Nowadays, it is agreed that childhood type 1 diabetes is a progressively developing disease in which the clinical unmasking is usually triggered by an infectious (viral) disease, oftentimes during the yearly viral epidemic in autumn and winter (1). The timing of the onset of the autoimmune process and its initiating factor(s) are uncertain and controversial. One of the proposed mechanisms is that viruses damage the pancreatic β-cells and trigger the autoimmune process (2), which, by subsequent destruction at a loss of 70–80% of β-cells, causes the clinical disease.
Epidemiological studies performed by Z.L. and I.A. in recent years in Israel (3), Sardinia (4), Slovenia (6), and parts of Germany (7) have revealed that children and adolescents who developed type 1 diabetes at various ages have a statistically significant different pattern in their seasonality of month of birth from that found in the total live births for the respective country. Children who developed diabetes had an excess birth rate in spring and summer months compared with an evenly distributed birth rate in the general population. It was proposed that in pregnancies starting in autumn and early winter, periods of the yearly viral epidemics, the mother transmits to the fetus β-cell pathogenic viruses, which in genetically susceptible individuals initiate the autoimmune process.
To test this hypothesis, the seasonality of the month of birth of 61 offspring of type 1 diabetic parents (mothers and/or fathers) who were found to be IAA/GAD-positive were compared with 1,754 offspring without antibodies. All of the babies from the German BABYDIAB Study were tested within the first year of life, and testing was repeated at 2, 5, 8, and 11 years (8). The data of the children in the two groups were divided into the four 3-month seasonal periods of the year, which were compared using Student’s t test between the pooled means (±SD) for each seasonal block.
The month of birth of the antibody-positive offspring showed a significantly different month of birth pattern (P < 0.03), which peaked between June and September, from the antibody-negative offspring.
The present findings strengthen the previous epidemiological observations that children who develop autoimmune diabetes have a different seasonality pattern than the general population (3,4,5,6,7) and fit the viral etiology theory (2). Recently, further support is provided by the findings of Lonnrot et al. (9) who sampled sera every 6 months from 765 originally nondiabetic siblings of type 1 diabetic children and found that 22% (11 of 49) of those who subsequently developed the clinical disease had enterovirus RNA in their sera compared with 2% (2 of 105) of control subjects. At clinical manifestation, all of the children were negative for enterovirus RNA.
In conclusion, the present observations support the hypothesis that the autoimmune process begins in utero or in the perinatal period in many children and adolescents who develop type 1 diabetes.
References
Address correspondence to Prof. Zvi Laron, Endocrine and Diabetes Research Unit, Schneider Children’s Medical Center, 14 Kaplan St., 49202 Petah Tiqva, Israel. E-mail: [email protected].
