Skip to main content

Advertisement

SpringerLink
Log in

Bone Mass Accrual in First Six Months of Life: Impact of Maternal Diabetes, Infant Adiposity, and Cord Blood Adipokines

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

The perinatal period is a time of substantial bone mass accrual with many factors affecting long-term bone mineralization. Currently it is unclear what effect maternal gestational/type 2 diabetes has on infant bone mass accrual. This is a prospective study of offspring of Native American and Hispanic mothers with normoglycemia (n = 94) and gestational diabetes or type 2 diabetes (n = 64). Infant anthropometrics were measured at birth, 1, and 6 months of age. Cord blood leptin, high-molecular weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF), vascular epithelium growth factor (VEGF), endoglin, and C-peptide were measured by ELISA. Infants had bone mineral density measurement at 1 month or/and 6 months of age using dual-energy x-ray absorptiometry scan. Mothers with diabetes were older (31 ± 6 years vs 25 ± 4 years) and had higher pre-pregnancy BMI (32.6 ± 5.8 vs 27.2 ± 6.4 kg/m2) than control mothers. Mean HbA1C of mothers with diabetes was 5.9 ± 1.0% compared to 5.1 ± 0.3% in controls early in pregnancy. Infants born to mothers with diabetes (DM-O) were born at a slightly lower gestational age compared to infants born to control mothers (Con-O). There was no difference in total body less head bone mineral content (BMC) or bone mineral density (BMD) between DM-O and Con-O. For both groups together, bone area, BMD, and BMC tracked over the first 6 months of life (r: 0.56, 0.38, and 0.48, respectively). Percent fat was strongly and positively correlated with BMC at 1 month of age (r = 0.44; p < 0.001) and BMC at both 1 and 6 months of age correlated strongly with birth weight. There were no associations between infant bone mass and cord blood leptin, PEDF, or VEGF, while C-peptide had a significant correlation with BMC at 1 and 6 months only in DM-O (p = 0.01 and 0.03, respectively). Infants born to mothers with well-controlled gestational/type 2 diabetes have normal bone mass accrual. Bone mineral content during this time is highly correlated with indices of infant growth and the association of bone mineral indices with percent body fat suggests that bone-fat crosstalk is operative early in life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ryan S (1998) Bone mineralization in preterm infants. Nutrition 14(10):745–747

    Article  CAS  Google Scholar 

  2. Dennison EM, Cooper C, Cole ZA (2010) Early development and osteoporosis and bone health. J Dev Orig Health Dis 1(3):142–149

    Article  CAS  Google Scholar 

  3. Harvey N, Dennison E, Cooper C (2014) Osteoporosis: a lifecourse approach. J Bone Miner Res 29(9):1917–1925

    Article  Google Scholar 

  4. Yang Y, Wu F, Dwyer T, Antony B, Winzenberg T, Jones G (2020) Associations of breastfeeding, maternal smoking, and birth weight with bone density and microarchitecture in young adulthood: a 25-year birth-cohort study. J Bone Miner Res 35(9):1652–1659

    Article  Google Scholar 

  5. Sudhagoni RG, Wey HE, Djira GD, Specker BL (2012) Longitudinal effects of fat and lean mass on bone accrual in infants. Bone 50(3):638–642

    Article  Google Scholar 

  6. Seeman E (1994) Reduced bone density in women with fractures: contribution of low peak bone density and rapid bone loss. Osteoporos Int 4(Suppl 1):15–25

    Article  Google Scholar 

  7. Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg J, Mathiesen ER, Clausen TD (2016) Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia 59(7):1396–1399

    Article  CAS  Google Scholar 

  8. Chen J, Yang X, Huang L, Zhang Z, Yao J, Liang H et al (2021) Insulin resistance biomarkers in small-for-gestational-age infants born to mothers with gestational diabetes mellitus. J Mater-Fetal & Neonatal Med. https://doi.org/10.1080/14767058.2021.2014449

    Article  Google Scholar 

  9. Gou BH, Guan HM, Bi YX, Ding BJ (2019) Gestational diabetes: weight gain during pregnancy and its relationship to pregnancy outcomes. Chin Med J (Engl) 132(2):154–160

    Article  CAS  Google Scholar 

  10. Minton SD, Steichen JJ, Tsang RC (1983) Decreased bone mineral content in small-for-gestational-age infants compared with appropriate-for-gestational-age infants: normal serum 25-hydroxyvitamin D and decreasing parathyroid hormone. Pediatrics 71(3):383–388

    Article  CAS  Google Scholar 

  11. Mughal MZ, Ross R, Tsang RC (1989) Clearance of calcium across in situ perfused placentas of intrauterine growth-retarded rat fetuses. Pediatr Res 25(4):420–422

    Article  CAS  Google Scholar 

  12. Namgung R, Tsang RC (2000) Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization. Proceedings of the Nutrition Society 59(1):55–63

    Article  CAS  Google Scholar 

  13. Littner Y, Mandel D, Mimouni FB, Dollberg S (2004) Decreased bone ultrasound velocity in large-for-gestational-age infants. J Perinatol 24(1):21–23

    Article  Google Scholar 

  14. Mimouni F, Steichen JJ, Tsang RC, Hertzberg V, Miodovnik M (1988) Decreased bone mineral content in infants of diabetic mothers. Am J Perinatol 5(4):339–343

    Article  CAS  Google Scholar 

  15. Lapillonne A, Guerin S, Braillon P, Claris O, Delmas PD, Salle BL (1997) Diabetes during pregnancy does not alter whole body bone mineral content in infants. J Clin Endocrinol Metab 82(12):3993–3997

    Article  CAS  Google Scholar 

  16. Schushan-Eisen I, Cohen M, Leibovitch L, Maayan-Metzger A, Strauss T (2015) Bone density among infants of gestational diabetic mothers and macrosomic neonates. Matern Child Health J 19(3):578–582

    Article  Google Scholar 

  17. Regev RH, Dolfin T, Eliakim A, Arnon S, Bauer S, Nemet D et al (2004) Bone speed of sound in infants of mothers with gestational diabetes mellitus. J Pediatr Endocrinol Metab 17(8):1083–1088

    Article  Google Scholar 

  18. Guarnotta V, Mineo MI, Giacchetto E, Imbergamo MP, Giordano C (2021) Maternal-foetal complications in pregnancy: a retrospective comparison between type 1 and type 2 diabetes mellitus. BMC Pregnancy Childbirth 21(1):243

    Article  Google Scholar 

  19. Belinsky GS, Sreekumar B, Andrejecsk JW, Saltzman WM, Gong J, Herzog RI et al (2016) Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. FASEB J 30(8):2837–2848

    Article  CAS  Google Scholar 

  20. Upadhyay J, Farr OM, Mantzoros CS (2015) The role of leptin in regulating bone metabolism. Metabolism 64(1):105–113

    Article  CAS  Google Scholar 

  21. Malekzadeh B, Erlandsson MC, Tengvall P, Palmquist A, Ransjo M, Bokarewa MI et al (2018) Effects of implant-delivered insulin on bone formation in osteoporotic rats. J Biomed Mater Res A 106(9):2472–2480

    Article  CAS  Google Scholar 

  22. Hu K, Olsen BR (2016) The roles of vascular endothelial growth factor in bone repair and regeneration. Bone 91:30–38

    Article  CAS  Google Scholar 

  23. Teague AM, Fields DA, Aston CE, Short KR, Lyons TJ, Chernausek SD (2015) Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus. Reprod Biol Endocrinol 13:68

    Article  Google Scholar 

  24. ACOG Practice Bulletin No (2018) 190: gestational diabetes mellitus. Obstet Gynecol 131(2):49–64

    Article  Google Scholar 

  25. Venkataraman PS, Ahluwalia BW (1992) Total bone mineral content and body composition by x-ray densitometry in newborns. Pediatrics 90(5):767–770

    Article  CAS  Google Scholar 

  26. Yarbrough DE, Barrett-Connor E, Morton DJ (2000) Birth weight as a predictor of adult bone mass in postmenopausal women: the Rancho Bernardo Study. Osteoporos Int 11(7):626–630

    Article  CAS  Google Scholar 

  27. Martinez-Mesa J, Menezes AM, Howe LD, Wehrmeister FC, Muniz LC, Gonzalez-Chica DA et al (2014) Lifecourse relationship between maternal smoking during pregnancy, birth weight, contemporaneous anthropometric measurements and bone mass at 18years old. The 1993 Pelotas Birth Cohort. Early Human Devel 90(12):901–906

    Article  Google Scholar 

  28. Kirk B, Feehan J, Lombardi G, Duque G (2020) Muscle, bone, and fat crosstalk: the biological role of myokines, osteokines, and adipokines. Curr Osteoporos Rep 18(4):388–400

    Article  Google Scholar 

  29. Wang Y, Zhang X, Shao J, Liu H, Liu X, Luo E (2017) Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway. Sci Rep 7(1):3652

    Article  Google Scholar 

  30. Kanazawa I (2017) Interaction between bone and glucose metabolism [Review]. Endocr J 64(11):1043–1053

    Article  CAS  Google Scholar 

  31. Reid IR, Baldock PA, Cornish J (2018) Effects of Leptin on the Skeleton. Endocr Rev 39(6):938–959

    Article  Google Scholar 

  32. Cock TA, Auwerx J (2003) Leptin: cutting the fat off the bone. Lancet 362(9395):1572–1574

    Article  CAS  Google Scholar 

  33. Javaid MK, Godfrey KM, Taylor P, Robinson SM, Crozier SR, Dennison EM et al (2005) Umbilical cord leptin predicts neonatal bone mass. Calcif Tissue Int 76(5):341–347

    Article  CAS  Google Scholar 

  34. Akcakus M, Kurtoglu S, Koklu E, Kula M, Koklu S (2007) The relationship between birth weight leptin and bone mineral status in newborn infants. Neonatology 91(2):101–106

    Article  CAS  Google Scholar 

  35. Schubring C, Siebler T, Kratzsch J, Englaro P, Blum WF, Triep K et al (1999) Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight. Clin Endocrinol (Oxf) 51(2):199–204

    Article  CAS  Google Scholar 

  36. Fulzele K, Clemens TL (2012) Novel functions for insulin in bone. Bone 50(2):452–456

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank study coordinators Mary Ayn Tullier, Justin Fowler, Olufolake Olufowote, and Shelly Hopper; the Choctaw Nation of Oklahoma, and the Chickasaw Nation and our study participants and families. This study was supported by NIH Grants R01 DK089034-03 (S. Chernausek, PI) and P20 MD000528-05 (T.Lyons, project PI); American Diabetes Association and Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award (IDeA) from NIGMS (C. Aston). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Harold Hamm Diabetes Center, 1200, Children’s avenue Suite 4500, Oklahoma City, OK, 73104, USA

    Sowmya Krishnan, Christopher E. Aston, David A. Fields & Steven D. Chernausek

  2. Harold Hamm Diabetes Center, Oklahoma City, OK, USA

    April M. Teague

  3. Division of Endocrinology, Diabetes and Metabolic Diseases at the Medical University of South Carolina, Charleston, SC, USA

    Timothy J. Lyons

  4. Diabetes Free South Carolina, BlueCross BlueShield of South Carolina, Columbia, SC, USA

    Timothy J. Lyons

Authors
  1. Sowmya Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher E. Aston
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David A. Fields
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. April M. Teague
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Timothy J. Lyons
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steven D. Chernausek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sowmya Krishnan.

Ethics declarations

Conflict of interest

The authors Sowmya Krishnan, Christopher E. Aston, David A. Fields, April M. Teague, Timothy J. Lyons and Steven D. Chernausek have no conflicts of interest to declare.

Ethical Approval

Signed informed consent was obtained from a parent of each infant in accordance with the University of Oklahoma Health Sciences Center, Chickasaw Nation and/or Choctaw Nation of Oklahoma institutional review boards, each of which approved the study. All clinical investigations have been conducted according to the principles expressed in the Declaration of Helsinki.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krishnan, S., Aston, C.E., Fields, D.A. et al. Bone Mass Accrual in First Six Months of Life: Impact of Maternal Diabetes, Infant Adiposity, and Cord Blood Adipokines. Calcif Tissue Int 111, 248–255 (2022). https://doi.org/10.1007/s00223-022-00990-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-022-00990-0

Keywords

Search

Navigation