Maternal systemic iron homeostasis in diabetes-in-pregnancy

Pregnancy causes an increase in central corneal thickness (CCT) and a reduction in intraocular pressure (IOP), especially in the third trimester. However, there is very limited published data regarding CCT and IOP in gestational diabetes mellitus (GDM) on diet control. This study is aimed to compare the means of CCT and IOP between pregnant women with GDM on diet control, healthy pregnant women, and healthy non-pregnant women. This is a comparative cross-sectional study. A total of 184 women were recruited and divided into the following three groups: 61 pregnant women with GDM on diet control, 63 healthy pregnant women, and 60 healthy non-pregnant women as control. All subjects have undergone ocular examination during their 36-40 weeks of gestation. CCT measurement was done using a specular microscope and IOP measurement using a non-contact tonometer. Data from the right eye were analyzed. The mean age was 32 (4.0)years in GDM on diet control, 29 (3.0)years in healthy pregnant women, and 27 (5.4)years in healthy non-pregnant women. The number of gravidas was 2.5 (0.8) in women with GDM on diet control and 2.3 (0.8) in healthy pregnant women. There was a significant difference (p<0.05) in the mean CCT in women with GDM on diet control compared to healthy pregnant and healthy non-pregnant women. The mean IOP is significantly lower in both pregnant women with GDM on diet control and healthy pregnant groups, compared to the healthy non-pregnant women group. Women with GDM showed significantly thicker mean CCT than healthy pregnant and non-pregnant women. The mean IOP is significantly lower in both pregnant women with GDM on diet control and healthy pregnant groups, compared to the healthy non-pregnant women group.

Objective : To compare the fetal iron metabolism in maternal type 1 and gestational diabetes mellitus (GDM) with non-diabetic pregnancies. Methods: Iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (STfR) and hemoglobin concentration were measured in both maternal and cord blood of 91 pregnant women and soluble transferrin receptor (TfR-F) Index was calculated. Cord pH and erythropoietin were also measured. Thirty-three women had GDM and 29 had type 1 diabetes and these were compared with 29 non-diabetic pregnancies as controls. Diabetic subjects and control group who fulfilled the inclusion criteria were recruited consecutively according to the admission time to the hospital. Results : The median duration of type 1 diabetes was 5(2-18) years and for GDM was 6(3-9) months. The controls were younger and had lower body mass index (BMI) compared with the study groups. The maternal hemoglobin concentration during pregnancy and immediately after delivery was not statistically different among diabetics and control groups. The infants of diabetic mothers had higher birth weight than control group, but it was statistically significant only in the GDM group (P= 0.025). There wasn't any statistically significant difference in measured parameters between infants of GDM and control group, although the GDM group seemed to have lower serum ferritin level. Infants of type1 diabetes had significantly higher concentration of hemoglobin (15.9 vs 14.6 g/dl, p=0.017), lower ferritin (28.1 vs 64ng/ml, p=0.002) and considerable higher TfR-F index (0.59 vs 0.48, p=0.05) than control group. The incidence of hypoglycemia was also more in the type 1 diabetic group (p=0.004). There were 3 women in GDM and 6 women in type 1 diabetes group with poor glycemic control. Their infants had higher Hb, erythropoietin, TfR-F index and lower ferritin and iron in cord blood. Conclusion: This study confirms that iron stores (Fe and ferritin) are lower at birth in infants of women with type 1 diabetes and the influence of type 1 diabetes on fetal iron status is more prominent than gestational diabetes.

Objective To investigate the role of hemoglobin (Hb),red blood cell count (RBC) and hematocrit (HCT) during the first trimester in predicting the occurrence of gestational diabetes mellitus (GDM) in the third trimester in nonanemic women in Kunming.Methods A prospective study was carried out.Routine blood tests were performed in 1189 nondiabetic singleton pregnant Chinese women at their initial prenatal healthcare before 14 gestational weeks in the First Affiliated Hospital of Kunming Medical University from January 1,2008 to December 31,2009.They were divided into four groups by quartiles of Hb,RBC and HCT levels respectively.Differences of GDM incidence at the third trimester were compared among groups.Kollmogorov Smirnov test was used to detect normal distribution of Hb,RBC and HCT results.Differences between rates of groups were detected by Chi-square test.Independent risk factors of GDM were screened by Logistic regression analysis.Results The incidence of GDM at the third trimester increased as quartile categories of Hb,RBC and HCT ascended.The GDM incidence (13.1 ％,34/259) of ≥75th Hb group was higher than that of ＜ 25th group (5.9 ％,18/304,x2 =8.53,P＜ 0.0 1),25th ～ group (9.2 ％,30/326,x2=4.18,P＜0.05) and 50th～ group (9.3％,28/300,x2=3.96,P＜0.05).The GDM incidence (11.7 ％,34/290) of 50th～ RBC group (RBC≥4.44 × 1012/L) was higher than that of ＜25th group (6.3％,19/304,x2=5.30,P＜0.05),25th～ group (7.0％,21/298,x2 =3.93,P＜0.05); and the GDM incidence (12.1％,36/297) of ≥75th group was also higher than that of ＜25th group (6.3％,19/304,x2 =6.49,P＜0.05),25th～ group (7.0％,21/298,x2=3.85,P＜0.05).The GDM incidence of ＜25th HCT group (5.3％,16/303) was lower than that of 25th～ group (9.3％,29/311,x2=7.04,P＜0.01),50th～ group (10.8％,31/287,x2=3.93,P＜0.05) and ≥75th group (11.8％,34/288,x2=6.49,P＜0.05).Logistic regression analysis showed that Hb (OR=1.031,95％ CI:1.010-1.052),RBC (OR=2.286,95％CI:1.318-3.963) and HCT (OR=1.106,95％ CI:1.037-1.179) were independent risk factors of GDM (all P＜0.05).Conclusions High maternal Hb,RBC and HCT levels in the first trimester could be used in predicting GDM in pregnant women in Kunming area. Key words: Pregnant women; Hemaglobins; Erythrocyte count; Hematocrit; Diabetes,gestational

BackgroundThe information about macular and retinal nerve fibre layer (RNFL) thickness in women with gestational diabetes mellitus (GDM) is scarce. GDM is a risk factor for development of type 2 diabetes mellitus.PurposeThe purpose of this study was to evaluate mean macular and RNFL thickness in pregnant women with GDM in a teaching institution in Malaysia. We also analyzed the association of age, HbA1c level, duration of GDM, type of treatment, family history, previous history of GDM and spherical equivalent with the macular and RNFL thickness.Patients and MethodsThis was a prospective and cross-sectional study involving 78 pregnant women with GDM, 72 healthy pregnant and 70 healthy non-pregnant women. The study was conducted in Hospital Universiti Sains Malaysia from 2016 to 2018. Macular and RNFL thickness were measured during the third trimester using spectral-domain optical coherence tomography. Age, HbA1c level, duration of GDM, type of treatment, family history, previous history of GDM and spherical equivalent were analysed.ResultsThe mean macular thickness was 236.08 (16.44) µm, 237.26 (22.42) µm and 240.66 (20.95) µm for GDM, healthy pregnant, and healthy non-pregnant women. The mean RNFL thickness was 97.27 (9.14) µm, 99.83 (12.44) µm and 97.97 (10.07) µm for GDM, healthy pregnant, and healthy non-pregnant women. There was no significant difference in the mean macular and RNFL thickness in pregnant women with GDM when compared to the control groups (p>0.05). Age, HbA1c, duration of diabetes, treatment received, history of GDM and spherical equivalent did not show significant association with mean macular and retinal thickness (p>0.05).ConclusionPregnant women with GDM have similar thickness of the macular and RNFL with the healthy pregnant and healthy non-pregnant women. Age, HbA1c, duration of diabetes, treatment received, history of GDM and spherical equivalent showed no significant association with mean macular and retinal thickness in pregnant women with GDM.

OBJETIVE: To evaluate the association between the use of iron salts during the first two trimesters of gestation in non-anemic women and the development of gestational diabetes mellitus. METHODS: The study used maternal data from the 2015 Pelotas Birth Cohort. All non-anemic women at the 24th week of gestation (n = 2,463) were eligible for this study. Gestational diabetes mellitus was self-reported by women. Crude and adjusted logistic regression were performed considering level of significance = 0.05. RESULTS: Among the women studied, 69.7% were exposed to prophylactic iron supplementation in the first two trimesters of gestation. The prevalence of gestational diabetes mellitus among those exposed was 8.7% (95%CI: 7.4–10.1) and 9.3% (95%CI: 7.4–11.6) among those who were not exposed. Iron supplementation was not associated with increased risk of gestational diabetes mellitus in crude (OR = 0.9; 95%CI: 0,7–1,3) and adjusted analysis (OR = 1.1; 95%CI :0,8–1,6). CONCLUSIONS: The results suggest that routine iron use in non-anemic pregnant women does not increase the risk of developing gestational diabetes. This evidence supports the existing national and international guidelines, in which prophylactic iron supplementation is recommended for all pregnant women as soon as they initiate antenatal care in order to prevent iron deficiency anemia.

BackgroundThis study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk.MethodsThis retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14–16 weeks’ gestation for Hp genotyping. GDM was diagnosed between 24–28 weeks’ gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk.ResultsWomen who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2–2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk.ConclusionIncreased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2–2 genotype.

Usefulness of Reticulocyte Hemoglobin Equivalent for Diagnosis of Iron Deficiency

Background: Routine iron supplementation for all pregnant women in order to reduce adverse neonatal outcomes has been a standard practice in developing countries, including Thailand. However, there is evidence that excess iron can affect glucose metabolism and may increase risk of gestational diabetes mellitus (GDM). This study aims to investigate the association of iron supplementation starting from early gestation and the risk of GDM in non-anemic women. Methods: This retrospective cohort study included non-anemic pregnant Thai women who received their first antenatal care and delivered at Vajira Hospital (Bangkok, Thailand) during January 2008 to December 2009. All pregnant women underwent oral glucose tolerance test during gestational weeks 24 - 28. The proportions of ongoing GDM and birth outcomes were compared between the early oral iron supplementation group (before 16 completed weeks) and the control group (after 16 weeks). Results: There were 1,935 non-anemic pregnant women, 966 in the early supplement group and 969 in the control group. The early supplement group had significantly higher prevalence of GDM than the control group did (9.7% vs. 5.6%, RR: 1.83; 95% CI: 1.29 - 2.59). No significant differences in maternal anemia, gestational age at birth, or neonatal birth weight were observed between groups. Conclusions: Early antenatal iron supplementation in non-anemic pregnant women was found to be associated with significantly increased risk of GDM. J Endocrinol Metab. 2018;8(6):139-143 doi: https://doi.org/10.14740/jem543

To compare oxidative stress (OS) markers in the saliva, gingival crevicular fluid (GCF), and serum samples of pregnant women with gestational diabetes (GDM) and healthy pregnant women and to investigate the association between periodontal health/diseases and OS and GDM. Eighty women with GDM and 80 healthy pregnant women were included in the study. Medical and clinical anamnesis was obtained from all the pregnant women included in the study, and their plaque index (PI), gingival index (GI), bleeding on probing (BoP), probing pocket depth (PPD), and clinical attachment level (CAL) measurements were performed. GCF, saliva, and serum samples were collected for the measurements of the local and systemic total antioxidant status (TAS) and total oxidant status (TOS). Clinical periodontal parameters were found to be significantly higher in the GDM group compared to the control group. The serum and saliva TAS, TOS, and TAS/TOS values were significantly lower in the GDM group than in the control group. In the analysis of the GCF samples, the mean TAS and TAS/TOS values were significantly lower and the TOS value was significantly higher in the GDM group than in the control group. The multivariate reduced model indicated that gravidity, salivary TAS/TOS, and GCF TAS were significant independent variables in the development of GDM (p < .05). Our results indicated that the OS of serum, saliva, and GCF samples increased in patients with GDM compared to healthy pregnant women. The role of local OS parameters in GDM may be associated with elevated clinical periodontal parameters.

A gestational diabetes mellitus (GDM) diagnosis during pregnancy means an increased risk of developing type 2 diabetes later in life. By following up with women after GDM we aimed to examine the relationship between iron parameters, individual fatty acids (FAs) and desaturases in the development of impaired glucose metabolism (IGM). Based on an oral glucose tolerance test (OGTT), six years after GDM, 157 women were grouped as having normal glucose tolerance (NGT) or IGM. Fasting serum FAs, activity of desaturases and iron parameters (ferritin, transferrin, iron, soluble transferrin receptor, total iron binding capacity, hepcidin) were measured, and clinical and anthropometric measurements taken. Soluble transferrin receptor was higher in the IGM group compared to the NGT group (3.87 vs. 3.29 mg/L, p-value = 0.023) and associated positively with saturated FAs and negatively with monounsaturated FAs in the IGM group (adjusted for BMI, age and high sensitivity C-reactive protein; p-value < 0.05). Iron, as well as transferrin saturation, showed a positive association with MUFAs and desaturase activity. These associations were not seen in the NGT group. These results suggest that iron homeostasis and FA metabolism interact in the development of glucose intolerance in women with previous GDM.

BackgroundThe use of traditional historic risk factors to identify gestational diabetes mellitus (GDM) will miss half of women with gestational diabetes mellitus. Our aim was to evaluate whether impaired glucose tolerance is a risk factor for vaginal candidiasis in pregnant women.Patients and MethodsIn a cross-sectional study, we compared the prevalence of impaired glucose tolerance in 64 pregnant women with vaginal candidiasis (positive microscopy) and 59 Candida-negative control subjects. Subjects underwent standardized 75-gram oral glucose tolerance testing between the 24th and 28th weeks of their pregnancies. Patients were included only if they had no known diabetes mellitus or historic risk factors for gestational diabetes mellitus, and had not been receiving antibiotic or steroid therapy. We compared glucose levels at fasting, 30 minutes, 60 minutes and 120 minutes, and perinatal and neonatal outcomes in the two groups.ResultsThere were no statistical differences between cases and controls in demographic characteristics. Glucose concentrations were higher in pregnant women with vaginal candidiasis than in control subjects at fasting (89 vs. 84 mg/dL, P=0.021), 30 minutes (139 vs. 126 mg/dL, P=0.050), and 60 minutes (124 vs. 106 mg/dL, P=0.018) after intake of 75 gram of glucose. The two groups did not differ in glucose level at 120 minutes after glucose administration. Gestational diabetes prevalence was 3.1% and 3.4% in the study and control group, respectively (P=0.274).ConclusionThe tolerance to glucose in pregnant women with vaginal candidiasis seems discretely impaired.

Background: Approximately 25–38% of chronic kidney disease (CKD) patients with anemia suffer absolute or functional iron deficiency. This deficiency is estimated and monitored primarily through two iron indices, viz., transferrin saturation (TSAT) and serum ferritin. However, both these parameters suffer from several lacunae and search continues to establish more true measures. This study enquires into the role of soluble transferrin receptors (sTfR) and ratio of sTfR and log ferritin index (sTfR index) as potential measures of the true iron status in patients. Material and Methods: This prospective cross-sectional study comprised a total of 126 CKD patients with anemia on erythropoietin (EPO) undergoing hemodialysis (HD). Of these 126 patients, 55 had iron deficiency anemia (IDA). Estimations of serum iron, TSAT, serum ferritin, and sTfR and sTfR, indices were performed in each patient. Bone marrow aspiration (BMA) was carried out to determine cellularity, cytomorphology, and myeloid: erythroid (M/E) ratio, and was stained with Prussian blue stain. The results of the bone marrow iron status were taken as the gold standard. Subsequently, receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminative power of the sTfR and sTfR indices for evaluation of iron status in patients with CKD. Results: The cut-off value of sTfR index at its maximum sensitivity (71.8%) and specificity (62%) was found to be 1.39, whereas that of sTfR at its maximum sensitivity (63.6%) and specificity (64.8%) was 3.00. Statistically significant correlations were found between sTfR index (Pearson correlation (r) = –0.379) and serum iron (r = –0.38; P < 0.01), TSAT (r = –0.31; P < 0.01), and serum ferritin (r = –0.399; P < 0.01). sTfR was found to correlate significantly (r = –0.445) with serum iron (P < 0.01), TSAT (r = –0.365; P < 0.01), and hemoglobin (r = –0.179; P = 0.04) but not with serum ferritin (r = 0.12; P = 0.153). Conclusion: sTfR and sTfR index values are useful tools for assessment of iron status in patients with CKD, however, they are at best complementary to the existing indices of serum ferritin and TSAT. Between sTfR and sTfR index, the latter has a greater discriminating power.

Objective This study aimed to investigate relationships between blood inflammatory and metabolic biomarkers in pregnant Chinese women with gestational diabetes mellitus (GDM) in Southwest China and to compare the contributions of blood inflammatory indicators to GDM identification. Subjects and methods In total, 1,347 pregnant women were divided by gestational week into early-, middle- and late-pregnancy groups. Fasting samples were collected for complete blood count (CBC) and biochemical indicator measurements. Receiver operating characteristic (ROC) curves were used to predict GDM. Multivariate logistic regression was used to examine the associations between blood inflammatory indicators and GDM prevalence in pregnant women. Results Significant differences were found in blood inflammatory indicators and metabolic markers in different pregnancy trimesters. For the pregnant women with GDM, FPG, 1 h-PG, 2 h-PG levels, NLR and PLR, WBC and neutrophil counts were statistically differences when compared with non-GDM groups. ROC curve analysis indicated that the NLR, PLR, WBC and neutrophil counts have predictive value for GDM from 24–28 gestational weeks. The FPG levels in 24th–28th weeks of pregnant women were positively correlated with the NLR, PLR, 1 h-PG, 2 h-PG levels and negatively correlated with lymphocyte count. Following adjustment for the age, PLR, and FPG level, multivariate logistic regression showed that the NLR was an independent factor predicting GDM in the 24th–28th weeks of pregnancy. Conclusion The blood inflammatory indicators NLR, PLR, and WBC and neutrophil counts were higher in GDM women than in healthy pregnant women, suggesting that blood inflammatory indicators are associated with GDM.

We aimed to determine the role of placental A Disintegrin and Metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and maternal serum ADAMTS5, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) levels at 24–28th gestational weeks in GDM. This study included 57 patients, who had been diagnosed as having GDM at their 24–28th gestational week, and 29 controls. The maternal blood samples were collected at the 24-28th gestational week and ADAMTS5 was studied with the enzyme-linked immunosorbent assay (ELISA) method, whereas an automated colorimetric method was used to study TAS, TOS, and OSI. The level of ADAMTS5 in maternal serum of patients with GDM were significantly lower than the controls (p = .017); whereas TOS and OSI levels were significantly higher (p = .003 and p = .008). Multivariable logistic regression analysis revealed ADAMTS5 and TOS levels were independently associated with adverse perinatal outcomes (p = .004 and p = .018). We found that serum ADAMTS5 levels decreased and TOS level increased in GDM pregnant at 24–28th gestational weeks. In addition, we found that increased levels of serum ADAMTS5 and decreased TOS levels at 24–28th weeks were associated with adverse perinatal outcomes independent of the mode of treatment in GDM.Impact statementWhat is already known on this subject? Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. The insulin resistance, which starts at the 24–28th gestational weeks, increases during gestation. GDM increases maternal complications like preeclampsia, cesarean rate, cardiovascular disease, obesity, and diabetes after pregnancy; and neonatal complications like macrosomia, hypoglycemia, hyperbilirubinemia, delivery trauma, shoulder dystocia, and adult-onset obesity, and diabetes.What the results of this study add? A significant relationship between ADAMTS5, TOS levels and adverse perinatal outcome. insulin resistance and was observed.What the implications are of these findings for clinical practice and/or further research? Based on this finding, we concluded that increased levels of oxidative stress and decreased ADAMTS5 levels are associated with GDM and predictive for adverse perinatal outcomes. The results of the present study were consistent with the previous reports and indicated that increased oxidative stress in GDM patients are related to adverse perinatal outcomes.

The aim of this study was to compare the differences in salivary metabolites between pregnant women with gestational diabetes mellitus (GDM), healthy pregnant women (HPW), and healthy non-pregnant women (HNPW), and analyze the possible associations between the identified metabolites and gingivitis. The study included women with GDM (n = 9, mean age 28.9 ± 3.6 years, mean gestational age 30.1 ± 3.2 weeks), HPW (n = 9, mean age 27.9 ± 3.0 years, mean gestational age 28.6 ± 4.7 weeks), and HNPW (n = 9, mean age 27.7 ± 2.1 years). Saliva samples were collected from all participants and were analyzed with LC-MS/MS-based untargeted metabolomic analysis. Metabolite extraction, qualitative and semi-quantitative analysis, and bioinformatics analysis were performed to identify the differential metabolites and metabolic pathways between groups. The identified differential metabolites were further analyzed in an attempt to explore their possible associations with periodontal health and provide evidence for the prevention and treatment of periodontal inflammation during pregnancy. In positive ion mode, a total of 2,529 molecular features were detected in all samples, 166 differential metabolites were identified between the GDM and HPW groups (89 upregulated and 77 downregulated), 823 differential metabolites were identified between the GDM and HNPW groups (402 upregulated and 421 downregulated), and 647 differential metabolites were identified between the HPW and HNPW groups (351 upregulated and 296 downregulated). In negative ion mode, 983 metabolites were detected in all samples, 49 differential metabolites were identified between the GDM and HPW groups (29 upregulated and 20 downregulated), 341 differential metabolites were identified between the GDM and HNPW groups (167 upregulated and 174 downregulated), and 245 differential metabolites were identified between the HPW and HNPW groups (112 upregulated and 133 downregulated). A total of nine differential metabolites with high confidence levels were identified in both the positive and negative ion modes, namely, L-isoleucine, D-glucose 6-phosphate, docosahexaenoic acid, arachidonic acid, adenosine, adenosine-monophosphate, adenosine 5'-monophosphate, xanthine, and hypoxanthine. Among all pathways enriched by the upregulated differential metabolites, the largest number of pathways were enriched by four differential metabolites, adenosine, adenosine 5'-monophosphate, D-glucose 6-phosphate, and adenosine-monophosphate, and among all pathways enriched by the downregulated differential metabolites, the largest number of pathways were enriched by three differential metabolites, L-isoleucine, xanthine, and arachidonic acid. Untargeted metabolomic analysis of saliva samples from pregnant women with GDM, HPW, and HNPW identified nine differential metabolites with high confidence. The results are similar to findings from previous metabolomics studies of serum and urine samples, which offer the possibility of using saliva for regular noninvasive testing in the population of pregnant women with and without GDM. Meanwhile, the associations between these identified differential metabolites and gingivitis need to be further validated by subsequent studies.