Aetiology of juvenile-onset diabetes mellitus

Abstract

In Britain the incidence of juvenile-onset diabetes in children appears to be increasing. The incidence in Northamptonshire in 1949 was 1: 7000 children, aged 0- 15 years and a survey of diabetic children of similar age in Sunderland during a ten year period, 1967-76, revealed an incidence of 1: 400. The Sunderland survey comprised ninety-five diabetic children who were divided into three age groups 0-4 years, 5-9 years and 10 - 14 years. Overall more boys than girls develop diabetes, particularly in the younger 0-4 year group but girls increase in number and almost equal boys in the two older groups 5-9 years and 10 - 14 years. The peak age of onset is eight and eleven years, consisting mainly of girls; however, boys predominate at twelve years of age. These peak age ranges related to sex could indicate that the underlying provoking factor in the aetiology of diabetes at these ages may be adrenarche or puberty. Environmental factors also appear to play a role in the aetiology of juvenile-onset diabetes as more diabetic children present with their illness in the winter six months, October to March. This winter onset tendency was more significant in the older children (10 - 15 years), and spatial clustering of the disease in Sunderland children occurred, tending to confirm environmental influences such as infection in the community. Clustering of cases was also related to the highter social class areas of the town, consequently 80% of the diabetic children came from social groups I, II and III. Only 7% of the diabetic children had a first degree insulin dependent diabetic relative compared to the national figure of 11%. A study of the extended family history revealed that almost half the Sunderland diabetic girls and one-third of the boys had a relative with insulin dependent diabetes. The diabetic child with the phenotypes H. L. A. - B8, BW15 and BW18 had a very significant tendency to an extended family history. An analysis of the H. L. A. phenotype showed that 75% of the diabetic children had H. L. A. - B8, BW15 or BW18 phenotype. 53% had H. L. A. - B8 compared to 24% controls. This B8 phenotype accounted for half the children in each of the three age groups. The majority of boys with H. L. A. - B8 presented in the winter six months, whilst girls with this phenotype presented evenly throughout the year. This could suggest that the provoking factor in the aetiology of diabetes in boys with H. L. A. - B8 could be an infection. The H. L. A. - B40 phenotype, not previously associated with a diabetogenic tendency, appears to fall into a similar category to boys with H. L. A. - B8. The height of the diabetic children at the onset of the illness was compared to the height of local children and also to the national centile values. The mean height of the local children (25th centile) was found to be significantly below the national 50th centile. The Sunderland diabetic children were equally distributed about the national 50th centile value and consequently were significantly taller than the local children. Although 80% of the diabetic children were above the local mean height, the diabetogenic phenotypes H. L. A. - B8, BW15 and BW18 were not associated with the very tall diabetic child. Most of the diabetic boys and girls above the 75th height centile had H. L. A. - B7 or B12 phenotypes. If H. L. A. - B8 was combined with either of these two phenotypes the children were shorter in stature. It is possible that the provoking factor in the development of diabetes in boys with H. L. A. - B8 is an infection, whilst diabetes in girls with H. L. A. - B8, BW15 or BW18 appears to be related to puberty or adrenarche. Children with H. L. A. - B7 or B12 may be associated with a different endocrine imbalance producing excessive tallness prior to diabetes becoming evident.