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Potential Mechanisms


Amy has had type 1 diabetes for 25 years. She has just written a book, A Smart Woman's Guide to Diabetes, Authentic Advice on Everything from Eating to Dating to Motherhood.
We do not know how exactly type 1 diabetes develops, but a variety of biological mechanisms may be involved. We also do not know the precise mechanisms by which environmental factors may act to influence disease. But researchers are working to elucidate the mechanisms behind both of these processes.

Is it increased initiation or faster progression?

One of the debates in the scientific literature is whether the rising incidence of type 1 diabetes in children is due to increased disease initiation, a faster disease progression, or both. Disease initiation essentially means the appearance of certain autoantibodies, considered the "triggering" of autoimmunity. These antibodies may appear early in life or even in the womb, with type 1 diabetes developing more than a decade later (Narendran et al. 2005), which is where disease progression comes in. Disease progression essentially means the loss of beta cell function over time (Tsai et al. 2006). While we know that type 1 diabetes incidence is increasing in children, it is not entirely clear whether incidence is also increasing in adults. Is the disease simply appearing at a younger age, in children who otherwise would have gotten it as adults? Can this possibility account for the increasing incidence in children? Researchers have long suspected that environmental factors operating during gestation and early life may lead to the development of the disease by triggering autoimmunity. Yet factors that can accelerate the progression of the disease may also contribute to the increasing incidence at younger ages (Gale 2005b).
 
An interesting example from Finland and Russia helps to illustrate this point. In an area where genetic background is similar, the more affluent Finns have a six times higher incidence of type 1 diabetes than do the Russians living on the other side of the border. Yet a recent study has found that the presence of type 1 diabetes associated autoantibodies was just as high in Russian children as in the Finns. Autoimmunity, then, was "triggered" in both populations, but more Finns ended up with diabetes than did Russians. This and other studies support the idea that a more rapid disease progression plays a more important role in the increasing incidence of type 1 diabetes in children than does the initiation of autoimmunity (Kondrashova et al. 2007). Another study that compared two groups of children genetically at risk of type 1 found those born earlier had a similar rate of diabetes related autoantibodies, but developed the disease slower than those born more recently. This finding suggests that the increasing incidence of type 1 in children could be due to factors that fail to control the autoimmune attack properly (Ziegler et al. 2011).