Insulinlike growth factors (IGFs) exert profound effects on somatic growth and cellular proliferation of many tissues and play an essential role in bone metabolism. The aim of this study was to investigate how fetal growth and bone mineralization correlate with IGF-I and IGF-binding protein-3 (IGFBP-3) levels of newborn infants and their mothers. In addition, we aimed to determine the predictive value of anthropometric measurements on variability in bone mineral status. Umbilical cord venous blood samples were obtained at delivery from 100 term newborn infants. Forty of the newborn infants had birthweights appropriate for gestational age (AGA), 30 were small for gestational age (SGA), and 30 were large for gestational age (LGA). Data were acquired using whole-body dual-energy X-ray absorptiometry scanner with a pediatric platform. Umbilical cord serum IGF-I concentrations were higher in LGA newborns ( P < 0.01), but lower in SGA newborns ( P < 0.01) than in AGA newborns. Umbilical cord serum IGFBP-3 concentrations in LGA newborns were significantly greater than in SGA and AGA newborns ( P < 0.01 and P < 0.01, respectively). Whole-body bone mineral density (WB BMD) was higher in LGA babies (0.442 +/- 0.025 g/cm2 [SD]; P < 0.01) but lower in SGA (0.381 +/- 0.027 g/cm 2; P < 0.0001) than in AGA babies (0.426 +/- 0.022 g/cm2). WB BMD and content (WB BMC) were correlated significantly with birthweight, birth height, head circumference, body mass index (BMI) of the infants; ponderal index and triceps skinfold thickness (reflecting fat stores) of the infants; cord serum IGF-I concentration, serum IGF-I concentration of the mothers; and fat mass, proportionate fat mass, weight, and BMI of the mothers. In contrast, WB BMC was also correlated positively with cord serum IGFBP-3 concentration and gestational age, and WB BMD was positively correlated with serum IGFBP-3 levels of the mothers. Umbilical cord serum IGF-I concentration of the infants was correlated significantly with the concentration of the mothers ( R = 0.232; P = 0.020). Umbilical cord serum IGF-I and IGFBP-3 concentrations were correlated significantly with the fat mass, gestational age, birthweight, birth height, head circumference, and BMI of the infants. Umbilical cord IGF-I concentration was also correlated with ponderal index and triceps skinfold thickness of the infants, maternal weight, BMI, and proportionate fat mass of the infants. Stepwise multiple regression analyses showed no significant relation between bone indices (WB BMD, WB BMC) and the infant's or mother's variations including serum IGF-I and IGFBP-3 concentrations. Birthweight and gestational age are related to bone indices. However, the present study does not provide support for the hypothesis that serum IGF-I and IGFBP-3 levels of infants and their mothers may play a major role in the regulation of bone metabolism in the developing skeleton.
"Low levels of IGF-1 in the postnatal period are associated with high IGF-1-levels in adolescence. Low levels of IGF-1 are reported in SGA newborn infants . Low birth weight is a recognized risk factor for the development of type 2 diabetes and hypertension in adulthood  . "
[Show abstract][Hide abstract] ABSTRACT: Common chronic diseases of Western societies, such as coronary heart disease, diabetes mellitus, cancer, hypertension, obesity, dementia, and allergic diseases are significantly influenced by dietary habits. Cow's milk and dairy products are nutritional staples in most Western societies. Milk and dairy product consumption is recommended by most nutritional societies because of their beneficial effects for calcium uptake and bone mineralization and as a source of valuable protein. However, the adverse long-term effects of milk and milk protein consumption on human health have been neglected. A hypothesis is presented, showing for the first time that milk protein consumption is an essential adverse environmental factor promoting most chronic diseases of Western societies. Milk protein consumption induces postprandial hyperinsulinaemia and shifts the growth hormone/insulin-like growth factor-1 (IGF-1) axis to permanently increased IGF-1 serum levels. Insulin/IGF-1 signalling is involved in the regulation of fetal growth, T-cell maturation in the thymus, linear growth, pathogenesis of acne, atherosclerosis, diabetes mellitus, obesity, cancer and neurodegenerative diseases, thus affecting most chronic diseases of Western societies. Of special concern is the possibility that milk intake during pregnancy adversely affects the early fetal programming of the IGF-1 axis which will influence health risks later in life. An accumulated body of evidence for the adverse effects of cow's milk consumption from fetal life to childhood, adolescence, adulthood and senescence will be provided which strengthens the presented hypothesis.
Medical Hypotheses 03/2009; 72(6):631-9. DOI:10.1016/j.mehy.2009.01.008 · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Poor growth in early life is associated with numerous adverse outcomes later in life. In 123 adolescents 16-18 yr of age, the previous findings of a positive relation between size in early life and later bone mass was confirmed. These associations were mediated by the current height and weight, but it was not confirmed that alterations of the GH-IGF axis cause this.
Numerous studies have found associations between low birth weight and disease later in life, including decreased bone mass.
A longitudinal cohort of 16- to 19-year-old adolescents (n = 123) with data on third trimester fetal growth velocity (FGV) was assessed by serial ultrasound measurements, birth weight (BW), and weight at 1 yr. A follow-up study included DXA scan, anthropometric measurements, and measurements of the growth hormone (GH) -IGF-I axis in a representative subpopulation (n = 30).
BW and weight at 1 yr were positively associated with whole body BMC (p = 0.02 and p < 0.0001, respectively), lumbar spine BMC (p = 0.001 and p = 0.03, respectively), and lumbar spine BMD (p = 0.04). After correction for adolescent height and weight, no association remained significant. There was no relation between IGF-I and IGF binding protein 3 (IGFBP-3) levels in adolescence and size in early life or bone mass. In the subpopulation, GH secretion (median, 2.58 versus 4.05), GH pulse mass (median, 10.7 versus 19.4 mU/liter), and total GH (median, 74.9 versus 108.8 mU/liter/12 h) were decreased in the small for gestational age (SGA) group compared with the appropriate for gestational age (AGA) group; this did not reach statistical significance. Likewise, there were no differences in IGF-I, IGF-II, and IGFBP-1, -2, and -3 levels between the SGA and AGA groups. A statistically significant positive association between FGV and adolescent IGF-II was found (B = 199.9, p = 0.006). Significant negative associations between GH measurement and BMC, as well as BMD, were found (B = -0.008, p = 0.005 and B = -0.008, p = 0.006, respectively).
This study confirms the previous findings of a positive relation between size in early life and later BMC, an association apparently independent of the distal part of the GH/IGF-I axis. However, this association may be mediated mainly by postnatal growth determining size of the skeletal envelope rather than an effect of fetal programming on bone mass per se.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2008; 23(3):439-46. DOI:10.1359/jbmr.071034 · 6.83 Impact Factor
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