The Rising Incidence of Childhood Type 1 Diabetes and Reduced Contribution of High-Risk HLA Haplotypes 

Gillespie KM, Bain SC, Barnett AH, Bingley PJ, Christie MR, Gill GV, Gale EAM. Lancet. 2004;364:1699-1700.

Since the 1950s, the incidence of childhood-onset type 1 diabetes has risen, particularly in children under 5 years of age. The purpose of this study was to determine if the genetic susceptibility of the type 1 diabetes population has also changed over the past 50 years.

The genetic risk of type 1 diabetes is related to a hierarchy of HLA haplotypes, with age of onset being inversely related to the proportion of HLA high-risk susceptibility haplotypes. In this study, the frequency of HLA haplotypes of 2 cohorts were compared: an older-age cohort consisting of 194 subjects diagnosed with childhood-onset type 1 diabetes >50 years ago (between 1922 and 1946), and a younger-age cohort, consisting of 582 age- and sex-matched subjects diagnosed with childhood-onset type 1 diabetes within the last 10 years (between 1985 and 2002).

Results showed that the frequency of patients with the highest risk genotype has decreased while the frequency of patients with lower-risk genotypes has increased. The overall frequency of high-risk HLA haplotypes was 47% in the older cohort and 35% in the younger cohort. Of subjects diagnosed under the age of 5 years, 63% of the older cohort and 42% of the younger cohort were found to have a high-risk HLA haplotype.

The researchers concluded that the increasing incidence of childhood-onset type 1 diabetes is due to an environment that has become increasingly conducive to diabetes development among genetically susceptible individuals. In a commentary on the article also published in the November 6 2004 issue of Lancet,[1] Marian Rewers and Paul Zimmet emphasize that although the contribution of environmental factors to the development of childhood type 1 diabetes is widely accepted, there is still little evidence as to what these causative factors are.

Reference

1. Rewers M, Zimmet P. The rising tide of childhood type 1 diabetes—what is the elusive environmental trigger? Lancet. 2004;364:1645-1647.