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Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants

  • N. Nagano (a1), T. Okada (a1), R. Fukamachi (a1), K. Yoshikawa (a1), S. Munakata (a1), Y. Usukura (a1), S. Hosono (a1), S. Takahashi (a1), H. Mugishima (a1), M. Matsuura (a2) and T. Yamamoto (a2)...

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = −0.484, P = 0.002) and log VLDL-TG (r = −0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

Corresponding author
*Address for correspondence: T. Okada MD, Department of Pediatrics and Child Health, Nihon University School of Medicine30-1 Oyaguchi Kamicho, Itabashi-ku, Tokyo 173-8610, Japan. (Email
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1.Wollmann HA. Growth hormone and growth factors during perinatal life. Horm Res. 2000; 53(Suppl 1), 5054.
2.Suwa S, Katsumata N, Maesaka H, et al. Serum insulin-like growth factor I (somatomedin-C) level in normal subjects from infancy to adulthood, pituitary dwarfs and normal variant short children. Endocrinol. 1988; 35, 857864.
3.Woods KA, Camacho-Hubner C, Savage MO, et al. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med. 1996; 335, 13631367.
4.Camacho-Hübner C, Woods KA, Miraki-Moud F, et al. Insulin-like growth factor-I deficiency caused by a partial deletion of the IGF-I gene: effects of rhIGF-I therapy. Growth Horm IGF Res. 1999; 9(Suppl B), 4752.
5.Takahashi Y. Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver. Endocr J. 2012; 59, 955962.
6.Conti E, Musumeci MB, De Giusti M, et al. IGF-1 and atherothrombosis: relevance to pathophysiology and therapy. Clin Sci. 2011; 120, 377402.
7.Ungvari Z, Csiszar A. The emerging role of IGF-1 deficiency in cardiovascular aging: recent advances. J Gerontol A Biol Sci Med Sci. 2012; 67, 599610.
8.Colao A, Spiezia S, Di Somma C, et al. Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age. J Endocrinol Invest. 2005; 28, 440448.
9.Succurro E, Arturi F, Grembiale A, et al. Positive association between plasma IGF1 and high-density lipoprotein cholesterol levels in adult nondiabetic subjects. Eur J Endocrinol. 2010; 163, 7580.
10.Zenobi PD, Holzmann P, Glatz Y, et al. Improvement of lipid profile in type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I. Diabetologia. 1993; 36, 465469.
11.Nelson SM, Freeman DJ, Sattar N, et al. IGF-1 and leptin associate with fetal HDL cholesterol at birth: examination in offspring of mothers with type 1 diabetes. Diabetes. 2007; 56, 27052709.
12.Guilloteau P, Zabielski R, Hammon HM, et al. Adverse effects of nutritional programming during prenatal and early postnatal life, some aspects of regulation and potential prevention and treatments. J Physiol Pharmacol. 2009; 60(Suppl 3), 1735.
13.Hanley B, Dijane J, Fewtrell M, et al. Metabolic imprinting, programming and epigenetics – a review of present priorities and future opportunities. Br J Nutr. 2010; 104(Suppl 1), S1S25.
14.Tosh DN, Fu Q, Callaway CW, et al. Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA expression and histone structure in rapid vs. delayed postnatal catch-up growth. Am J Physiol Gastrointest Liver Physiol. 2010; 299, G1023G1029.
15.Fu Q, Yu X, Callaway CW, et al. Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene. FASEB J. 2009; 23, 24382449.
16.Itabashi K, Fujimura M, Kusuda S, et al. Committee on Neonatal Medicine in Japan Pediatric Society. New neonatal anthropometric charts. J Jpn Pediatr Soc. 2010; 114, 12711293 (in Japanese).
17.Okazaki M, Usui S, Ishigami M, et al. Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profile in high-performance liquid chromatography. Arterioscler Thromb Vasc Biol. 2005; 25, 578584.
18.Sakurabayashi I, Saito Y, Kita T, et al. Reference intervals for serum apolipoproteins A-I, A-II, B, C-II, C-III and E in healthy Japanese determined with a commercial immunoturbidimetric assay and effects of sex, age, smoking, drinking, and Lp(a) level. Clin Chim Acta. 2001; 12, 8795.
19.Bansal N, Cruickshank JK, McElduff P, et al. Cord blood lipoproteins and prenatal influences. Curr Opin Lipidol. 2005; 16, 400408.
20.Nagano N, Okada T, Yonezawa R, et al. Early postnatal changes of lipoprotein subclass profile in late preterm infants. Clin Chim Acta. 2012; 413, 109112.
21.Kelishadi R, Badiee Z, Adeli K. Cord blood lipid profile and associated factors: baseline data of a birth cohort study. Paediatr Perinat Epidemiol. 2007; 21, 518524.
22.Cai HJ, Xie CL, Chen Q, et al. The relationship between hepatic low-density lipoprotein receptor activity and serum cholesterol level in the human fetus. Hepatology. 1991; 13, 852857.
23.Diaz M, Leal C, Ramon Y, et al. Cord blood lipoprotein-cholesterol: relationship birth weight and gestational age of newborns. Metabolism. 1989; 38, 435438.
24.Lok F, Owens JA, Mundy L, et al. Insulin-like growth factor I promotes growth selectively in fetal sheep in late gestation. Am J Physiol. 1996; 270(Pt 2), R1148R1155.
25.Fowden AL. The insulin-like growth factors and feto-placental growth. Placenta. 2003; 24, 803812.
26.Ross JT, McMillen IC, Lok F, et al. Intrafetal insulin-like growth factor-I infusion stimulates adrenal growth but not steroidogenesis in the sheep fetus during late gestation. Endocrinology. 2007; 148, 54245432.
27.Parker CR Jr, Carr BR, Simpson ER, et al. Decline in the concentration of low-density lipoprotein-cholesterol in human fetal plasma near term. Metabolism. 1983; 32, 919923.
28.Kaser S, Ebenbichler CF, Wolf HJ, et al. Lipoprotein profile and cholesteryl ester transfer protein in neonates. Metabolism. 2001; 50, 723728.
29.Loukidi-Bouchenak B, Lamri-Senhadji MY, Merzouk S, et al. Serum lecithin: cholesterol acyltransferase activity, HDL2 and HDL3 composition in hypertensive mothers and their small for gestational age newborns. Eur J Pediatr. 2008; 167, 525532.
30.Yoshikawa K, Okada T, Munakata S, et al. Association between serum lipoprotein lipase mass concentration and subcutaneous fat accumulation during neonatal period. Eur J Clin Nutr. 2010; 64, 447453.
31.Kajantie E, Barker DJ, Osmond C, et al. Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort study. Int J Epidemiol. 2008; 37, 280289.
32.Jensen RB, Chellakooty M, Vielwerth S, et al. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life: does insulin-like growth factor-I play a role? Horm Res. 2003; 60(Suppl 3), 136148.
33.IJzerman RG, Stehouwer CD, Van Weissenbruch MM, et al. Evidence for genetic factors explaining the association between birth weight and low-density lipoprotein cholesterol and possible intrauterine factors influencing the association between birth weight and high-density lipoprotein cholesterol: analysis in twins. J Clin Endocrinol Metab. 2001; 86, 54795484.
34.Colangelo LA, Liu K, Gapstur SM, CARDIA Male Hormone Study. Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and cardiovascular disease risk factors in young black men and white men: the CARDIA Male Hormone Study. Am J Epidemiol. 2004; 160, 750757.
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