Advanced maternal age (AMA) and 75 g oGTT glucose levels are pedictors for insulin therapy in women with gestational diabetes (GDM)

Josefine Theresia Koenigbauer; Laura Fangmann; Paul Rostin; Selina Balke; Petra Weid; Wolfgang Henrich; Alexander Weichert; Göbl Christian

doi:10.1515/jpm-2023-0170

Article

Advanced maternal age (AMA) and 75 g oGTT glucose levels are pedictors for insulin therapy in women with gestational diabetes (GDM)

Josefine Theresia Koenigbauer , Laura Fangmann , Paul Rostin , Selina Balke , Petra Weid , Wolfgang Henrich , Alexander Weichert and Göbl Christian

Published/Copyright: July 20, 2023

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Journal of Perinatal Medicine Volume 51 Issue 9

Abstract

Objectives

Gestational diabetes (GDM) is a common complication during pregnancy that is strongly associated with adverse fetal and maternal outcomes. Advanced maternal age (≥35 years) is a known risk factor for GDM. Studies advocate that GDM comprises distinctive metabolic entities, suggesting an individualized approach based on early pregnancy characteristics (such as 75 g oGTT values, maternal age, obstetric history).

Methods

The oGTT blood glucose levels of 1,664 women were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated postprandial hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values after glucose application. These three subtypes were analysed regarding baseline characteristics as well as fetal and maternal outcome in the context of maternal age.

Results

This analysis reveals that the 75 g oGTT levels and maternal age can distinguish metabolic phenotypes in women with GDM. The overall rate of insulin therapy required was higher in women from the GDM-CH group and increased with maternal age (31.7 %, 38.2 %, <35 years, ≥35–39 years respectively, vs. total insulin rate 22.3 %, p-value <0.001). Women ≥35 years displayed a significantly higher caesarean delivery (CD) rate (<35 years 34.6 %, 38.4 %, 41.1 % vs. ≥35 years 54.8 %, 47.6 %, 46.5 %, GDM-IFH, GDM-IPH, GDM-CH respectively, p-value <0.001).

Conclusions

Women with fasting hyperglycemia, especially those with combined hyperglycemia and advanced maternal age (AMA) display a higher risk for unfavorable perinatal outcome. A categorization based on oGTT values and maternal age, as well as other characteristics can facilitate a basis for clinical risk stratification. Women at risk should receive an individualized and intensified perinatal care as well as interventional therapies.

Keywords: advanced maternal age; GDM; gestational diabetes; insulin; OGTT

Corresponding author: Josefine Theresia Koenigbauer, Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; and Prenatal Diagnosis Bergmannstrasse, Bergmannstrasse 102 Berlin, Germany, E-mail: josefine.koenigbauer@charite.de

Acknowledgments

We thank Petra Weid for initiating this analysis and her wonderful and heartwarming work at the Charité Diabetes Clinic for almost two decades. We are thankful to work with all the motivated mothers and families, willing to make a difference for the future of their children.

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Ethical approval was received from the Ethics Committee of Charité University Hospital on February 6th, 2023 (EA2/255/22).

References

1. Group, HSCR, Metzger, BE, Lowe, LP, Dyer, AR, Trimble, ER, Chaovarindr, U, et al.. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.10.1056/NEJMoa0707943Search in Google Scholar PubMed

2. Metzger, BE, Gabbe, SG, Persson, B, Buchanan, TA, Catalano, PM, Damm, P, et al.. International Association of D, Pregnancy Study Groups Consensus P. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–82. https://doi.org/10.2337/dc09-1848.Search in Google Scholar PubMed PubMed Central

3. Franzago, M, Fraticelli, F, Stuppia, L, Vitacolonna, E. Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child. Epigenetics 2019;14:215–35. https://doi.org/10.1080/15592294.2019.1582277.Search in Google Scholar PubMed PubMed Central

4. Huy, C, Loerbroks, A, Hornemann, A, Rohrig, S, Schneider, S. Prevalence, trend and determining factors of gestational diabetes in Germany. Geburtshilfe Frauenheilkd 2012;72:311–5. https://doi.org/10.1055/s-0031-1298390.Search in Google Scholar PubMed PubMed Central

5. Helseth, SA, Waschbusch, DA, Gnagy, EM, Onyango, AN, Burrows-MacLean, L, Fabiano, GA, et al.. Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-only, ADHD and conduct problems, and controls. J Consult Clin Psychol 2015;83:280–92. https://doi.org/10.1037/a0038505.Search in Google Scholar PubMed PubMed Central

6. Paulo, MS, Abdo, NM, Bettencourt-Silva, R, Al-Rifai, RH. Gestational diabetes mellitus in Europe: a systematic review and meta-analysis of prevalence studies. Front Endocrinol 2021;12:691033. https://doi.org/10.3389/fendo.2021.691033.Search in Google Scholar PubMed PubMed Central

7. Reitzle, L, Schmidt, C, Heidemann, C, Icks, A, Kaltheuner, M, Ziese, T, et al.. Gestational diabetes in Germany: development of screening participation and prevalence. J Health Monit 2021;6:3–18. https://doi.org/10.25646/8325.Search in Google Scholar PubMed PubMed Central

8. (Destatis) SB. Zahl der Woche Nr 18 vom 3. Mai 2022 2022 [05/03/2023]. Available from: https://www.destatis.de/DE/Presse/Pressemitteilungen/Zahl-der-Woche/2022/PD22_18_p002.html#:∼:text=WIESBADEN%20%E2%80%93%20In%20Deutschland%20waren%20im,Mai%20mitteilt Search in Google Scholar

9. Teede, HJ, Harrison, CL, Teh, WT, Paul, E, Allan, CA. Gestational diabetes: development of an early risk prediction tool to facilitate opportunities for prevention. Aust N Z J Obstet Gynaecol 2011;51:499–504. https://doi.org/10.1111/j.1479-828x.2011.01356.x.Search in Google Scholar

10. Kalok, A, Peraba, P, Shah, SA, Mahdy, ZA, Jamil, MA, Kampan, N, et al.. Screening for gestational diabetes in low-risk women: effect of maternal age. Horm Mol Biol Clin Invest 2018;34. https://doi.org/10.1515/hmbci-2017-0071.Search in Google Scholar PubMed

11. Lamminpaa, R, Vehvilainen-Julkunen, K, Gissler, M, Selander, T, Heinonen, S. Pregnancy outcomes in women aged 35 years or older with gestational diabetes – a registry-based study in Finland. J Matern Fetal Neonatal Med 2016;29:55–9. https://doi.org/10.3109/14767058.2014.986450.Search in Google Scholar PubMed

12. Pinheiro, RL, Areia, AL, Mota Pinto, A, Donato, H. Advanced maternal age: adverse outcomes of pregnancy, A meta-analysis. Acta Med Port 2019;32:219–26. https://doi.org/10.20344/amp.11057.Search in Google Scholar PubMed

13. Lean, SC, Derricott, H, Jones, RL, Heazell, AEP. Advanced maternal age and adverse pregnancy outcomes: a systematic review and meta-analysis. PLoS One 2017;12:e0186287. https://doi.org/10.1371/journal.pone.0186287.Search in Google Scholar PubMed PubMed Central

14. Waters, TP, Dyer, AR, Scholtens, DM, Dooley, SL, Herer, E, Lowe, LP, et al.. Maternal and neonatal morbidity for women who would Be added to the diagnosis of GDM using IADPSG criteria: a secondary analysis of the hyperglycemia and adverse pregnancy outcome study. Diabetes Care 2016;39:2204–10. https://doi.org/10.2337/dc16-1194.Search in Google Scholar PubMed PubMed Central

15. Hillier, TA, Pedula, KL, Ogasawara, KK, Vesco, KK, Oshiro, CES, Lubarsky, SL, et al.. A pragmatic, randomized clinical trial of gestational diabetes screening. N Engl J Med 2021;384:895–904. https://doi.org/10.1056/nejmoa2026028.Search in Google Scholar

16. Crowther, CA, Hiller, JE, Moss, JR, McPhee, AJ, Jeffries, WS, Robinson, JS, et al.. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477–86. https://doi.org/10.1056/nejmoa042973.Search in Google Scholar

17. Crowther, CA, Samuel, D, McCowan, LME, Edlin, R, Tran, T, McKinlay, CJ, et al.. Lower versus higher glycemic criteria for diagnosis of gestational diabetes. N Engl J Med 2022;387:587–98. https://doi.org/10.1056/nejmoa2204091.Search in Google Scholar

18. Kuo, CH, Chen, SC, Fang, CT, Nien, FJ, Wu, ET, Lin, SY, et al.. Screening gestational diabetes mellitus: the role of maternal age. PLoS One 2017;12:e0173049. https://doi.org/10.1371/journal.pone.0173049.Search in Google Scholar PubMed PubMed Central

19. Tai, YY, Lee, CN, Kuo, CH, Lin, MW, Chen, KY, Lin, SY, et al.. Simplifying the screening of gestational diabetes by maternal age plus fasting plasma glucose at first prenatal visit: a prospective cohort study. PLoS One 2020;15:e0237224. https://doi.org/10.1371/journal.pone.0237224.Search in Google Scholar PubMed PubMed Central

20. Rayanagoudar, G, Hashi, AA, Zamora, J, Khan, KS, Hitman, GA, Thangaratinam, S. Quantification of the type 2 diabetes risk in women with gestational diabetes: a systematic review and meta-analysis of 95,750 women. Diabetologia 2016;59:1403–11. https://doi.org/10.1007/s00125-016-3927-2.Search in Google Scholar PubMed PubMed Central

21. Schafer-Graf, UM, Gembruch, U, Kainer, F, Groten, T, Hummel, S, Hosli, I, et al.. Gestational diabetes mellitus (GDM) – diagnosis, treatment and follow-up. Guideline of the DDG and DGGG (S3 level, AWMF registry number 057/008, February 2018). Geburtshilfe Frauenheilkd 2018;78:1219–31. https://doi.org/10.1055/a-0659-2596.Search in Google Scholar PubMed PubMed Central

22. Clausen, TD, Mathiesen, ER, Hansen, T, Pedersen, O, Jensen, DM, Lauenborg, J, et al.. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care 2008;31:340–6. https://doi.org/10.2337/dc07-1596.Search in Google Scholar PubMed

23. Gillman, MW, Oakey, H, Baghurst, PA, Volkmer, RE, Robinson, JS, Crowther, CA. Effect of treatment of gestational diabetes mellitus on obesity in the next generation. Diabetes Care 2010;33:964–8. https://doi.org/10.2337/dc09-1810.Search in Google Scholar PubMed PubMed Central

24. Kotzaeridi, G, Blatter, J, Eppel, D, Rosicky, I, Linder, T, Geissler, F, et al.. Characteristics of gestational diabetes subtypes classified by oral glucose tolerance test values. Eur J Clin Invest 2021;51:e13628. https://doi.org/10.1111/eci.13628.Search in Google Scholar PubMed PubMed Central

25. Bogdanet, D, Egan, A, Reddin, C, Kirwan, B, Carmody, L, Dunne, F. Atlantic dip: despite insulin therapy in women with IADPSG diagnosed GDM, desired pregnancy outcomes are still not achieved. What are we missing? Diabetes Res Clin Pract 2018;136:116–23. https://doi.org/10.1016/j.diabres.2017.12.003.Search in Google Scholar PubMed

26. Meregaglia, M, Dainelli, L, Banks, H, Benedetto, C, Detzel, P, Fattore, G. The short-term economic burden of gestational diabetes mellitus in Italy. BMC Pregnancy Childbirth 2018;18:58. https://doi.org/10.1186/s12884-018-1689-1.Search in Google Scholar PubMed PubMed Central

27. Kusinski, LC, Murphy, HR, De Lucia Rolfe, E, Rennie, KL, Oude Griep, LM, Hughes, D, et al.. Dietary intervention in pregnant women with gestational diabetes; protocol for the DiGest randomised controlled trial. Nutrients 2020;12:1165. https://doi.org/10.3390/nu12041165.Search in Google Scholar PubMed PubMed Central

28. Landon, MB, Spong, CY, Thom, E, Carpenter, MW, Ramin, SM, Casey, B, et al.. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339–48. https://doi.org/10.1056/nejmoa0902430.Search in Google Scholar

29. Dong, Y, Wang, L, Lu, Y, Fu, Z, Du, Y, Wang, L. Factors affecting mode of delivery in women of advanced maternal age. Biosci Trends 2021;15:61–3. https://doi.org/10.5582/bst.2020.03375.Search in Google Scholar PubMed

30. Jeong, Y, Choo, SP, Yun, J, Kim, EH. Effect of maternal age on maternal and perinatal outcomes including cesarean delivery following induction of labor in uncomplicated elderly primigravidae. Medicine 2021;100:e27063. https://doi.org/10.1097/md.0000000000027063.Search in Google Scholar

31. Deng, L, Ning, B, Yang, H. Association between gestational diabetes mellitus and adverse obstetric outcomes among women with advanced maternal age: a retrospective cohort study. Medicine 2022;101:e30588. https://doi.org/10.1097/md.0000000000030588.Search in Google Scholar PubMed PubMed Central

32. Jang, HC, Cho, NH, Min, YK, Han, IK, Jung, KB, Metzger, BE. Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM. Diabetes Care 1997;20:1582–8. https://doi.org/10.2337/diacare.20.10.1582.Search in Google Scholar PubMed

33. Zhang, P, Haymar, T, Al-Sayyed, F, Dygulski, S, Dygulska, B, Devi, A, et al.. Placental pathology associated with maternal age and maternal obesity in singleton pregnancy. J Matern Fetal Neonatal Med 2022;35:9517–26. https://doi.org/10.1080/14767058.2022.2044777.Search in Google Scholar PubMed

Received: 2023-04-24

Accepted: 2023-05-20

Published Online: 2023-07-20

Published in Print: 2023-11-27

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/jpm-2023-0170

Keywords for this article

advanced maternal age; GDM; gestational diabetes; insulin; OGTT

Advanced maternal age (AMA) and 75 g oGTT glucose levels are pedictors for insulin therapy in women with gestational diabetes (GDM)

Article

Abstract

Objectives

Methods

Results

Conclusions

Acknowledgments

References

Articles in the same Issue

Articles in the same Issue

Articles in the same Issue

Advanced maternal age (AMA) and 75 g oGTT glucose levels are pedictors for insulin therapy in women with gestational diabetes (GDM)