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

Diabetologia. 2005 Dec;48(12):2609-14. doi: 10.1007/s00125-005-0036-z. Epub 2005 Nov 8.


Aims/hypothesis: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestational-age (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(-1) l(-1), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight / physiology*
  • Blood Glucose / analysis
  • Child, Preschool
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Fasting
  • Female
  • Glucose / pharmacology
  • Glucose Tolerance Test
  • Homeostasis
  • Humans
  • Infant
  • Infant, Low Birth Weight / physiology*
  • Infant, Newborn
  • Infant, Small for Gestational Age / physiology*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin / physiology*
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology
  • Longitudinal Studies
  • Male
  • Prospective Studies
  • Risk
  • Weight Gain*


  • Blood Glucose
  • Insulin
  • Glucose