Intrauterine Growth Retardation and Consequences for Endocrine and Cardiovascular Diseases in Adult Life: Does Insulin-Like Growth Factor-I Play a Role?

Abstract

Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th gestational week, and rises gradually during pregnancy where it replaces pituitary GH in the maternal circulation. The rise in placental GH may explain the pregnancy-induced rise in maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase significantly in normally growing fetuses from 18 to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene polymorphisms have been described. IGF-I gene polymorphisms are associated with birth weight in some studies but not in all. Likewise, IGF-I gene polymorphisms are associated with serum IGF-I in healthy adults in some studies, although some controversy exists. Serum IGF-I decreases with increasing age in healthy adults, and this decline could hypothetically be responsible for the increased risk of IHD with ageing. A recent nested case-control study found that adults without IHD, but with low circulating IGF-I levels and high IGF binding protein-3 levels, had a significantly increased risk of developing IHD during a 15-year follow-up period. In summary, the GH/IGF-I axis is involved in the regulation of fetal growth. Furthermore, it has been suggested that low IGF-I may increase the risk of IHD in otherwise healthy subjects. Hypothetically, intrauterine programming of the GH/IGF axis may influence postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease.

Endocrine and metabolic regulation of muscle growth and body composition in cattle

“…In cattle, the IGF-I, IGF-II and insulin receptor concentrations were shown to decrease throughout foetal development from 3 to 5 months of age onwards in both the skeletal muscle (Boge et al, 1995;Listrat et al, 1999b) and the heart (Hocquette et al, 2006 for IGF-I and insulin receptors only). In various mammals, increase in IGF-I (Jensen et al, 2003 for humans) and IGF-II plasma levels (Listrat et al, 1999a for cattle) were observed throughout gestation. Therefore, the IGF-I, IGF-II and insulin receptor levels are the lowest at the end of gestation when the IGF-I levels in foetuses are the highest, when foetal glucose level is the lowest and when foetal GLUT4 expression increases (Hocquette et al, 2006).…”

Amniotic fluid insulin-like growth factor binding protein 3 concentration as early indicator of fetal growth restriction

“…IGF-1 gene was shown to · contain a Variable Number of Tandem Repeats (VNTR) in the promoter region and IGFBP3 gene a single nucleotide polymorphism (SNP) (A_, C) at position -202 in the promoter region. [15][16][17][18][19][20] If some controversy exists on the association between IGF-1 VNTR and JGF-1 s'erum values, most studies showed a significant reduction of IGF-1 concentrations in non-carriers of the most common allele, 19CA [16][17][18][19][20]. IGFBP3 SNP was shown to correlate with adult IGFBP3 serum concentrations, the mutated C allele being associated with decreased circulating concentrations [21,22].…”

Prenatal developmental changes in glucose transporters, intermediary metabolism and hormonal receptors related to the IGF/insulin-glucose axis in the heart and adipose tissue of bovines

“…Assuming a similar trend for the hormonal status in humans and cattle i.e. an increase in IGF-I levels throughout gestation [4] and taking into account the increase in IGF-II plasma levels with increasing age in foetal cattle [53], IGF-I, IGF-II and insulin receptor levels would be low at those stages where IGF-I and placental GH levels in pregnant females and IGF-I levels in foetuses are the highest [4], when foetal glucose level is the lowest and when foetal GLUT4 expression increases (present study). Furthermore, other in vitro studies with cultured cells from the rat hindlimb during differentiation have shown that GLUT1 is abundant in myoblasts, whereas GLUT4 is expressed in spontaneously contracting myotubes but absent in myoblasts [10].…”

“…For the heart, cardiovascular diseases may also be partly programmed during intrauterine growth [1,3]. Furthermore, low birth weight has been associated with an increased incidence of ischemia [4] or cardiovascular diseases [5]. The challenge is, nowadays, to understand the basic biological mechanisms which control tissue differentiation and how they are regulated by nutritional factors.…”

“…The challenge is, nowadays, to understand the basic biological mechanisms which control tissue differentiation and how they are regulated by nutritional factors. It has been suggested that IGF-I may serve as a link between foetal growth and cardiovascular disease [4]. Furthermore, specific studies have been carried out on the insulinglucose axis which is of major importance for the control of body composition and insulin sensitivity and hence for the incidence of diabetes [6,7].…”