Gestational diabetes mellitus in the last trimester – a feature of maternal iron excess?
Abstract
SUMMARY Aim To determine whether non‐anaemic women with gestational diabetes mellitus (GDM) diagnosed in third trimester pregnancy have evidence of increased iron stores compared with matched non‐diabetic controls. Methods In a prospective study, women who had antenatal booking before 20 weeks' gestation and without anaemia or diabetes mellitus were recruited at the time of the oral glucose tolerance test (OGTT) at 28–31 weeks' gestation for the study of serum ferritin, iron and transferrin concentrations. The results were blinded to the managing obstetricians. After delivery, the records were reviewed. The cases diagnosed as GDM were compared with a control group (two controls for each index case matched for parity) selected at random from the at‐risk but nondiabetic cases. Results GDM was diagnosed in 97 of the 401 women recruited. Compared with the 194 controls, there was no difference in the weight, body mass index, booking and third trimester haemoglobin, or third trimester red cell indices, but concentrations of serum ferritin, iron, transferrin saturation, and the post‐natal haemoglobin were significantly higher. On multiple regression analysis, maternal BMI and the log‐transformed ferritin concentration remained significant determinants of the OGTT 2‐h glucose value. Conclusion The results suggest an association between increased iron stores and glucose intolerance at the third trimester in non‐anaemic women. The role of iron excess in the pathogenesis of GDM needs to be examined.
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Iron excess is a known feature of gestational diabetes and a clear risk factor for diabetes even in normal populations; diabetes is a classical consequence of iron overloading in hereditary haemochromatosis.
“Iron 'excess' is also a known feature of gestational diabetes [591-593], and is a clear risk factor for the disease even in 'normal' populations [594-603], and indeed diabetes is a classical consequence of iron overloading as seen in hereditary haemochromatosis [604].”
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“[12,13] [14-16] There is evidence of a link between insulin metabolism and excess body iron, since in frequent blood donors who have iron deficiency postprandial hyperinsulinemia is reduced, leading to enhanced insulin sensitivity and diabetes prevention.”
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“In addition, epidemiological studies have reported an association between high Fe stores as a pro-oxidant and increased risk of cardiovascular disease (50), metabolic syndrome (51), gestational diabetes (52, 53), and type 2 diabetes (54-56).”
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BackgroundPrepregnancy hemoglobin levels and gestational diabetes mellitus in pregnancy
Kim, H., Kim, J., Noh, E., Ahn, K. H., Cho, G. J., Hong, S., Oh, M., & Kim, H.-J. (2020) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2020.108608 · Cited by 37 · see citing works
Iron metabolism in diabetes-induced Alzheimer’s disease: a focus on insulin resistance in the brain
Chung, J. Y., Kim, H.-S., & Song, J. (2018) · BioMetals · doi:10.1007/s10534-018-0134-2 · Cited by 37 · see citing works
Devrím, E., Tarhan, İ., Ergüder, B. İ., & Durak, İ. (2006) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2006.07.004 · Cited by 35 · see citing works
Schreinemachers, D. M., & Ghio, A. J. (2016) · Environmental Health Insights · doi:10.4137/ehi.s36225 · Cited by 32 · see citing works
Soheilykhah, S., Mojibian, M., & Moghadam, M. J. (2017) · International Journal of Reproductive BioMedicine (IJRM) · doi:10.29252/ijrm.15.3.155 · Cited by 32 · see citing works
“Some data have demonstrated that iron excess may have a role in insulin resistance at the cellular level (16, 10).”
BackgroundKinnunen, T. I., Luoto, R. M., Helin, A., & Hemminki, E. (2014) · Maternal and Child Nutrition · doi:10.1111/mcn.12139 · Cited by 32 · see citing works
Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy
Fisher, A. L., Sangkhae, V., Balušíková, K., Palaskas, N. J., Ganz, T., & Nemeth, E. (2021) · Nature Communications · doi:10.1038/s41467-021-24333-z · Cited by 32 · see citing works
Zhang, H.-Y., Teng, X., Shan, Z., Wang, Z., Li, C., Yu, X., Mao, J., Wang, W., Xie, X., & Teng, W. (2019) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000409 · Cited by 30 · see citing works
Ferritin and iron supplements in gestational diabetes mellitus: less or more?
Li, T., Zhang, J., & Li, P. (2023) · European Journal of Nutrition · doi:10.1007/s00394-023-03250-5 · Cited by 31 · see citing works
Iron homeostasis and insulin sensitivity: unraveling the complex interactions
Sobieska, K., Buczyńska, A., Kretowski, A. J., & Popławska‐Kita, A. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-024-09908-7 · Cited by 34 · see citing works
“The findings indicate that there is a probable association between increased iron stores and glucose intolerance at the third trimester in non-anaemic women [24].”
BackgroundAjayi, O. B., Oyetayo, F. L., & Akomolafe, S. F. (2020) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-020-03053-9 · Cited by 29 · see citing works
“Excess cytosolic iron is a common factor of gestational diabetes [52] and a vivid risk factor for the disease in normal populations [53].”
BackgroundRehema, A. (2004) · DSpace repository (University of Tartu) · Cited by 29 · see citing works
Are iron supplements appropriate for iron replete pregnant women?
Weinberg, E. D. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.04.039 · Cited by 28 · see citing works
Sharifi, F., Ziaee, V., Feizy, Mousavinasab, S. N. A. D., Anjomshoaa, & Mokhtari, M. (2010) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmsott.s15049 · Cited by 39 · see citing works
“There is an increasing recognition that iron overload may play a role in insulin resistance at the cellular level.(10,11) Some epidemiologic studies have reported higher levels of ferritin in women with GDM.”
Correlation Between High Serum Ferritin Level and Gestational Diabetes: A Systematic Review
Durrani, L., Ejaz, S., Tavares, L. B., Mohyeldin, M., Abu-Reesh, D., Boorenie, M., & Khan, S. (2021) · Cureus · doi:10.7759/cureus.18990 · Cited by 30 · see citing works
“Moreover, elevated levels of hemoglobin in early pregnancy have been identified as an independent GDM risk factor [18-19].”
BackgroundZhao, Y., Gao, Q., Li, B.-J., Wang, Y., & Wang, Y. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1177547 · Cited by 26 · see citing works
Preconceptional Iron Intake and Gestational Diabetes Mellitus
Darling, A. M., Mitchell, A. A., & Werler, M. M. (2016) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13060525 · Cited by 24 · see citing works
Kaygusuz, İ., Gümüş, İ. İ., Yılmaz, S., Simavlı, S. A., Uysal, S., Derbent, A. U., Gözdemir, E., & Kafalı, H. C. (2013) · Gynecologic and Obstetric Investigation · doi:10.1159/000348560 · Cited by 25 · see citing works
Anémie par carence martiale et grossesse. Prévention et traitement
Beucher, G., Grossetti, E., Simonet, T., Leporrier, M., & Dreyfus, M. (2011) · Journal de gynécologie, obstétrique et biologie de la reproduction. Supplément/Journal de gynécologie obstétrique et biologie de la reproduction · doi:10.1016/j.jgyn.2011.01.004 · Cited by 23 · see citing works
Yu, F.-J., Huang, M., Chang, W., Chung, H., Wu, C.-Y., Shin, S., & Hsu, C. (2012) · Annals of Nutrition and Metabolism · doi:10.1159/000339265 · Cited by 20 · see citing works
Impact of iron supplementation on gestational diabetes mellitus: A literature review
Liu, L., Yan, F., Yan, H., & Wang, Z. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14886 · Cited by 19 · see citing works
Miranda, V. I. A., Pizzol, T. D. S. D., de Jesus, P. R., Silveira, M. P. T., & Bertoldi, A. D. (2022) · Revista Brasileira Ginecologia e Obstetrícia · doi:10.1055/s-0042-1755460 · Cited by 19 · see citing works
Oboh, G., Olabiyi, A. A., & Akinyemi, A. J. (2013) · Pharmaceutical Biology · doi:10.3109/13880209.2013.782321 · Cited by 17 · see citing works
“Excess cytosolic iron is a known factor of gestational diabetes (Lao et al., 2001) and a clear risk factor for the disease in normal populations (Fernández-Real et al.”
BackgroundIron, Human Growth, and the Global Epidemic of Obesity
Sangani, R. G., & Ghio, A. J. (2013) · Nutrients · doi:10.3390/nu5104231 · Cited by 15 · see citing works
Insights into the pathogenesis of gestational and hepatic diseases: the impact of ferroptosis
You, Y., Qian, Z., Jiang, Y., Chen, L., Wu, D., Liu, L., Zhang, F., Ning, X., Zhang, Y., & Xiao, J. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1482838 · Cited by 16 · see citing works
Bal, M., Ersoy, G. Ş., Demirtaş, Ö., Kurt, S., & Taşyurt, A. (2016) · Journal of Turkish Society of Obstetric and Gynecology · doi:10.4274/tjod.10170 · Cited by 15 · see citing works
“Similarly, it has been reported that increased serum iron levels might be related to GDM risk in pregnant women(14,15).”
BackgroundSeven-Year Surveillance of the Clinical Performance of a Blood Glucose Test Strip Product
Setford, S. J., Grady, M., Phillips, S., Miller, L., Mackintosh, S., Cameron, H., & Corrigall, K. (2017) · Journal of Diabetes Science and Technology · doi:10.1177/1932296817703133 · Cited by 15 · see citing works
“Another report has shown that Hct of pregnant women averaged 35%, equivalent to a similar group of women with gestational diabetes.(18) Providing consistent accuracy across the glucose range at these lower Hct levels is therefore important throughout pregnancy.”
ResultWu, Y., Zhang, Q., & Xiao, X. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.763809 · Cited by 13 · see citing works
“Pregnant women with increased Fe stores are at higher risk of developing gestational diabetes mellitus (90).”
BackgroundSerum Elemental Analysis of Type 2 Diabetes Patients Using SRXRF
Rao, N. S., Raju, G. J. N., Tiwari, M. K., Naidu, B. G., & Sarita, P. (2021) · Biological Trace Element Research · doi:10.1007/s12011-021-02762-7 · Cited by 12 · see citing works
Anémie par carence martiale et grossesse. Prévention et traitement
Beucher, G., Grossetti, E., Simonet, T., Leporrier, M., & Dreyfus, M. (2011) · Sages-Femmes · doi:10.1016/j.sagf.2011.07.005 · Cited by 12 · see citing works
Iron regulatory protein 2 deficiency may correlate with insulin resistance
Zhou, Y., Wu, W., Xu, Z., Liu, Y., Chang, H., Yu, P., Zhang, X., Yu, Y., Liu, K., & Chang, Y. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.01.022 · Cited by 12 · see citing works
Does high maternal first trimester iron status have an effect on the 50 g oral glucose test?
Yeniel, A. Ö., Ergenoğlu, A. M., Sanhal, C. Y., Şahin, Ç., Ulukuş, M., & Öztekin, K. (2012) · Journal of Obstetrics and Gynaecology · doi:10.3109/01443615.2012.658894 · Cited by 10 · see citing works
“In another study, which was done by the same investigators, it was also reported that mean ferritin levels were higher among women with GDM compared to those without GDM (Lao et al. 2001).”
ResultHIGH SERUM FERRITIN CONCENTRATIONS IN POLYCYSTIC OVARY SYNDROME IS NOT RELATED TO INSULIN RESISTANCE
Sharifi, F., Mazloomi, S., & Mousavinasab, N. (2011) · Iranian journal of diabetes and obesity · Cited by 10 · see citing works
Current literature in diabetes
Nazlıel, B., Yetkin, İ., İrkeç, C., & Koçer, B. (2001) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.173 · Cited by 10 · see citing works
Lin, Y., Wu, C., An, R., Liu, H., Chen, M., Tan, H., Chen, L., & Deng, J. (2022) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.15509 · Cited by 9 · see citing works
Akinbami, A., Gbadegesin, A., John‐Olabode, S., Adediran, A., Dosunmu, A. O., Sobande, A. A., & Uche, E. I. (2015) · HIV/AIDS - Research and Palliative Care · doi:10.2147/hiv.s80137 · Cited by 9 · see citing works
Zhang, Z., Li, X., Zhou, X., Zhang, Y., Gan, X.-P., Xu, X., & Wu, H. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1067655 · Cited by 9 · see citing works
“Furthermore, our findings are also in accordance with results from previously published prospective studies in non-pregnant individuals on iron store and type 2 diabetes (16) (17) (18).”
ResultPrasad, D. K. V. (2013) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000269 · Cited by 9 · see citing works
“Women with body mass index >26 kg/m2 has shown that who developed World Health Organization category of impaired glucose tolerance, with the 2-hr glucose values of the 75 g OGTT between 144 mg to 196 mg/dL (WHO, 1980) during pregnancy has significantly increased hemoglobin concentration compared with body mass index m…”
BackgroundIron Biomarker in Gestational Diabetes Pathogenesis
xiao, P. X. (2014) · Journal of Molecular Biomarkers & Diagnosis · doi:10.4172/2155-9929.1000205 · Cited by 9 · see citing works
“Unadjusted concentrations of serum ferritin, iron, transferrin saturation, and the post-natal hemoglobin were significantly higher at 28–31 wk gestation in cases with GDM compared with controls [35].”
BackgroundNovel Iron Parameters in Patients with Type 2 Diabetes Mellitus in Relation to Kidney Function
Zapora-Kurel, A., Kuźma, Ł., Zakrzewska, M., Żórawski, M., Dobrzycki, S., Twardowska-Kawalec, M., & Małyszko, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10163732 · Cited by 8 · see citing works
Epidemiology of gestational diabetes mellitus
Yogev, Y., Haroush, A. B., Hod, M., & Oats, J. J. N. (2018) · CRC Press eBooks · doi:10.1201/9781315382104-8 · Cited by 8 · see citing works
Maternal micronutrient disturbance as risks of offspring metabolic syndrome
Shi, Y., Zhong, H., & Pang, L. (2023) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2022.127097 · Cited by 10 · see citing works
The Role of Ferroptosis in Women's Health and Diseases
Xu, Q., Zhu, C., Lin, L., Li, J., An, Z., & Tang, C. K. (2025) · MedComm · doi:10.1002/mco2.70296 · Cited by 7 · see citing works
Role of Maternal Iron Status in the Pathogenesis Of Gestational Diabetes Mellitus
Sarker, M. R., Jebunnesa, F., Khatun, T., Helal, R., Ali, L., & Rahim, A. T. M. (2014) · Bangladesh Medical Journal · doi:10.3329/bmj.v40i3.18678 · Cited by 7 · see citing works
Yong, H. Y., Shariff, Z. M., Yusof, B. N. M., Rejali, Z., Tee, Y. Y. S., Bindels, J., & van der Beek, E. M. (2022) · British Journal Of Nutrition · doi:10.1017/s000711452100502x · Cited by 7 · see citing works
“Previous retrospective and prospective studies found that high maternal Hb (more than 13 g/dl) in the first trimester(8), and at 28–30thweeks of gestation(9) are independent risk factors for GDM.”
ResultEbinç, H., Ebinç, F. A., & Özkurt, Z. N. (2007) · Saudi Medical Journal · doi:10.15537/1658-3175.3837 · Cited by 5 · see citing works
HFE Gene Mutation Associated with the Severity of Gestational Diabetes Mellitus in Belarusian Women
Sivitskaya, L. N., Даниленко, Н. Г., Zabarouskaya, Z., & Davydenko, O. G. (2013) · Open Journal of Endocrine and Metabolic Diseases · doi:10.4236/ojemd.2013.31002 · Cited by 4 · see citing works
“Free radicals synthesized in reactions with iron injure cells [23,24].”
BackgroundAigner, E. S., & Datz, C. (2008) · Cited by 4 · see citing works
Misra, S., Yew, Y. W., & Shin, T. S. (2019) · AIMS Medical Science · doi:10.3934/medsci.2019.1.76 · Cited by 3 · see citing works
“Hong Kong Lao, Chan, & Tam, 2001 Prospective cohort study [32] Fe Association of non-anaemic GDM diagnosed in third trimester and their Fe stores compared with matched non-GDM controls.”
- Authors
- Lao, T. T., Chan, P. L., & Tam, K. F.
- Affiliations
- Tsan Yuk Hospital (CN)
- Corresponding author
- Lao, T. T.
- Venue
- Diabetic Medicine
- Publisher
- Wiley
- Published
- 2001-03
- Volume
- 18
- Issue
- 3
- Pages
- 218-223
- ISSN
- 0742-3071 (ISSN-L)
- 1464-5491
- OpenAlex
- W1988582933
- Cited by
- 137
- References
- 35
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 11 · 2015: 5 · 2014: 11 · 2013: 9 · 2012: 7
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetic Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- gestational diabetes mellitus, iron overload, iron stores, serum ferritin, transferrin saturation, third trimester, impaired glucose tolerance, body mass index
- MeSH terms
- Adult, Birth Weight, Cross-Sectional Studies, Female, Ferritins, Gestational Age, Glucose Tolerance Test, Hemoglobins, Humans, Infant, Newborn, Iron, Maternal Age, Pregnancy, Pregnancy Trimester, Third, Reference Values, Transferrin, Diabetes, Gestational, Dietary Supplements
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