Background: In animals, acceleration of neonatal growth is thought to increase the later propensity to insulin resistance and non-insulin-dependent diabetes, whereas slow growth as a consequence of undernutrition is thought to have a beneficial effect. To test this hypothesis in people, we measured fasting concentrations of 32-33 split proinsulin, a marker of insulin resistance, in adolescents born preterm who had participated in randomised intervention trials of neonatal nutrition, and in adolescents born at term.
Methods: We determined fasting 32-33 split proinsulin concentration in participants aged 13-16 years born preterm and randomised to receive a nutrient-enriched or lower-nutrient diet (n=216) or in a reference group born at term (n=61).
Findings: Fasting 32-33 split proinsulin concentration was greater in children given a nutrient-enriched diet (geometric mean 7.2 pmol/L, 95% CI 6.4-8.1) than in those given the lower-nutrient diet (5.9 pmol/L [5.2-6.4]; mean difference 20.6% [5.0-36.3]; p=0.01). Healthy babies born at term had similar fasting 32-33 split proinsulin concentrations (6.9 pmol/L; 6.0-8.2) to the nutrient-enriched group. In non-randomised analyses, fasting 32-33 split proinsulin concentration was associated with greater weight gain the first 2 weeks of life (13.2% [5.4-20.9] change per 100 g weight increase; p=0.001) independent of birthweight, gestation, neonatal morbidity, and demographic, anthropometric, and socioeconomic factors.
Interpretation: Our results suggest that relative undernutrition early in life in children born preterm may have beneficial effects on insulin resistance.