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


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
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.
Mericq
V
V
Institute of Maternal and Child Research, University of Chile, Santiago, Chile. vmericq@med.uchile.cl
Ong
K K
KK
Bazaes
R
R
Peña
V
V
Avila
A
A
Salazar
T
T
Soto
N
N
Iñiguez
G
G
Dunger
D B
DB
D001724:Birth Weight / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007223:Infant; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012306:Risk; D015430:Weight Gain
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose