Insulin-like growth factor-binding protein-1: serum levels, promoter polymorphism, and associations with components of the metabolic syndrome in short subjects born small for gestational age.
BACKGROUND
IGF binding protein (IGFBP)-1 is the only acute regulator of IGF-I bioavailability. Its production is suppressed by insulin, and low levels are associated with hyperinsulinemia and cardiovascular disease risk in adults. Data on IGFBP-1 levels in short, small for gestational age (SGA) subjects are scarce, and associations with IGFBP1 promoter single nucleotide polymorphisms have not been established.


OBJECTIVE
The aim of the study was to determine IGFBP-1 levels in short SGA subjects compared with those in controls, to assess genotype frequency of the -575 G/A single nucleotide polymorphism, and to determine its impact on IGFBP-1 levels.


METHODS
A total of 272 short subjects born SGA and 330 subjects with normal stature (245 children, 85 young adults) participated in the study.


METHODS
We measured fasting levels of IGFBP-1, IGF-I, insulin and lipid parameters, and body composition.


RESULTS
IGFBP-1 sd score (SDS) was comparable to controls in lean, short, SGA children but significantly lower in short SGA adults with normal fat mass (P < 0.001). IGFBP-1 SDS correlated significantly with insulin levels, systolic blood pressure SDS, and various lipid parameters. Baseline IGFBP-1 SDS was lowest in SGA children with -575 GG genotype and significantly higher in SGA children with one or two copies of the A allele. In response to a given insulin level, children with the AA genotype had a significantly higher IGFBP-1 SDS compared to children with the GG genotype.


CONCLUSIONS
Normal IGFBP-1 levels in lean, short, SGA children may reflect a normal metabolic state, despite reported hyperinsulinemia. IGFBP-1 is modulated by polymorphic variability and seems to be an additional player in the complex interaction between the IGF-IGFBP axis, glucose homeostasis, and lipid metabolism.
van der Kaay
Daniëlle
D
Department of Pediatrics, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands.
Deal
Cheri
C
de Kort
Sandra
S
Willemsen
Ruben
R
Leunissen
Ralph
R
Ester
Wietske
W
Paquette
Jean
J
van Doorn
Jaap
J
Hokken-Koelega
Anita
A
D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D001827:Body Height / Q000235:genetics; D002648:Child; D017931:DNA Primers; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011627:Puberty; D012016:Reference Values; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D017931:DNA Primers; D018970:Insulin-Like Growth Factor Binding Protein 1; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I