Perinatal 'programming' of insulin resistance in childhood: critical impact of neonatal insulin and low birth weight in a risk population.

Abstract

Low birth weight may predispose to later insulin resistance and hyperinsulinaemia, but the pathophysiological mechanisms are unclear. The perinatal endocrine situation may play an important role, but has been little studied. Children of mothers with diabetes during pregnancy are an important risk population for later insulin resistance and hyperinsulinaemia. We therefore examined relationships between birth weight, insulin and insulin resistance at birth, and insulin secretion and insulin resistance in infancy in these children. We studied 104 infants of mothers with Type 1 diabetes mellitus during pregnancy. Oral glucose tolerance tests (area under the curve of glucose, AUCG) with determination of insulin (area under the curve of insulin, AUCI) were performed at 1-5 years of age. Using correlation and regression analysis, birth data were related to insulin secretion (AUCI) and stimulated insulin/glucose ratio (AUCI/AUCG) in childhood. Children with an AUCI in the highest tertile of distribution had the lowest birth weights. Birth weight was negatively correlated to AUCI in childhood (P = 0.03). Insulin/glucose ratio at birth was raised in infants with an AUCI in the upper tertile, accompanied by a positive correlation between insulin/glucose ratio at birth and AUCI (P = 0.02). Insulin and insulin/glucose ratio at birth were both positively correlated to AUCI/AUCG (P = 0.04 and P = 0.02 respectively), while the correlation between birth weight and AUCI/AUCG was not significant (P = 0.12). In a stepwise regression analysis, insulin/glucose ratio contributed as much as birth weight to AUCI in childhood. Birth weight, however, was significantly negatively related to AUCI/AUCG only when the insulin/glucose ratio at birth was included in the regression model. Insulin and insulin resistance at birth show a positive relation to insulin secretion and insulin resistance in later life, in addition to the influence of a low birth weight, but independent of it. Perinatal and neonatal insulin, known to be of critical importance for long-term outcome, should be evaluated in future studies on the 'small baby syndrome'.