Endocrinology

A healthy 10-year-old boy was admitted to the hospital in diabetic ketoacidosis within three days of onset of symptoms of a flu-like illness. He died seven days later and post-mortem examination showed lymphocytic infiltration of the islets of Langerhans and necrosis of beta cells. Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus. Serologic studies revealed a rise in the titer of neutralizing antibody to this virus from less than 4 on the second hospital day to 32 on the day of death. Neutralization data showed that the virus was related to a diabetogenic variant derived from Coxsackievirus B4. Inoculation of mice with the human isolate produced hyperglycemia, inflammatory cells in the islets of Langerhans and beta-cell necrosis. Staining of mouse pancreatic sections with fluorescein-labeled antiviral antibody revealed viral antigens in beta cells. Both the clinical picture and animal studies suggested that the patient's diabetes was virus induced.

HL-A typing of 150 patients who had developed diabetes mellitus by the age of 30 years showed a significant association with HL-A 8 and W 15. The HL-A genotypes were determined in 17 families in which two or more siblings had this type of diabetes. The zygotic assortment of HL-A haplotypes was found to be significantly disturbed from the expected random pattern, with a reduction in the number of siblings showing no identical haplotypes and an appreciable increase in the number with both haplotypes identical. This appears to be most consistent with the presence of a gene or genes pre-disposing to this type of diabetes at a locus closely linked to the HL-A chromosomal loci. This locus appears to have a fundamental role in the susceptibility to juvenile diabetes.