Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children

Abstract

Aims/hypothesis: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestationalage (SGA) at birth may be a consequence of rapid early postnatal weight gain. Materials and methods: We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). Results: Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol, p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). Conclusions/interpretation: SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.

Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants

“…Reduced insulin sensitivity in SGA born infants can already be demonstrated in early childhood (5,7). In the present study, we showed that at 1 y of age term born SGA children have a high prevalence of high triglycerides, with the cut-off value based on term born AGA children from the same population.…”

“…This is based on the studies of Barker et al (1), who first indicated the importance of fetal growth for development of the metabolic syndrome in adulthood and showed an increasing prevalence with decreasing birth weight. Not only term smallfor-gestational-age (SGA) born infants, but also preterm born infants have an increased prevalence of several components of the metabolic syndrome, already in childhood (2)(3)(4)(5)(6)(7)(8)(9). The relation between metabolic syndrome components in childhood and fetal growth was studied by Jaddoe et al (10); they showed that first trimester fetal growth restriction is associated with an adverse cardiovascular risk profile at 6 y of age.…”

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective

“…However, it is a less satisfactory explanation for variation across the normative range and in any event insulin resistance does not develop until well after birth. 59 We 3 and Bateson 60 independently proposed an extension of this line of argument, suggesting that these relationships are responses to variation within the anticipated range of early developmental environments and involve the physiological processes of developmental plasticity rather than the pathological processes of developmental disruption. In particular, both of us proposed an anticipatory model based on the considerable comparative evidence that organisms in early development may make adaptive responses which are of no advantage at the time they are made but are able to better match the organism to the later predicted environment.…”

Fetal programming of glucose–insulin metabolism

“…More recently a study of small for gestational age infants (SGA) and appropriate for gestational age infants (AGA) showed increased insulin sensitivity at birth in (SGA) infants, which could potentially drive their rapid postnatal catch up growth. By 3 years of age (SGA) offspring were more insulin resistant than (AGA) offspring however (14).…”