Parents of children with newly diagnosed Type 1 diabetes invariably want to know why their children developed diabetes. On many occasions, several newly diagnosed patients actually live in the same neighborhoods, prompting families to wonder if there is something in the environment responsible for causing diabetes. At present the working theory is that Type 1 diabetes is caused by a combination of two factors. (1) A genetic predisposition or risk (low, moderate, high) for the possibility of the development of Type 1 diabetes that is located in HLA region of chromosome six and (2) a trigger that causes the killer T cells to attack the beta islet cells of the pancreas. We currently believe that infections (i.e. mumps, rubella, coxsackie b virus, and influenza) are one type of trigger based on extensive, evidence-based research.
The authors of a recent study looked at the presence of temporal clustering of new cases of diabetes in which a causal agent could be responsible for the association.
(Muirhead CR, Cheetham TD, Court S, Begon M, McNally RJQ (2013) How Do Childhood Diagnoses of Type 1 Diabetes Cluster in Time? PLoS ONE 8(4): e60489. doi:10.1371/journal.pone.0060489). The authors, located in England, decided to perform the study after noting a general “irregular temporal distribution of cases of Type 1 diabetes in children.” According to the authors a “general irregular temporal distribution of cases that is not confined to one particular time period is known as temporal clustering. As such, temporal clustering may provide further evidence that T1DM has an infectious or local environmental component.”
Who were the study participants? The study looked at data for children aged 0-14 who were diagnosed with diabetes between 1/1/90 and 12/31/2007 who resided in a region of northeast England. The authors used influenza as a positive control, using the same methodology to analyze the data from their study.
What were the results?
- A clear, long-term cyclical pattern was noted (statistically significant)
- A temporal clustering of cases occurs over periods of a few months, in addition to cyclical variation over years (statistically significant)
How does one interpret these results?
According to the authors, this pattern of occurrence is consistent with the involvement of exogenous agents, such as infection, that may demonstrate epidemicity. The control, influenza infection, was also noted to demonstrate temporal clustering at levels of months, quarters of a year, and flu seasons. Several referenced studies have reported “seasonality” in dates of diagnosis of pediatric Type 1 diabetes, noting peaks in October to January and valleys in June to August for Diabetes Centers in the Northern Hemisphere. Other studies suggest that the seasonal pattern might change over time. Thus, this study adds additional evidence for the irregular temporal pattern or temporal clustering.
As we note the increased incidence of Type 1 diabetes, it is clear that genetic susceptibility is clearly not the only factor; indeed factors such as disease clearly may play a role. Thus, according to the authors, the finding of such an irregular pattern in incidence is consistent with the involvement of an infectious agent which
“itself displays an irregular pattern in the environment. Existing evidence for role of infections as an etiology of Type 1 diabetes is noted in multiple epidemiologic studies that include birth order, interbirth interval, rural locality, population mixing, day care attendance, and recorded neonatal illnesses.” The evidence in the present study in which temporal clustering over a few months period strongly suggests that an infectious agent may act as the final trigger in the development of T1DM.
The authors note that the type of clustering found in their study suggests that the underlying pattern in “the risk of such an agent being passed from a reservoir host may exhibit a natural epidemicity.” They go on to suggest that the most common type of reservoir for in temperate regions is the wild rodent population.
I have discussed the “hygiene hypothesis” in the past (greater disease incidence with improved sanitation resulting in an autoimmune attack). Timing of disease exposure may also play a major role, given that certain viruses might trigger autoimmunity when infection occurs later, but protective when infection occurs earlier.
In summary, this paper suggests that “a precipitating agent or agents” that trigger diabetes may be the result of an infection that occurs in “mini-epidemics.”
Published On: July 18, 2013