Association of mid-pregnancy ferritin levels with postpartum glucose metabolism in women with gestational diabetes

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Association of mid-pregnancy ferritin levels with postpartum glucose metabolism in women with gestational diabetes"


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ABSTRACT BACKGROUND Ferritin, a key indicator of body iron levels, has been reported to associate with type 2 diabetes (T2DM) and the onset of Gestational diabetes mellitus (GDM). However,


limited research explores the association between mid-pregnancy ferritin levels and the risk of postpartum abnormal glucose metabolism (AGM) in patients with GDM. METHODS A retrospective


cohort study was conducted in 1514 women with GDM recruited from January 2016 to January 2021, and 916 women were included. Demographic characteristics, medical history and family history,


pregnancy complications were recorded. Multiple logistic regression models were performed to assess the association between mid-pregnancy ferritin levels and the risk of postpartum AGM.


RESULTS Following the postpartum oral glucose tolerance test, 307 (33.5%) exhibited AGM. The AGM group had higher mid-pregnancy serum ferritin levels [AGM vs NGT: 23 (11.7, 69) µg/L vs 17.80


(9.85, 40.7) µg/L, P < 0.001] and had a larger proportion of women with ferritin levels ≥30 µg/L (AGM vs NGT: 43.6% vs 31.4%, P < 0.001). Logistic regression analysis demonstrated


that women with ferritin levels≥ 30 µg/L had a 1.566 times higher risk of developing postpartum AGM. CONCLUSIONS These findings indicate that elevated mid-pregnancy ferritin levels are


significantly and independently associated with increased postpartum AGM risk in women with previous GDM. Consequently, cautious consideration is necessary for prescribing iron supplements


in prenatal care, particularly for non-anemic women with GDM at high risk of developing diabetes after delivery. SIMILAR CONTENT BEING VIEWED BY OTHERS A PROSPECTIVE COHORT STUDY OF


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RETROSPECTIVE STUDY Article Open access 21 March 2024 INTRODUCTION Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance first recognized during pregnancy [1],


affects 4–18% of pregnant women in different countries [2]. GDM increases the risk of maternal and neonatal complications which include caesarean section, preeclampsia, macrosomia,


prematurity, stillbirth, hypoglycemia, congenital malformations, respiratory disorders, etc. [3]. Furthermore, women with GDM have an almost 10-fold higher risk of developing type 2 diabetes


(T2DM) later in life comparted to those without GDM, and the risk is particularly notable in the first five years after delivery [4]. Therefore, the American Diabetes Association (ADA)


recommends a 75-g oral glucose tolerance test (OGTT) to identify abnormal glucose metabolism (AGM) at 4–12 weeks postpartum and lifelong follow-up [5]. Iron is a crucial micronutrient that


plays a critical role in maintaining body homeostasis and is an important factor in the development of hyperglycemia [6,7,8]. Iron deficiency is widespread. The World Health Organization


(WHO) reports that anemia affects 37% of pregnant women worldwide, resulting in increased maternal and fetal complications [9]. Therefore, most countries recommend iron supplementation for


pregnant women [10, 11]. However, excess iron has been implicated in the development of diabetes by affecting oxidative stress damage in the body [12,13,14,15]. Ferritin is the major iron


storage protein and is widely used to reflect iron stores in the body, which can help identify iron overload [6]. It has been reported that high levels of serum ferritin are associated with


T2DM and the development of GDM in pregnant women [7, 8, 16]. Furthermore, recent genetic evidence suggests a causal relationship between elevated systemic iron levels and an increased risk


of T2DM [17]. However, there is a lack of studies that have investigated the association between serum ferritin levels during pregnancy and the subsequent risk of postpartum AGM in patients


with GDM. Therefore, the aim of this study is to investigate the relationship between mid-pregnancy serum ferritin levels and postpartum glucose metabolism in a cohort of 916 Chinese women


with previous GDM. METHODS STUDY POPULATION This retrospective cohort study was conducted at the Department of Endocrinology and Metabolism of Shanghai General Hospital from January 2016 to


January 2021. A total of 1514 women diagnosed with GDM at 24–28 weeks of gestation were recruited for our study. Subjects with chronic diseases including hypertension, diabetes, anemia,


lupus, epilepsy, acute or chronic liver disease, acute or chronic renal disease, heart disease, acute or chronic inflammatory or infective diseases, drug or alcohol abuse, and history of


cancer were excluded. Inclusion criteria were: 1) age≥18 years old; 2) live-birth singleton pregnancy. Of the 1514 participants, 524 women without serum ferritin at gestation of 24–28 weeks


and 74 women without the results of 75-g OGTT at 4–12 weeks postpartum were excluded. Thus, 916 participants were included in the final analysis (Fig. 1). The study was conducted according


to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Shanghai General Hospital. All the participants signed written informed consent. PROCEDURES AND


MEASUREMENTS Demographic characteristics, medical history and family history including age at present pregnancy, pre-pregnancy body mass index (BMI), weight gain during pregnancy,


gestational age, menstrual cycle, parity, history of miscarriage, family history of diabetes and hypertension, were recorded. BMI was calculated as the weight in kilograms divided by the


square of the height in meters (kg/m2). At 24–28 weeks of gestation, a 75-g OGTT was performed and the GDM diagnosis was made if one or more of the following levels were observed according


to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria [18]: fasting plasma glucose (FPG) level ≥5.1 mmol/L, 1-h postprandial glucose (1h-PG) level ≥10.0 


mmol/L and 2-h postprandial glucose (2h-PG) level ≥8.5 mmol/L. Serum ferritin, hemoglobin, serum albumin, bilirubin, serum creatinine, serum uric acid, hemoglobin A1c (HbA1c), glycated


albumin (GA) and other clinical indexes of glucose and lipid metabolism were evaluated at 24–28 weeks of gestation. All blood samples were obtained in the morning after an overnight fast of


8–10 h. Ferritin was measured using automated immunoassay systems (Siemens ADVIA Centaur XPT, Germany). Hemoglobin was measured by auto hematology analyzer (Mindray BC-6800, China). HbA1c


was measured with an autoanalyzer (Lifotronic H8, Japan). The plasma insulin levels were measured using an automated chemiluminescence systems (Abbott i2000, United States). Serum glucose


and lipid profiles including serum total cholesterol (TCH), triglycerides (TG), and serum albumin, bilirubin, serum uric acid, serum creatinine, were measured with an automatic biochemistry


analyzer (Siemens ADVIA2400, Germany). All the testing of samples was performed in the same laboratory. Anemia was diagnosed as hemoglobin concentration <110 g/L for pregnant women


according to the World Health Organization criteria. The homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) was used to estimate the insulin resistance which was defined as


[fasting insulin (lU/ml) * fasting glucose (mmol/l)]/22.5. HOMA of β-cell (HOMA-β), calculated as [20*fasting insulin (lU/ml)] / [fasting glucose (mmol/l) – 3.5], was used to assess β-cell


function [19]. Insulin sensitivity index (ISI) was evaluated by using the Cederholm formula [20]: ISI = M/ [MGLU × lg (MINS)]. M = 75 000/120 + [FPG (mmol/L) − 2h- PG (mmol/L)] × 1.15×180 ×


0.19 × body weight (kg)/120, MGLU = [FPG (mmol/L) + 2h-PG (mmol/L)] /2, lg(MINS) = {lg[fasting insulin (lU/ml)] + lg[2 h insulin (lU/ml)]}/2. Insulin resistance was defined as HOMA-IR ≥ 2.8


[21]. All the participants’ pregnancy complications including premature labor, macrosomia and neonatal hypoglycemia were recorded. Premature labor was defined as labor occurring between


after 20 and before 37 gestational weeks. Macrosomia was defined as birth weight≥4000 g. Neonatal hypoglycemia was defined as blood glucose <2.6 mmol/L. After delivery, an additional 75-g


OGTT was performed 4–12 weeks postpartum. The results were interpreted based on the WHO criteria [22]: 1) normal glucose tolerance (NGT) was defined as FPG < 6.1 mmol/L and 2h-PG < 


7.8 mmol/L; 2) impaired fasting glucose (IFG) was defined as 6.1 ≤ FPG <7.0 mmol/L and 2h-PG <7.8 mmol/L; 3) impaired glucose tolerance (IGT) was defined as FPG <6.1 mmol/L and 7.8 


≤ 2h-PG <11.1 mmol/L; 4) IFG + IGT was defined as 6.1 ≤ FPG <7.0 mmol/L and 7.8 ≤ 2h-PG <11.1 mmol/L; 5) diabetes mellitus (DM) was defined as a FPG ≥ 7.0 mmol/L and/ or 2h-PG ≥ 


11.1 mmol/L; 6) abnormal glucose metabolism (AGM) was defined as IFG and/ or IGT and/ or DM. STATISTICAL ANALYSIS Data were presented as the mean ± standard deviation (SD) or median


(interquartile range, 25–75%) for continuous variables and proportion for categorical variables, respectively. Normally distributed continuous variables between two groups were compared by


Student’s t test, while nonnormally distributed continuous variables between two groups were analyzed by the Mann-Whitney U test. One-way analysis of variance (ANOVA) was used to compare


continuous variables across multiple groups. Post hoc multiple comparisons were conducted using the least significant difference (LSD) method. Categorical variables were analyzed by χ2 test.


Multiple logistic regression models were performed to assess the association between mid-pregnancy ferritin levels and the risk of postpartum AGM by estimating odds ratio (OR) and 95%


confidence intervals (CI) after adjusting for potential confounders. Analyses for association were performed using mid-pregnancy ferritin levels as categorical and continuous variables,


respectively. The association between mid-pregnancy ferritin levels and risk of postpartum AGM was also checked graphically using restricted cubic splines with the ferritin reference level


defined as 30 µg/L. To assess the consistency of the association between mid-pregnancy ferritin levels and the risk of postpartum AGM, subgroup analyses were performed in patients according


to age (<35 or ≥35 years), and pre-pregnancy BMI ( < 24 or ≥24 kg/m2). The spearman correlation coefficients were used to assess the correlation between mid-pregnancy ferritin and


glucose related indicators, insulin secretion and sensitivity indicators. The restricted cubic splines analysis and the corresponding figures were performed with R version 4.1 (R Foundation


for Statistical Computing, Vienna, Austria) using the rms package for restricted cubic splines. The other statistical analyses were performed using SPSS version 26 (IBM Corp., Armonk, NY),


and a P value < 0.05 was considered statistically significant. RESULTS BASELINE CHARACTERISTICS OF THE STUDY POPULATION AND COMPARISON OF BASELINE INDICATORS BETWEEN THE POSTPARTUM NGT


AND AGM GROUPS A total of 916 participants were finally included in this study. According to the postpartum 75-g OGTT results, 609 (66.5%) women returned to NGT. Of the remaining women with


AGM, 7 (0.8%) were diagnosed with IFG, 246 (26.9%) were IGT, 17 (1.9%) were IFG + IGT, and 37 (4.0%) were diabetes. Postpartum HbA1c was significantly higher in DM group than in the other


groups, and postpartum FPG was significantly higher in IFG, IFG + IGT and DM groups than that in NGT and IGT groups (Table 1 and Supplementary Table 1). The comparison of demographics,


clinical characteristics, and pregnancy complications between the NGT and AGM groups was illustrated in Table 1. Among the 916 participants, 307 (33.5%) were AGM, 25.4% were aged 35 years or


older, and 26.2% had a pre-pregnancy BMI of 24 kg/m2 or higher. All participants underwent a lifestyle intervention, and 17.8% of the subjects received insulin therapy during pregnancy.


Subjects in the AGM group were older and had higher pre-pregnancy BMI. Furthermore, the AGM group exhibited significantly elevated levels of mid-pregnancy FPG, 1h-PG, 2h-PG, HbA1c, GA,


HOMA-IR, TG, as well as elevated HOMA-IR in both mid-pregnancy and postpartum. Conversely, the AGM group exhibited reduced mid-pregnancy and postpartum ISI. Additionally, the AGM group had a


higher proportion of participants aged≥35 years, pre-pregnancy BMI ≥ 24 kg/m2, those received insulin therapy, and HOMA-IR ≥ 2.8 in mid-pregnancy and postpartum. Notably, the AGM group also


showed significantly higher mid-pregnancy serum ferritin levels [AGM vs NGT: 23 (11.7, 69) µg/L vs 17.80 (9.85, 40.7) µg/L, P < 0.001] and a greater proportion of participants with


ferritin levels ≥30 µg/L (AGM vs NGT: 43.6% vs 31.4%, P < 0.001). However, there were no significant differences in other clinical characteristics between the two groups, including


gestational age, hemoglobin levels, HOMA-β, TCH, albumin, total bilirubin, uric acid, creatinine, the proportion of individuals with a family history of hypertension and diabetes, history of


miscarriage, as well as pregnancy complications (Table 1). ASSOCIATION OF MID-PREGNANCY SERUM FERRITIN AND THE RISK OF POSTPARTUM AGM To determine the association between serum ferritin


levels and the risk of postpartum AGM, logistic regression analysis was performed. The results revealed that the women with ferritin levels≥ 30 µg/L had a 1.678 times higher likelihood of


developing postpartum AGM than those with ferritin levels <30 µg/L after adjusting for age and pre-pregnancy BMI (OR = 1.678, 95% CI: 1.259–2.236, P < 0.001) (Table 2). This


association remained after further adjusting for weight gain during pregnancy, mid-pregnancy hemoglobin, FPG and HbA1c (OR = 1.566, 95% CI: 1.162–2.111, P = 0.003) (Table 2). Consistently,


the risk of postpartum AGM also increased linearly with increasing mid-pregnancy ferritin levels as a continuous variable (Fig. 2), and every 1 µg/L increase in ferritin was associated with


a 0.5% increase in the developing of postpartum AGM after adjusting for potential confounding factors (OR = 1.005, 95% CI: 1.001–1.008, P = 0.012) (Table 2). SUBGROUP ANALYSIS Advanced


maternal age is markedly linked with adverse obstetrical and perinatal outcomes, which is usually defined as maternal age above 35 years. According to the Working Group on Obesity in China,


overweight was defined as a 24 ≤ BMI < 28 kg/m2 and obesity was defined as BMI ≥ 28 kg/m2. Subgroup analysis was conducted to further explore the association between serum ferritin levels


and the risk of postpartum AGM in these different population groups. The results indicated that the association between serum ferritin levels and the risk of postpartum AGM was consistent


across subgroups stratified by age (<35 or ≥35 years) and pre-pregnancy BMI ( < 24 or ≥24 kg/m2) (Fig. 3). ASSOCIATIONS OF MID-PREGNANCY FERRITIN WITH GLYCEMIC AND INSULIN SECRETION


AND SENSITIVITY PARAMETERS The Spearman correlation analysis showed that mid-pregnancy ferritin was positively correlated with mid-pregnancy and postpartum HbA1c, GA, HOMA-β (P < 0.001),


negatively correlated with mid-pregnancy and postpartum ISI (r = −0.115, P = 0.001 and r = −0.125, P < 0.001 respectively) (Table 3). DISCUSSION In this retrospective cohort study, we


aimed to investigated the relationship between mid-pregnancy serum ferritin levels and the subsequent risk of postpartum AGM in a cohort of 916 Chinese women with previous GDM. Our findings


revealed that women in the postpartum AGM group had higher levels of mid-pregnancy serum ferritin and a greater proportion of women with ferritin levels ≥30 µg/L. Furthermore, our studies


showed that elevated mid-pregnancy ferritin levels were independently associated with an increased risk of postpartum AGM. Most previous studies have reported a significant association


between elevated serum ferritin levels during pregnancy and the risk of GDM. In a prospective observational study conducted by Cheng et al., involving 851 Chinese pregnant women, it was


observed that elevated serum ferritin levels in early pregnancy were significantly associated with an increased risk of GDM [23]. Similarly, Pandey et al. also conducted a prospective


observational study and reported that serum ferritin levels in early second trimester of pregnancy were associated with the development of GDM [24]. They suggested that serum ferritin level


could be used as a predictive marker for the development of GDM. Furthermore, a systematic review has indicated that high maternal serum ferritin levels play a significant role in the


development of GDM [8]. Wang et al. provided evidence that systemic iron status could be a causal factor in T2DM development using an mendelian randomization approach [17]. However, there is


limited research on the association between serum ferritin levels during pregnancy or postpartum and postpartum hyperglycemia. Sharifi et al. conducted a study on 64 women with GDM and


found no significant association between mid-pregnancy ferritin levels and OGTT results at 8 weeks postpartum [25]. Hershenfeld S et al. also conducted a study on 105 women with previous GDM


and 235 women without GDM and found no significant difference in serum ferritin levels between the two groups at 1 or 3 years postpartum. Moreover, neither baseline ferritin at 1 year


postpartum nor its change over the subsequent 2 years was associated with glucose tolerance at 3 years [26]. In a 6-year postpartum follow-up study conducted by Källner et al., involving 157


women with GDM, no significant differences in ferritin levels were found between the postpartum NGT and impaired glucose metabolism (IGM) groups [27]. Therefore, it emerges that neither


serum ferritin during pregnancy nor postpartum is associated with postpartum glucose metabolism in women with previous GDM. In contrast to previous studies, our study, which involved 916


women diagnosed with GDM, revealed that the AGM group exhibited markedly elevated mid-pregnancy serum ferritin levels. A serum ferritin concentration less than 30 µg/L was mostly used for


identification of iron deficiency [28]. In our study, we showed that ferritin levels≥ 30 µg/L were significantly associated with an increased risk of developing postpartum AGM after


adjustment for multiple covariates. The association between serum ferritin levels and the risk of postpartum AGM was consistent across different subgroups. The disparity between our findings


and those of previous studies might due to variations in follow-up duration or the sample size. Previous studies had sample sizes of less than 200, whereas ours involved nearly 1000


participants. Therefore, it is essential to conduct multicenter studies with larger cohorts and longer follow-up periods to validate our findings. Recent researches suggested that iron may


play a role in the pathophysiology of diabetes and GDM. Ferritin, the main iron storage protein, can serve as an indicator of the body’s iron reserves. However, the exact mechanism


underlying the elevation of serum ferritin in the development of abnormal glucose metabolism remains unclear. Many studies suggest that an excess of iron can initiate oxidative stress damage


to pancreatic β-cells and induce insulin resistance by catalyzing the production of reactive oxygen species (ROS), thereby increasing the risk of diabetes. Mice with targeted deletion of


Hfe, a model for hemochromatosis, exhibit elevated iron content in islets, increased oxidative stress in β-cells, and a decrease in insulin secretion capacity [29]. Furthermore, iron


overload can also induce oxidative stress damage to the liver. The liver plays a crucial role in glucose metabolism. In an experiment on stressed rats, iron supplementation exacerbated iron


deposition and oxidative stress damage in the liver, leading to the development of persistent hyperglycemia [30]. Additionally, ferritin is also regarded as an acute-phase inflammatory


reactant, and elevated ferritin levels promote the inflammatory process. This, in turn, leads to increased insulin resistance, reduced pancreatic insulin secretion, and liver dysfunction


[31]. In our study, we observed a negative correlation between mid-pregnancy ferritin and postpartum ISI, as well as a positive correlation with postpartum HOMA-β. However, we did not


identify a significant correlation between mid-pregnancy ferritin and postpartum HOMA-IR. This lack of correlation may be attributed to the fact that the HOMA-IR used in this study


specifically assessed fasting insulin resistance, whereas the ISI calculated through the Cederholm formula reflects insulin sensitivity after glucose load. We speculated that oxidative


stress damage induced by high ferritin levels during mid-pregnancy may have long-lasting effects, persisting into the postpartum period and contributing to impaired insulin sensitivity. In


this scenario, pancreatic β-cells may struggle to compensate for the insulin resistance adequately, resulting in glucose metabolism disorders. Therefore, further mechanistic studies are


imperative for a comprehensive understanding. Iron is a crucial micronutrient, and iron deficiency anemia (IDA) during pregnancy is associated with an increased risk of maternal and fetal


complications. Therefore, most countries recommend iron supplementation in pregnant women to prevent IDA. However, available evidence suggests that high iron intake during pregnancy


increases the risk of GDM [32,33,34,35,36]. Based on our study and previous studies, routine iron supplementation should be reconsidered in pregnant women with normal serum ferritin levels


due to the associated risks of GDM and postpartum AGM. The reported incidence of postpartum AGM ranged from 2.6% to 38% within 12 weeks postpartum [37, 38]. In our study, 33.5% of women


exhibited abnormal glucose tolerance, with 0.8% had IFG, 26.9% had IGT, 1.9% had both IFG and IGT, and 4% had diabetes. Despite recommendations for women with GDM to undergo a glucose


tolerance test at 4–12 weeks postpartum, screening rate remain low [39, 40]. This underscores the necessity for intensified efforts to incentivize more women with GDM to undergo screening


for T2DM. A systematic review revealed that factors such as pre-pregnancy BMI, family history of diabetes, non-white ethnicity, advanced maternal age, elevated FPG, HbA1c levels and insulin


use during pregnancy were significantly associated with the increased risk of developing T2DM in women with previous GDM [41, 42]. Furthermore, our study identified that in the postpartum


AGM group also exhibited characteristics such as advanced maternal age, higher pre-pregnancy BMI, elevated FPG, postprandial blood glucose (PBG), and HbA1c levels, as well as a higher


frequency of insulin usage. Our study has several limitations. Firstly, ferritin is considered as an acute-phase inflammatory reactant and is influenced by inflammation. We did not evaluate


inflammatory factors such as C Reactive Protein (CRP), which could potentially impact our findings. Secondly, we didn’t collect information on iron supplement use, so further research on the


relationship between iron supplement and postpartum GDM is needed. Thirdly, we did not assess postpartum ferritin levels or evaluate the ferritin trajectory from mid-pregnancy to the


postpartum period and their association with postpartum glucose metabolism. Lastly, our follow-up period was relatively short, warranting consideration for longer-term assessments. In


conclusion, our study showed that high levels of ferritin during mid-pregnancy are significantly and independently associated with an increased risk of postpartum AGM in women with previous


GDM, suggesting that mid-pregnancy ferritin could serve as an indicator of early postpartum AGM risk. Iron supplements as part of prenatal care, especially for women with GDM who do not have


anemia, should be approached cautiously, especially for those at high risk of developing DM after delivery. DATA AVAILABILITY The datasets generated during and analyzed during the current


study are available from the corresponding author on reasonable request. REFERENCES * Buchanan TA, Xiang A, Kjos SL, Watanabe R. What is gestational diabetes? Diab Care. 2007;30:S105–111.


Article  CAS  Google Scholar  * Cundy T, Ackermann E, Ryan EA. Gestational diabetes: new criteria may triple the prevalence but effect on outcomes is unclear. Bmj. 2014;348:g1567–g1567.


Article  PubMed  Google Scholar  * Johns EC, Denison FC, Norman JE, Reynolds RM. Gestational diabetes mellitus: mechanisms, treatment, and complications. Trends Endocrinol Metab.


2018;29:743–54. Article  CAS  PubMed  Google Scholar  * Vounzoulaki E, Khunti K, Abner SC, Tan BK, Davies MJ, Gillies CL. Progression to type 2 diabetes in women with a known history of


gestational diabetes: systematic review and meta-analysis. Bmj. 2020;369:m1361. Article  PubMed  PubMed Central  Google Scholar  * American Diabetes Association Professional Practice


Committee. 2. Classification and diagnosis of diabetes:standards of medical care in diabetes—2022. _Diabetes Care_. 2022;45:S17–S38. * Abbaspour N, Hurrell R, Kelishadi R. Review on iron and


its importance for human health. J Res Med Sci. 2014;19:164–74. PubMed  PubMed Central  Google Scholar  * Liu J, Li Q, Yang Y, Ma L. Iron metabolism and type 2 diabetes mellitus: A


meta-analysis and systematic review. J Diab Investig. 2020;11:946–55. Article  CAS  Google Scholar  * Durrani L, Ejaz S, Tavares LB, Mohyeldin M, Abureesh D, Boorenie M, et al. Correlation


between high serum ferritin level and gestational diabetes: a systematic review. Cureus. 2021;13:e18990. PubMed  PubMed Central  Google Scholar  * Jung J, Rahman MM, Rahman MS, Swe KT, Islam


MR, Rahman MO, et al. Effects of hemoglobin levels during pregnancy on adverse maternal and infant outcomes: a systematic review and meta-analysis. Ann N. Y Acad Sci. 2019;1450:69–82.


Article  PubMed  Google Scholar  * Guideline: Daily iron and folic acid supplementation in pregnant women. In: _Guideline: Daily Iron and Folic Acid Supplementation in Pregnant Women_.


Geneva 2012. * Liu L, Yan F, Yan H, Wang Z. Impact of iron supplementation on gestational diabetes mellitus: A literature review. Diab, Obes Metab. 2022;25:342–53. Article  Google Scholar  *


Puntarulo S. Iron, oxidative stress and human health. Mol Asp Med. 2005;26:299–312. Article  CAS  Google Scholar  * Zein S, Rachidi S, Shami N, Sharara I, Cheikh-Ali K, Gauchez A-S, et al.


Association between iron level, glucose impairment and increased DNA damage during pregnancy. J Trace Elem Med Biol. 2017;43:52–57. Article  CAS  PubMed  Google Scholar  * Erbagci MO, Tuna


G, Kose S, Dal-Bekar NE, Akis M, Kant M, et al. Association between early oxidative DNA damage and iron status in women with gestational diabetes mellitus. Reprod Toxicol. 2021;103:171–80.


Article  CAS  PubMed  Google Scholar  * Gautam S, Alam F, Moin S, Noor N, Arif SH. Role of ferritin and oxidative stress index in gestational diabetes mellitus. J Diab Metab Disord.


2021;20:1615–9. Article  CAS  Google Scholar  * Montonen J, Boeing H, Steffen A, Lehmann R, Fritsche A, Joost HG, et al. Body iron stores and risk of type 2 diabetes: results from the


European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. Diabetologia. 2012;55:2613–21. Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang X, Fang X,


Zheng W, Zhou J, Song Z, Xu M, et al. Genetic support of a causal relationship between iron status and type 2 diabetes: a mendelian randomization study. J Clin Endocrinol Metab.


2021;106:e4641–e4651. Article  PubMed  PubMed Central  Google Scholar  * International Association of D, Pregnancy Study Groups Consensus P, Metzger BE, Gabbe SG, Persson B, Buchanan TA,


Catalano PA, Damm P, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diab Care.


2010;33:676–82. Article  Google Scholar  * Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function


from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9. Article  CAS  PubMed  Google Scholar  * Cederholm J, Wibell L. Insulin release and peripheral


sensitivity at the oral glucose tolerance test. Diab Res Clin Pr. 1990;10:167–75. Article  CAS  Google Scholar  * Jia W. Status of insulin resistance in Chinese population. Int J Endocrinol


Metab. 2002;22:264. Google Scholar  * WHO. Definition and diagnosis of diabetes. 2006. * Cheng Y, Li T, He M, Liu J, Wu K, Liu S, et al. The association of elevated serum ferritin


concentration in early pregnancy with gestational diabetes mellitus: a prospective observational study. Eur J Clin Nutr. 2020;74:741–8. Article  CAS  PubMed  Google Scholar  * Pandey R,


Singh U, Solanki V, Mehrotra S. Association of serum ferritin level in early second trimester of pregnancy with development of gestational diabetes mellitus: a prospective observational


study. J Obstet Gynaecol India. 2023;73:235–41. Article  CAS  PubMed  PubMed Central  Google Scholar  * Sharifi F, Ziaee A, Feizi A, Mousavinasab N, Anjomshoaa A, Mokhtari P Serum ferritin


concentration in gestational diabetes mellitus and risk of subsequent development of early postpartum diabetes mellitus. _Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy_.


2010. * Hershenfeld S, Ye C, Hanley AJ, Connelly PW, Zinman B, Retnakaran R. Serum ferritin and glucose homeostasis in women with recent gestational diabetes. Can J Diab. 2019;43:567–72.


Article  Google Scholar  * Källner K, Krook R, Sandberg A-S, Hulthén L, Andersson-Hall U, Holmäng A. Interaction of iron homeostasis and fatty acid metabolism in the development of glucose


intolerance in women with previous gestational diabetes mellitus. Nutrients. 2023;15:3214. Article  PubMed  PubMed Central  Google Scholar  * Cancado RD. Iron deficiency anemia in women:


pathophysiological, diagnosis, and practical management. Rev Assoc Med Bras (1992). 2023;69:e2023S2112. Article  Google Scholar  * Cooksey RC, Jouihan HA, Ajioka RS, Hazel MW, Jones DL,


Kushner JP, et al. Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology. 2004;145:5305–12. Article  CAS  PubMed 


Google Scholar  * Feng Y, Qi R, Xu M, Shen Z, Li M. Dietary iron supplements may affect stress adaptation and aggravate stress hyperglycemia in a rat model of psychological stress.


Nutrition. 2012;28:691–7. Article  CAS  PubMed  Google Scholar  * Swaminathan S, Fonseca VA, Alam MG, Shah SV. The role of iron in diabetes and its complications. Diab Care. 2007;30:1926–33.


Article  CAS  Google Scholar  * Bo S, Menato G, Villois P, Gambino R, Cassader M, Cotrino I, et al. Iron supplementation and gestational diabetes in midpregnancy. Am J Obstet Gynecol.


2009;201:158 e151–156. Article  Google Scholar  * Georgieff MK, Krebs NF, Cusick SE. The benefits and risks of iron supplementation in pregnancy and childhood. Annu Rev Nutr. 2019;39:121–46.


Article  CAS  PubMed  PubMed Central  Google Scholar  * Si S, Shen Y, Xin X, Mo M, Shao B, Wang S, et al. Hemoglobin concentration and iron supplement during pregnancy were associated with


an increased risk of gestational diabetes mellitus. J Diab. 2021;13:211–21. Article  CAS  Google Scholar  * Zhang Y, Xu S, Zhong C, Li Q, Wu M, Zhang G, et al. Periconceptional iron


supplementation and risk of gestational diabetes mellitus: A prospective cohort study. Diab Res Clin Pr. 2021;176:108853. Article  CAS  Google Scholar  * Petry CJ. Iron supplementation in


pregnancy and risk of gestational diabetes: a narrative review. Nutrients. 2022;14:4791. Article  CAS  PubMed  PubMed Central  Google Scholar  * McClean S, Farrar D, Kelly CA, Tuffnell DJ,


Whitelaw DC. The importance of postpartum glucose tolerance testing after pregnancies complicated by gestational diabetes. Diabet Med. 2010;27:650–4. Article  CAS  PubMed  Google Scholar  *


Ogonowski J, Miazgowski T. The prevalence of 6 weeks postpartum abnormal glucose tolerance in Caucasian women with gestational diabetes. Diab Res Clin Pr. 2009;84:239–44. Article  CAS 


Google Scholar  * Carson MP, Frank MI, Keely E. Original research: postpartum testing rates among women with a history of gestational diabetes–systematic review. Prim Care Diab.


2013;7:177–86. Article  Google Scholar  * Butalia S, Donovan L, Savu A, Johnson J, Edwards A, Kaul P. Postpartum diabetes testing rates after gestational diabetes mellitus in canadian women:


a population-based study. Can J Diab. 2017;41:613–20. Article  Google Scholar  * Baptiste-Roberts K, Barone BB, Gary TL, Golden SH, Wilson LM, Bass EB, et al. Risk factors for type 2


diabetes among women with gestational diabetes: a systematic review. Am J Med. 2009;122:207–214.e204. Article  PubMed  PubMed Central  Google Scholar  * Liu Z, Zhang Q, Liu L, Liu W. Risk


factors associated with early postpartum glucose intolerance in women with a history of gestational diabetes mellitus: a systematic review and meta-analysis. Endocrine. 2023;82:498–512.


Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS The authors acknowledge the contributions of all the participants. This work was partly supported by the National


Key Research and Development Program of China (2021YFC2501600; 2021YFC2501601), National Natural Science Foundation of China (82170879), Shanghai Science and Technology Commission Foundation


(21Y11904800; 23ZR1451500), Shanghai Songjiang District Science and Technology Research Program (21SJKJGG51). AUTHOR INFORMATION Author notes * These authors contributed equally: Na Li,


Shuai Yan, Jianrong Weng. AUTHORS AND AFFILIATIONS * Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai,


200080, China Na Li, Shuai Yan, Guiling Liang, Yujia Gong, Yanmei Su, Xiaohui Wei, Wenqian Ren, Qin Zhen, Jiali Zhu, Fang Liu & Yufan Wang * Department of Obstetrics and Gynecology,


Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China Jianrong Weng * National Clinical Research Center for Eye Diseases, Shanghai General


Hospital, 100 Haining Rd, Shanghai, 200080, China Fang Zhang Authors * Na Li View author publications You can also search for this author inPubMed Google Scholar * Shuai Yan View author


publications You can also search for this author inPubMed Google Scholar * Jianrong Weng View author publications You can also search for this author inPubMed Google Scholar * Guiling Liang


View author publications You can also search for this author inPubMed Google Scholar * Yujia Gong View author publications You can also search for this author inPubMed Google Scholar *


Yanmei Su View author publications You can also search for this author inPubMed Google Scholar * Xiaohui Wei View author publications You can also search for this author inPubMed Google


Scholar * Wenqian Ren View author publications You can also search for this author inPubMed Google Scholar * Qin Zhen View author publications You can also search for this author inPubMed 


Google Scholar * Jiali Zhu View author publications You can also search for this author inPubMed Google Scholar * Fang Liu View author publications You can also search for this author


inPubMed Google Scholar * Fang Zhang View author publications You can also search for this author inPubMed Google Scholar * Yufan Wang View author publications You can also search for this


author inPubMed Google Scholar CONTRIBUTIONS All authors contributed to the study conception and design. NL, SY, and JRW were responsible for designing the project, conducting the search,


extracting and analyzing data, interpreting results, and updating reference. GLL, YMS, XHW, WQR, QZ, JLZ and FL were responsible for extracting and analyzing data, interpreting results, and


updating reference. The first draft of the manuscript was written by Na Li. YFW and FZ revised and edited the manuscript. All authors read and approved the final manuscript. CORRESPONDING


AUTHORS Correspondence to Fang Zhang or Yufan Wang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer


Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTAL TABLE RIGHTS AND PERMISSIONS OPEN ACCESS


This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and


reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you


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copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Li, N., Yan, S., Weng, J. _et al._ Association of


mid-pregnancy ferritin levels with postpartum glucose metabolism in women with gestational diabetes. _Nutr. Diabetes_ 14, 77 (2024). https://doi.org/10.1038/s41387-024-00338-7 Download


citation * Received: 10 May 2024 * Revised: 12 September 2024 * Accepted: 18 September 2024 * Published: 27 September 2024 * DOI: https://doi.org/10.1038/s41387-024-00338-7 SHARE THIS


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