et al. (2009) propose a number of possible ways that epigenetic processes could influence the development of type 1 diabetes. For example, epigenetic mechanisms can influence not only the immune system, but also beta cell development, maintenance, and regeneration. Planas et al. (2010) discuss gene expression changes in type 1 diabetes. In the pancreas, there is overexpression of inflammatory immune response genes. There is some consistency of gene expression changes in people with various autoimmune diseases; these changes largely affect the immune system these diseases, affecting differing target organs (the target organ in type 1 is the pancreas).

 

Both nutrition and environmental contaminants can affect epigenetic processes. Lee et al. (2009) propose that researchers consider both of these factors in tandem, since many chemicals contaminate food items. They also propose that epigenetic mechanisms may be involved in the associations between persistent organic pollutants (POPs) and type 2 diabetes. Two recent studies have found human evidence that certain epigenetic changes are associated with levels of POPs, at both high levels of exposure (Rusiecki et al. 2008) and at low levels (Kim et al. 2009). These specific changes are not necessarily related to diabetes development, but do provide evidence that POPs can affect epigenetic processes.

Epigenetic changes induced by embryonic exposure to a pesticide, including immune system abnormalities, were transmitted across four generations in rats (Anway et al. 2006). Epigenetic changes that are passed to the next generation have been proposed as one of the processes leading to the development of type 2 diabetes (Portha 2005). If contaminants or other environmental factors can result in epigenetic changes in humans that can be passed down to subsequent generations, the implications are daunting. Curiously, epigenetic changes may also be able to skip a generation. And yet, there is also evidence that epigenetic changes can be erased from one generation to the next, probably depending on genetic background, gender, age, diet, duration of exposure, and timing. Little is known about persistent exposures over multiple generations, how epigenetic changes could be reversed, or when they might be permanent (Gabory et al. 2009).

 

Animal studies have found that if a mother animal has diabetes, her offspring will have disturbed beta cell function, and may become obese. In humans, children born to mothers with diabetes (type 1 or 2) may be more susceptible to diabetes and obesity later in life, although not all studies have supported this finding (Poston 2010).

The debate is not genes versus the environment anymore. Now, we wonder how the environment can affect how genes control the function of cells (gene expression). Some environmental exposures can affect gene expression through epigenic or other processes. Whether these processes are involved in type 1 diabetes development is not known, but deserves further study. The possibility that these changes can be passed down from one generation to the next has profound implications.