Low nutrient intake and early growth for later insulin resistance in adolescents born preterm

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% Cl 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 in 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.