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Published in: Reproductive Biology and Endocrinology 1/2015

Open Access 01-12-2015 | Research

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus

Authors: April M. Teague, David A. Fields, Christopher E. Aston, Kevin R. Short, Timothy J. Lyons, Steven D. Chernausek

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

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Abstract

Background

Offspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women.

Methods

We conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n = 79) or type 2 or gestational DM (DM-O; n = 45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates.

Results

DM-O were heavier at birth than Con-O (3.7 ± 0.6 vs. 3.4 ± 0.4 kg, p = 0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 ± 14.9 vs. 9.5 ± 9.9 ng/ml in Con-O, p < 0.0001). Leptin was positively associated with birth weight (p = 0.0007) and SSF (p = 0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p = 0.023; DM-O, p = 0.006). PEDF was positively associated with birth weight in all infants (p = 0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p = 0.009). At 1-month, HMWA was positively associated with body weight (p = 0.004), SSF (p = 0.025) and % body fat (p = 0.004) across the cohort.

Conclusions

Maternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in utero exposure to DM imparts hormonal differences on infants even without aberrant growth.
Literature
1.
go back to reference Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000;49:2208–11.PubMedCrossRef Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000;49:2208–11.PubMedCrossRef
2.
go back to reference Wang P, Smit E, Brouwers MCGJ, Goossens GH, van der Kallen CJH, van Greevenbroek MMJ, et al. Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depot. Eur J Endocrinol. 2008;159:713–8.PubMedCrossRef Wang P, Smit E, Brouwers MCGJ, Goossens GH, van der Kallen CJH, van Greevenbroek MMJ, et al. Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depot. Eur J Endocrinol. 2008;159:713–8.PubMedCrossRef
3.
go back to reference Jenkins A, Zhang SX, Gosmanova A, Aston C, Dashti A, Baker MZ, et al. Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients. Diabetes Res Clin Pract. 2008;82:e5–7.PubMedCentralPubMedCrossRef Jenkins A, Zhang SX, Gosmanova A, Aston C, Dashti A, Baker MZ, et al. Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients. Diabetes Res Clin Pract. 2008;82:e5–7.PubMedCentralPubMedCrossRef
4.
go back to reference Matsuyama K, Ogata N, Matsuoka M, Shima C, Wada M, Jo N, et al. Relationship between pigment epithelium-derived factor (PEDF) and renal function in patients with diabetic retinopathy. Mol Vis. 2008;14:992–6.PubMedCentralPubMed Matsuyama K, Ogata N, Matsuoka M, Shima C, Wada M, Jo N, et al. Relationship between pigment epithelium-derived factor (PEDF) and renal function in patients with diabetic retinopathy. Mol Vis. 2008;14:992–6.PubMedCentralPubMed
5.
go back to reference Jenkins AJ, Zhang SX, Rowley KG, Karschimkus CS, Nelson CL, Chung JS, et al. Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes1. Diabet Med. 2007;24:1345–51.PubMedCrossRef Jenkins AJ, Zhang SX, Rowley KG, Karschimkus CS, Nelson CL, Chung JS, et al. Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes1. Diabet Med. 2007;24:1345–51.PubMedCrossRef
6.
go back to reference Jenkins AJ, Fu D, Azar M, Stoner JA, Kaufman DG, Zhang S, et al. Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients. J Diabetes Complications. 2014;28:353–9.PubMedCentralPubMedCrossRef Jenkins AJ, Fu D, Azar M, Stoner JA, Kaufman DG, Zhang S, et al. Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients. J Diabetes Complications. 2014;28:353–9.PubMedCentralPubMedCrossRef
7.
go back to reference Famulla S, Lamers D, Hartwig S, Passlack W, Horrighs A, Cramer A, et al. Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. Int J Obes. 2011;35:762–72.CrossRef Famulla S, Lamers D, Hartwig S, Passlack W, Horrighs A, Cramer A, et al. Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signaling in muscle and fat cells. Int J Obes. 2011;35:762–72.CrossRef
8.
go back to reference Tombran-Tink J, Mazuruk K, Rodriguez IR, Chung D, Linker T, Englander E, et al. Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. Mol Vis. 1996;2:11.PubMed Tombran-Tink J, Mazuruk K, Rodriguez IR, Chung D, Linker T, Englander E, et al. Organization, evolutionary conservation, expression and unusual Alu density of the human gene for pigment epithelium-derived factor, a unique neurotrophic serpin. Mol Vis. 1996;2:11.PubMed
9.
go back to reference Moreno-Navarrete JM, Touskova V, Sabater M, Mraz M, Drapalova J, Ortega F, et al. Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance. Int J Obes. 2013;37:1230–7.CrossRef Moreno-Navarrete JM, Touskova V, Sabater M, Mraz M, Drapalova J, Ortega F, et al. Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance. Int J Obes. 2013;37:1230–7.CrossRef
10.
go back to reference Plunkett BA, Fitchev P, Doll JA, Gerber SE, Cornwell M, Greenstein EP, et al. Decreased expression of pigment epithelium derived factor (PEDF), an inhibitor of angiogenesis, in placentas of unexplained stillbirths. Reprod Biol. 2008;8:107–20.PubMedCrossRef Plunkett BA, Fitchev P, Doll JA, Gerber SE, Cornwell M, Greenstein EP, et al. Decreased expression of pigment epithelium derived factor (PEDF), an inhibitor of angiogenesis, in placentas of unexplained stillbirths. Reprod Biol. 2008;8:107–20.PubMedCrossRef
11.
go back to reference Low HP, Tiwari A, Janjanam J, Qiu L, Chang C-I, Strohsnitter WC, et al. Screening Preeclamptic Cord Plasma for Proteins Associated with Decreased Breast Cancer Susceptibility. Genomics Proteomics Bioinformatics. 2013;11:335–44.PubMedCentralPubMedCrossRef Low HP, Tiwari A, Janjanam J, Qiu L, Chang C-I, Strohsnitter WC, et al. Screening Preeclamptic Cord Plasma for Proteins Associated with Decreased Breast Cancer Susceptibility. Genomics Proteomics Bioinformatics. 2013;11:335–44.PubMedCentralPubMedCrossRef
13.
go back to reference American Diabetes Association. Gestational diabetes mellitus. Diabetes Care. 2003;26 Suppl 1:S103–5. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care. 2003;26 Suppl 1:S103–5.
14.
go back to reference World Health Organization. ICD-10: International statistical classification of diseases and related health problems, 10th revision. 2nd ed. Geneva: World Health Organization; 2004. World Health Organization. ICD-10: International statistical classification of diseases and related health problems, 10th revision. 2nd ed. Geneva: World Health Organization; 2004.
15.
go back to reference Pirc L, Owens J, Crowther C, Willson K, De Blasio M, Robinson J. Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born to mothers in the ACHOIS randomised controlled trial. BMC Pediatr. 2007;7:18.PubMedCentralPubMedCrossRef Pirc L, Owens J, Crowther C, Willson K, De Blasio M, Robinson J. Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born to mothers in the ACHOIS randomised controlled trial. BMC Pediatr. 2007;7:18.PubMedCentralPubMedCrossRef
16.
go back to reference Lea RG, Howe D, Hannah LT, Bonneau O, Hunter L, Hoggard N. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod. 2000;6:763–9.PubMedCrossRef Lea RG, Howe D, Hannah LT, Bonneau O, Hunter L, Hoggard N. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod. 2000;6:763–9.PubMedCrossRef
17.
go back to reference Okereke NC, Uvena-Celebrezze J, Hutson-Presley L, Amini SB, Catalano PM. The effect of gender and gestational diabetes mellitus on cord leptin concentration. Am J Obstet Gynecol. 2002;187:798–803.PubMedCrossRef Okereke NC, Uvena-Celebrezze J, Hutson-Presley L, Amini SB, Catalano PM. The effect of gender and gestational diabetes mellitus on cord leptin concentration. Am J Obstet Gynecol. 2002;187:798–803.PubMedCrossRef
18.
go back to reference Persson B, Westgren M, Celsi G, Nord E, Ortqvist E. Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers. Horm Metab Res. 1999;31:467–71.PubMedCrossRef Persson B, Westgren M, Celsi G, Nord E, Ortqvist E. Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers. Horm Metab Res. 1999;31:467–71.PubMedCrossRef
19.
go back to reference Gross GA, Solenberger T, Philpott T, William L, Holcomb J, Landt M. Plasma leptin concentrations in newborns of diabetic and nondiabetic mothers. Am J Perinatol. 1998;15:243–7.PubMedCrossRef Gross GA, Solenberger T, Philpott T, William L, Holcomb J, Landt M. Plasma leptin concentrations in newborns of diabetic and nondiabetic mothers. Am J Perinatol. 1998;15:243–7.PubMedCrossRef
20.
go back to reference Higgins MF, Russell NM, Brazil DP, Firth RG, McAuliffe FM. Fetal and maternal leptin in pre-gestational diabetic pregnancy. Int J Gynaecol Obstet. 2013;120:169–72.PubMedCrossRef Higgins MF, Russell NM, Brazil DP, Firth RG, McAuliffe FM. Fetal and maternal leptin in pre-gestational diabetic pregnancy. Int J Gynaecol Obstet. 2013;120:169–72.PubMedCrossRef
21.
go back to reference Manderson JG, Patterson CC, Hadden DR, Traub AI, Leslie H, McCance DR. Leptin concentrations in maternal serum and cord blood in diabetic and nondiabetic pregnancy. Am J Obstet Gynecol. 2003;188:1326–32.PubMedCrossRef Manderson JG, Patterson CC, Hadden DR, Traub AI, Leslie H, McCance DR. Leptin concentrations in maternal serum and cord blood in diabetic and nondiabetic pregnancy. Am J Obstet Gynecol. 2003;188:1326–32.PubMedCrossRef
22.
go back to reference The HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med. 2008;358:1991–2002.CrossRef The HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med. 2008;358:1991–2002.CrossRef
23.
go back to reference Hibino S, Itabashi K, Nakano Y, Inoue M, Tanaka D, Maruyama T. Longitudinal Changes in High Molecular Weight Serum Adiponectin Levels in Healthy Infants. Pediatr Res. 2009;65:363–6.PubMedCrossRef Hibino S, Itabashi K, Nakano Y, Inoue M, Tanaka D, Maruyama T. Longitudinal Changes in High Molecular Weight Serum Adiponectin Levels in Healthy Infants. Pediatr Res. 2009;65:363–6.PubMedCrossRef
24.
go back to reference Ballesteros M, Simón I, Vendrell J, Ceperuelo-Mallafré V, Miralles RM, Albaiges G, et al. Maternal and Cord Blood Adiponectin Multimeric Forms in Gestational Diabetes Mellitus: A prospective analysis. Diabetes Care. 2011;34:2418–23.PubMedCentralPubMedCrossRef Ballesteros M, Simón I, Vendrell J, Ceperuelo-Mallafré V, Miralles RM, Albaiges G, et al. Maternal and Cord Blood Adiponectin Multimeric Forms in Gestational Diabetes Mellitus: A prospective analysis. Diabetes Care. 2011;34:2418–23.PubMedCentralPubMedCrossRef
25.
go back to reference Luo Z-C, Nuyt A-M, Delvin E, Fraser WD, Julien P, Audibert F, et al. Maternal and fetal leptin, adiponectin levels and associations with fetal insulin sensitivity. Obesity. 2013;21:210–6.PubMedCrossRef Luo Z-C, Nuyt A-M, Delvin E, Fraser WD, Julien P, Audibert F, et al. Maternal and fetal leptin, adiponectin levels and associations with fetal insulin sensitivity. Obesity. 2013;21:210–6.PubMedCrossRef
26.
go back to reference Cortelazzi D, Corbetta S, Ronzoni S, Pelle F, Marconi A, Cozzi V, et al. Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies. Clin Endocrinol (Oxf). 2007;66:447–53.PubMedCrossRef Cortelazzi D, Corbetta S, Ronzoni S, Pelle F, Marconi A, Cozzi V, et al. Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies. Clin Endocrinol (Oxf). 2007;66:447–53.PubMedCrossRef
27.
go back to reference Siahanidou T, Margeli A, Garatzioti M, Davradou M, Apostolakou F, Papassotiriou I, et al. Disparity in circulating adiponectin multimers between term and preterm infants. J Perinat Med. 2009;37:683–8.PubMedCrossRef Siahanidou T, Margeli A, Garatzioti M, Davradou M, Apostolakou F, Papassotiriou I, et al. Disparity in circulating adiponectin multimers between term and preterm infants. J Perinat Med. 2009;37:683–8.PubMedCrossRef
28.
go back to reference Mantzoros CS, Rifas-Shiman SL, Williams CJ, Fargnoli JL, Kelesidis T, Gillman MW. Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study. Pediatrics. 2009;123:682–9.PubMedCentralPubMedCrossRef Mantzoros CS, Rifas-Shiman SL, Williams CJ, Fargnoli JL, Kelesidis T, Gillman MW. Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study. Pediatrics. 2009;123:682–9.PubMedCentralPubMedCrossRef
29.
go back to reference Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, et al. Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin. Diabetes. 1998;47:847–50.PubMedCrossRef Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, et al. Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin. Diabetes. 1998;47:847–50.PubMedCrossRef
30.
go back to reference Yamagishi S-i, Amano S, Inagaki Y, Okamoto T, Takeuchi M, Inoue H. Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc Res. 2003;65:186–90.PubMedCrossRef Yamagishi S-i, Amano S, Inagaki Y, Okamoto T, Takeuchi M, Inoue H. Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc Res. 2003;65:186–90.PubMedCrossRef
31.
go back to reference Böhm A, Ordelheide A-M, Machann J, Heni M, Ketterer C, Machicao F, et al. Common Genetic Variation in the SERPINF1 Locus Determines Overall Adiposity, Obesity-Related Insulin Resistance, and Circulating Leptin Levels. PLoS ONE. 2012;7:e34035.PubMedCentralPubMedCrossRef Böhm A, Ordelheide A-M, Machann J, Heni M, Ketterer C, Machicao F, et al. Common Genetic Variation in the SERPINF1 Locus Determines Overall Adiposity, Obesity-Related Insulin Resistance, and Circulating Leptin Levels. PLoS ONE. 2012;7:e34035.PubMedCentralPubMedCrossRef
32.
go back to reference Langer O, Conway DL, Berkus MD, Xenakis EM-J, Gonzales O. A Comparison of Glyburide and Insulin in Women with Gestational Diabetes Mellitus. N Engl J Med. 2000;343:1134–8.PubMedCrossRef Langer O, Conway DL, Berkus MD, Xenakis EM-J, Gonzales O. A Comparison of Glyburide and Insulin in Women with Gestational Diabetes Mellitus. N Engl J Med. 2000;343:1134–8.PubMedCrossRef
33.
go back to reference Lain KY, Garabedian MJ, Daftary A, Jeyabalan A. Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared with insulin. Am J Obstet Gynecol. 2009;200:501. e1-.e6.PubMedCrossRef Lain KY, Garabedian MJ, Daftary A, Jeyabalan A. Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared with insulin. Am J Obstet Gynecol. 2009;200:501. e1-.e6.PubMedCrossRef
Metadata
Title
Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus
Authors
April M. Teague
David A. Fields
Christopher E. Aston
Kevin R. Short
Timothy J. Lyons
Steven D. Chernausek
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-015-0061-9

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