Relation of cord plasma concentrations of proinsulin, 32-33 split proinsulin, insulin and C-peptide to placental weight and the baby's size and proportions at birth

Small and disproportionate size at birth are associated with type 2 diabetes and coronary heart disease in adult life. Insulin has an important role in controlling growth in utero and we hypothesised that reduced fetal insulin secretion could be one factor underlying these associations. We therefore measured cord plasma concentrations of proinsulin, 32-33 split proinsulin, insulin and C-peptide in 391 babies born at term and related them to the weight of the placenta and to the babies' size and proportions at birth. Babies with a small placental weight and a lower birth weight had lower cord plasma concentrations of split proinsulin and insulin. Babies who were disproportionate, either having a high ratio of head to abdominal circumference or being thin, had lower concentrations of proinsulin, split proinsulin and insulin. The relations with split proinsulin were especially strong, the geometric mean concentration (pmol/l) falling from 14.2 in babies with a head to abdominal circumference ratio of 101.6% or less to 7.2 in those with a ratio above 107.3% (P < 0.0001), and from 17.4 in babies with a ponderal index above 28.5 kg/m(3) to 7.4 in those with a ponderal index of 25.5 kg/m(3) or less (P < 0.0001). These findings support the hypothesis that reduced fetal insulin secretion may be one factor underlying the associations between reduced growth in utero and type 2 diabetes and coronary heart disease in adult life.