OXFORD, England Diabetes mellitus type I has an apparent seasonal pattern, possibly suggesting a viral cause, according to a recent British study.
Peter M. Rothwell, MD, clinical lecturer in the department of clinical neurology at Radcliffe Infirmary here, and his colleagues reported that children who have diabetes are more likely to be born in the spring or early summer than children without the condition, which is consistent with a viral cause. The study was reported in the British Medical Journal.
"There is an increasing awareness of the fact that the environment early in life causes disease later in life," Rothwell said.
Rubella is a prime example of the impact a maternal viral infection may have on a fetus.
"Congenital rubella syndrome is a known cause of diabetes," Rothwell said. "It has been recognized that children with congenital rubella syndrome have a 20 times greater risk of having diabetes. Today, because of immunization it has virtually disappeared, but the link with diabetes was fairly well-established. That is a specific example. If rubella causes diabetes, one may find another virus causing it as well."
If insulin-dependent diabetes is, in fact, caused by in utero exposure to a viral infection, birth dates of children with diabetes should also show seasonal peaks.
The researchers reviewed registries of children with insulin-dependent diabetes born between 1974 and 1988 in three areas England and Wales, Scotland and Yorkshire. The study included 2,258 children in the Scottish registry; 1,142 in the Yorkshire registry; and 1,265 in the registry for England and Wales.
In each area, significantly more children with diabetes were born between March and June compared with the general population; fewer children with diabetes were born during the winter months.
"Our study has shown abnormal seasonality of birth in three large independent populations with childhood onset diabetes," the researchers concluded in their study. "This is unlikely to be due to chance, and it is difficult to conceive of a bias that might account for the results. ... As seasonality of birth cannot be accounted for by genetic mechanisms, environmental factors must be important in the etiology of diabetes. Second, to induce seasonality of birth these environmental factors must exert their influence in utero or in the first year of life. Third, these environmental factors must, of course, be seasonal in nature. Our observations are consistent with the hypothesis that the disease process resulting in childhood diabetes is initiated by a viral infection early in life."
Although the evidence so far apparently points to a viral influence, it is much too soon to pinpoint which virus if any may be the causative agent.
"It may be another environmental agent, but it is most likely a virus," Rothwell said.
An earlier case-control study implicated coxsackievirus as a factor in diabetes, he said. In that study, blood samples taken during pregnancy found an increased prevalence of coxsackievirus antibodies in samples from women whose children went on to develop diabetes, suggesting prenatal exposure.
Another case-control study discovered that adolescents with diabetes had higher rates of IgM antibodies for enteroviruses compared with adolescents without diabetes (Infectious Diseases in Children. 1994; 7(11):4).
Rothwell's hypothesis is consistent with the fact that diabetes mellitus, which is usually caused by a dysfunctional immune system that attacks islet cells in the pancreas, tends to run in families.
"With all autoimmune diseases, there are genetic and environmental factors," Rothwell said. "The disease is caused by some sort of environmental agent, but whether it causes disease depends on how the person's immune system reacts, and how the immune system reacts is determined by genes."
Rothwell's next step is to examine birth rates in other countries for similar seasonal patterns and to determine if similar patterns are present among adults with diabetes. He expects to find the seasonal pattern only among children and adolescents; adult-onset diabetes may be caused by a variety of factors.
Diabetes mellitus type I, or insulin-dependent diabetes, is associated with decreased insulin production and is the most common form of diabetes in people younger than 40 years. The condition develops gradually, with symptoms often not appearing until 90% or more of the islet cells have been damaged.
Studies of twins highlight the dual influence of genetic and environmental factors. Between 35% and 50% of identical twins develop diabetes after the first twin develops the disease. Although this suggests a genetic link, the fact that at least half of the twins do not develop diabetes indicates that other factors must also have an affect. If the condition was strictly genetic, all of the twins would develop the disease.
For more information, see:
- Rothwell PM, Staines A, Smail P, et al. Seasonality of birth of patients with childhood diabetes in Britain. Br Med J. 1996; 312:1456-57.
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