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The inability to regulate blood glucose concentration (BG) is a common complication of prematurity and stress in neonatal intensive care, particularly in very low birth weight (VLBW) neonates. Model-based glycaemic control requires quantification of glucose and insulin appearance, clearance, and action. In the VLBW neonates plasma insulin concentration is often used to reflect insulin secretion due to sampling limitations. In this study, C-peptide concentrations are used to more accurately analyse insulin secretion in a VLBW neonatal cohort, and a comparison of insulin secretion and sensitivity is made between male and female sub cohorts. The retrospective analysis is made of a cohort comprises 88 extremely pre-term (median age 26 [25–27] weeks) and very low birth-weight infants (median birth weight 793 [691-901 g]). In 41 of the infants, C-Peptide plasma concentrations were used in conjunction with C-peptide models to estimate insulin secretion. Time varying model-based insulin sensitivity values are also fit across dense clinical data from the entire 88 patients. Female infants had higher insulin secretion than males (P