The role of the pancreas and insulin secretion in utero is to support fetal growth and preparation of the fetus with the nutritional reserves to maintain glucose homeostasis after birth. Adaptation at birth includes dramatic endocrine changes, up-regulation of enzymes critical for gluconeogenesis and preparation for the infant to regulate glucose control in the setting of an intermittent enteral supply of nutrition. Disorders of glucose homeostasis are not uncommon at this time, particularly in the setting of prematurity and very low birth weight (VLBW<1,500 g). Although historically hypoglycaemia has been the clinical concern, hyperglycaemia is also a well-documented problem, particularly during the first week in VLBW infants. This hyperglycaemia is a marker of insulin resistance and relative insulin deficiency and may reflect the prolonged catabolism observed in VLBW infants. Reduced insulin levels may also contribute to reduced insulin-like growth factor 1 (IGF-1) generation, and an increased risk of retinopathy of prematurity. Pilot studies of insulin replacement in VLBW infants demonstrate improved glucose control, and increased circulating IGF-1 bioactivity. This suggests that, along with nutritional support, restoration of the normal hormonal balance may be important in promoting anabolism in the VLBW infant.