Early Neonatal Events and the Disease Incidence in Nonobese Diabetic Mice

Epidemiologic studies have shown that perinatal events are associated with an increased risk for type 1 (insulin-dependent) diabetes in childhood. We used nonobese diabetic mice to examine whether neonatal separation from the mother with or without phototherapy would affect the incidence of diabetes in this genetically susceptible mouse model. The newborn pups were taken from their mothers for two 4-h periods during each of five successive days. One group of animals was just taken from their mothers and were left lying in daylight in the cage, whereas another group was exposed to identical light as used for treatment of neonatal jaundice in infants. Treatment resulted in a 30% death rate. For animals surviving more than 3 mo the incidence of diabetes was significantly higher in both treatment groups compared with control animals, allowed to stay with their mother. The odds ratio for treatment versus control, stratifying for sex, was 3.42 (95% confidence interval, 1.57-7.74). Histologic insulitis did not differ between treated and untreated animals when examined either at clinical diabetes onset or at 8 mo of age. Blood glucose values at 8 mo of age (in animals without clinical diabetes) did not differ between treated and untreated animals. It is concluded that neonatal separation of the nonobese diabetic mice from their mothers will lead to a significantly increased risk for diabetes. This increase in risk seems to be associated with the induction of metabolic alterations leading to increased peripheral insulin need rather than with an increased rate of β cell destruction.