Placental lactogen, placental growth factor, insulin resistance in early pregnancy and risk for gestational diabetes

Background and aims. Placental hormones and proteins are important regulators of insulin resistance during pregnancy. However, the data concerning the assosiation between placental lactogen (PL) and placental growth factor (PLGF) level in early pregnancy and further development of gestational diabetes mellitus (GDM) are limited and incostintent. The aim of this study was to compare the level of these two placental proteins and homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy among women diagnosed with and without GDM months later.Materials and methods. A nested case-control study was conducted in a prospective cohort of pregnant women. Among them, 78 incident GDM cases were identified and 95 women who were not diagnosed with GDM were randomly selected as a control group. Blood was sampled for measurements of PL, PLGF, fasting plasma glucose and insulin at 8-14 weeks of pregnancy. All the women underwent oral glucose tolerance test (OGTT) at 24-32 weeks. GDM was diagnosed according to the International Association of Diabetes In Pregnancy Study Groups (IADPSG) recommendations (fasting glucose ≥5.1 mmol / l and / or 1 hour ≥10.0 mmol / l and / or 2 hours ≥8.5 mmol / L). The maternal and neonatal anthropometric parameters were also measured. Statistical analysis included Student's t-test, logistic regression and Pearson's correlation.Results. There was no difference between GDM and control groups in the mean levels of PL (0,70 +/- 0,53 vs 0,81 +/- 0,58 mg/L, р =0,215 ) and PLGF (60,7 +/- 169.6 vs 46,6+105,6 pg/ml, р=0,503). Women with GDM were older (30.2 +/- 3.9 vs 28.4 +/- 4.7 years, p = 0.008), had higher first trimester body mass index (BMI) (25.2 +/- 5.2 vs 23.1 +/- 4.6 kg/m2, р = 0.006), higher levels of insulin (10.3 +/- 5.5 vs 7.9 +/- 3.9 mU/L, p = 0,007) and HOMA-IR ( 2.17 +/- 1.1 vs 1.7 +/- 0.9, p = 0,007) compared to the control group. Women with GDM also had a higher level of fasting plasma glucose (4.8 + 0.6 and 4.6 + 0,5 mmol/L, p = 0.063), although the difference did not reach statistical significance. HOMA-IR was positively associated with the development of GDM (OR: 1.62, 95% CI: 1.12 - 2.34, P = 0.01) and the association retained under a multivariable analysis controlling for age and BMI (OR: 1.59, 95% CI: 1.04 - 2.45, P = 0.033). Maternal PL and PLGF were not related to the results of OGTT, HOMA-IR or neonatal anthropometry. A positive correlation between PL level and gestational age at the time of blood sampling was observed (r = 0.657, p <0.001).Conclusion. Serum concentrations of PL and PLGF in pregnant women at 8-14 weeks’ gestation were not associated with HOMA-IR and later development of GDM. Higher HOMA-IR score in early pregnancy is significantly associated with an elevated risk for GDM.

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Expression of Dual-Specificity Phosphatase 9 in Placenta and Its Relationship with Gestational Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2019/1963178 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Qiang Wei ◽

Xiaomin Pu ◽

Li Zhang ◽

Yi Xu ◽

Meifan Duan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Body Mass Index ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Plasma Glucose ◽

Mrna Levels ◽

Gestational Week

Introduction. The aim of the present study was to examine placental levels of DUSP9 mRNA and protein and to investigate the potential role of DUSP9 in the development of gestational diabetes mellitus (GDM). Methods. Placental tissues from pregnant women with GDM (n=17) and normal healthy pregnant women (n=16) were collected at delivery. The expression of DUSP9 mRNA in placental tissue was analyzed by real-time PCR, while the expression of DUPS9 protein was evaluated by immunohistochemistry and western blot. Differences in the expression levels of DUSP9 mRNA and protein between the two groups were assessed, as well as potential correlations between DUSP9 mRNA expression levels and relevant clinical indicators. Results. Blood glucose levels were significantly higher in the GDM group than in the control group, based on an oral glucose tolerance test. DUSP9 protein was expressed in the placental cytotrophoblasts in both groups, and placental levels of DUSP9 protein and mRNA were significantly higher in women with GDM. Placental DUSP9 mRNA levels in all 33 women correlated moderately with delivery gestational week (R=0.465, P=0.006), fasting plasma glucose (R=0.350, P=0.046), 1-hour postload plasma glucose (R=0.363, P = 0.038), and 2-hour postload plasma glucose (R=0.366, P=0.036), but not with maternal age, preconception body mass index, prenatal body mass index, or neonatal birth weight. Multiple linear regression analysis indicated that delivery gestational week was an influence factor of DUSP9 mRNA levels (β1=0.026, P<0.05). Conclusions. DUSP9 upregulation in the placenta of GDM pregnant women may promote insulin resistance, which may correlate with the occurrence of GDM. But there is still possibility that DUSP9 upregulation was the results of insulin resistance and/or hyperglycemia. Further research is needed to explore the role of DUSP9 in GDM.

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PRACTICAL SCREENING FOR DIABETES MELLITUS IN PREGNANT WOMEN

Acta Endocrinologica ◽

10.1530/acta.0.075s011 ◽

1974 ◽

Vol 77 (3_Suppl) ◽

pp. S11-S24 ◽

Cited By ~ 29

Author(s):

Eigil Guttorm

Keyword(s):

Pregnant Women ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Screening Method ◽

Control Group ◽

List Type ◽

Fasting Plasma ◽

Class B ◽

Close Relatives ◽

In Pregnancy

ABSTRACT A prospective and consecutive investigation of 1697 pregnant women without earlier known diabetes and a retrospective investigation of 120 pregnant diabetics (White class A: 94, White class B: 26), has been performed. It was found that: the most useful criteria of potential diabetics were: 1) the presence of diabetes in close relatives, diagnosed before the age of 40 years, 2) the presence of obesity in the patients, defined as 20 per cent overweight or more just before pregnancy, 3) previous delivery of a big baby, defined as a baby with birthweight ≦ 4500 g. Of the 1697 pregnant women 8 per cent were potential diabetics and in 8 per cent glucosuria was found. pregnant women with glucosuria and potential diabetics defined as above had a higher risk of having a diabetic OGTT than other pregnant women. A diabetic OGTT was found with falling incidence in the groups: potential diabetics with glucosuria: 10.5 per cent, non-potential diabetics with glucosuria: 3.7 per cent, potential diabetics without glucosuria: 3.4 per cent, and in the control group (non-potential diabetics without glucosuria): 0.3 per cent. A positive correlation was found between the level of fasting plasma glucose (FPG) early in pregnancy, and the result of OGTT later in pregnancy. When FPG exceeded 89 mg/100 ml (75 mg/100 ml whole blood) the incidence of diabetic curves increased significantly. By combining the following criteria: potential diabetics – glucosuria – fasting plasma glucose, FPG, it was found that the percentage of pregnant women, which ought to be investigated with an OGTT, could be reduced to 4 per cent, while the sensitivity and the specificity of the screening was 78 per cent and 89 per cent, respectively. This approach also resulted in the detection of all the most treatmentrequiring cases of diabetes. The practical use of the screening method is described.

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Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes

Acta Endocrinologica ◽

10.1530/eje.0.1470243 ◽

2002 ◽

pp. 243-248 ◽

Cited By ~ 49

Author(s):

L Kalabay ◽

K Cseh ◽

A Pajor ◽

E Baranyi ◽

GM Csakany ◽

...

Keyword(s):

Insulin Resistance ◽

Gestational Diabetes ◽

Pregnant Women ◽

Normal Pregnancy ◽

Tnf Alpha ◽

Control Group ◽

Anthropometric Parameters ◽

Necrosis Factor Alpha ◽

C Peptide ◽

Glucose Ratio

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

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Assessment of the optimal cutoff value of fasting plasma glucose to establish diagnosis of gestational diabetes mellitus in Chinese women

Scientific Reports ◽

10.1038/s41598-019-52509-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Bing Yan ◽

Ya-xin Yu ◽

Yin-ling Chen ◽

Wei-juan Su ◽

Yin-xiang Huang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Chinese Women ◽

Optimal Cutoff ◽

Cutoff Value ◽

Fasting Plasma

Abstract Our aim is to assess the optimal cutoff value of fasting plasma glucose (FPG) in Chinese women at 24–28 weeks’ gestation by performing oral glucose tolerance test (OGTT) to improve diagnostic rate of gestational diabetes mellitus (GDM). Data were derived from the Medical Birth Registry of Xiamen. A FPG cutoff value of 5.1 mmol/L confirmed the diagnosis of GDM in 4,794 (6.10%) pregnant women. However, a FPG cutoff value of 4.5 mmol/L should rule out the diagnosis of GDM in 35,932 (45.73%) pregnant women. If we use this cutoff value, the diagnosis of GDM to about 27.3% of pregnant women will be missed. Additionally, a 75-g OGTT was performed in pregnant women with FPG values between 4.5 and 5.1 mmol/L, avoiding the performance of formal 75-g OGTT in about 50.37% pregnant women. Meanwhile, according to maternal age and pre-pregnancy BMI categories, with FPG values between 4.5 mmol/L and 5.1 mmol/L, which had high sensitivity, to improve the diagnostic rate of GDM in all groups. Further researches are needed to present stronger evidences for the screening value of FPG in establishing the diagnosis of GDM in pregnant women.

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Performance and the Optimal Cut-Off Value of First-Trimester Fasting Plasma Glucose To Identify Gestational Diabetes Mellitus: A Retrospective Study From Southern China

10.21203/rs.3.rs-1067857/v1 ◽

2021 ◽

Author(s):

Jia-Ning Tong ◽

Lin-Lin Wu ◽

Yi-Xuan Chen ◽

Xiao-Nian Guan ◽

Kan Liu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Retrospective Study ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Maternal Age ◽

First Trimester ◽

Fasting Plasma

Abstract Purpose Previous studies have suggested that first-trimester fasting plasma glucose (FPG) is associated with gestational diabetes mellitus (GDM) and is a predictor of GDM. The aim of the present study was to explore whether first-trimester FPG levels can be used as a screening and diagnostic test for GDM in pregnant women. Methods This retrospective study included pregnant women who had their first-trimester FPG recorded at 9-13+6 weeks and underwent screening for GDM using the 2-hour 75 g oral glucose tolerance test (OGTT) between 24th and 28th gestational weeks. The cut-off values were calculated using a receiver operating characteristic (ROC) curve. Results The medical records of 28,030 pregnant women were analysed, and 4,669 (16.66%) of them were diagnosed with GDM. The mean first-trimester FPG was 4.62 ± 0.37 mmol/L. The total trend in the optimal cut-off value of first-trimester FPG in pregnant women was 4.735 mmol/L, with a sensitivity of 49%, a specificity of 67.6% and AUC of 0.608 (95% CI: 0.598-0.617, p༜0.001). Moreover, as the maternal age increased, the optimal cut-off values increased, respectively. The results suggest that first-trimester FPG can be considered a marker for identifying pregnant women with GDM. Conclusion The level of first-trimester FPG increased slightly with maternal age and, as maternal age increased, the optimal cut-off values increased, especially after age 30. The first-trimester FPG should be considered a screening marker when diagnosing GDM in pregnant women.

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The role of serum fasting plasma glucose in gestational diabetes screening

Perinatal Journal ◽

10.2399/prn.20.0281003 ◽

2020 ◽

Vol 28 (1) ◽

pp. 11-16

Author(s):

İlknur Çöl Madendağ ◽

Mefkure Eraslan Şahin ◽

Yusuf Madendağ

Keyword(s):

Gestational Diabetes ◽

Pregnant Women ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Threshold Value ◽

Tolerance Test ◽

Oral Glucose ◽

Fasting Plasma ◽

Specificity And Sensitivity ◽

Tertiary Center

Objective We aimed to investigate the performance of fasting plasma glucose (FPG) level, checked between 24 and 28 weeks of gestation, for the diagnosis of gestational diabetes mellitus (GDM) in order to find out whether FPG level would help to identify potential GDM cases or not in pregnancies which do or do not undergo oral glucose tolerance test (OGTT). Methods This study was performed retrospectively in a tertiary center by accessing the records of 2950 patients who underwent 75-g OGTT in between 24 and 28 weeks of gestation. GDM diagnosis was established according to the one-step screening test results. In the patients diagnosed with GDM, the most successful threshold value for the diagnosis calculated statistically was determined for FPG. The specificity and sensitivity values were calculated for FPG. Results After applying the exclusion criteria, 1736 of 2043 pregnant women were normal and 307 (15%) of them were diagnosed with GDM. The mean age was higher in the pregnant women with GDM than the healthy pregnant women when they were compared according to the demographic characteristics (28.6±4.3 vs. 26.2±4.1, p<0.001). Body mass index was also higher in the pregnant women with GDM compared to the health pregnant women (26±2.1 vs. 24±3.1 kg/m2, p<0.001). Other characteristics were similar in both groups. ROC analysis was performed for FPG and the most significant threshold value was found 88 mg/dL (p<0.001, area under curve 0.876, 95% confidence interval 0.850–0.903). Conclusion When FPG is >88 mg/dl in pregnant women who do not want to undergo OGTT, they should be informed in detail about both OGTT and GDM and its potential complications. Thus, the number of GDM cases without diagnosis and its potential complications would decrease.

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High Fasting Plasma Glucose during Early Pregnancy: A Review about Early Gestational Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2017/8921712 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 20

Author(s):

E. Cosson ◽

L. Carbillon ◽

P. Valensi

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Early Pregnancy ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Hypoglycemic Agents ◽

Early Management ◽

Fasting Plasma

Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing.

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Effect of Carbohydrate-Restricted Dietary Pattern on Insulin Treatment Rate, Lipid Metabolism and Nutritional Status in Pregnant Women with Gestational Diabetes in Beijing, China

Nutrients ◽

10.3390/nu14020359 ◽

2022 ◽

Vol 14 (2) ◽

pp. 359

Author(s):

Mingxuan Cui ◽

Xuening Li ◽

Chen Yang ◽

Linlin Wang ◽

Lulu Lu ◽

...

Keyword(s):

Lipid Metabolism ◽

Gestational Diabetes ◽

Nutritional Status ◽

Insulin Therapy ◽

Pregnant Women ◽

Early Pregnancy ◽

Insulin Treatment ◽

Blood Glucose Control ◽

Control Group ◽

Significant Difference

Carbohydrates play an important role in blood glucose control in pregnant women with GDM. Carbohydrate-restricted dietary (CRD) pattern for gestational diabetes mellitus (GDM) has been widely used in clinics, but the change in insulin utilization rate beyond CRD intervention in GDM remains unclear. The aim of the present study was to explore the application of insulin in pregnancy with GDM, as well as the influence of CRD pattern on lipid metabolism and nutritional state. A retrospective study of 265 women with GDM who delivered in Peking University People’s Hospital from July 2018 to January 2020 was conducted using a questionnaire survey. Women were divided into a CRD group or a control group according to whether they had received CRD intervention during pregnancy. There was no statistically significant difference in the rate of insulin therapy between the two groups (p > 0.05), the initial gestational week of the CRD group combined with insulin treatment was significantly higher than that of the control group (p < 0.05), and the risk of insulin therapy was positively correlated with fasting plasma glucose (FPG) in early pregnancy (p < 0.05). The incidence of abnormal low-density lipoprotein cholesterol levels in the CRD group was significantly lower than that in the control group (p < 0.05). There were no significant differences in nutritional indexes between the two groups. The results indicate that CRD intervention may be effective in delaying the use of insulin and improving the blood lipids metabolism during GDM pregnancy, while nutritional status may not be significantly affected under CRD intervention, and a high FPG in early pregnancy with GDM may be a risk factor for combined insulin therapy with CRD intervention.

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Association between maternal triglycerides and disturbed glucose metabolism in pregnancy

Acta Diabetologica ◽

10.1007/s00592-020-01644-z ◽

2021 ◽

Author(s):

Daniel Eppel ◽

Michael Feichtinger ◽

Tina Lindner ◽

Grammata Kotzaeridi ◽

Ingo Rosicky ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Pregnant Women ◽

Early Pregnancy ◽

Early Gestation ◽

Glucose Levels ◽

Increased Risk ◽

Mean Glucose ◽

In Pregnancy

Abstract Aims Dyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy. Methods Sixty-seven pregnant women received a detailed metabolic characterization at 12+0–22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0–27+6 weeks of gestation. Results Elevated triglycerides in early gestation were associated with insulin resistance and β-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03–1.34, p=0.022 for an increase of 10 mg/dl). Conclusions Hypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and β-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.

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Changes of Serum Adiponectin and Glycated Albumin Levels in Gestational Diabetes Mellitus Patients and Their Relationship with Insulin Resistance

Iranian Journal of Public Health ◽

10.18502/ijph.v49i7.3578 ◽

2020 ◽

Author(s):

Qingju WANG ◽

Juan DU ◽

Fenglian LIU

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Glycated Albumin ◽

Serum Adiponectin ◽

Control Group ◽

Childbearing Age ◽

And Control

Background: We aimed to investigate the changes of serum adiponectin and glycated albumin (GA) levels in gestational diabetes mellitus patients and their relationship with insulin resistance. Methods: Overall, 137 pregnant women were enrolled from Jinan City People's Hospital, Laiwu District, China from Jan 2015 to Jun 2018. Among them, 71 pregnant women with gestational diabetes mellitus were examined as diabetes group, and 66 normal pregnant women as normal pregnant women group. In addition, 58 normal non-pregnant women of childbearing age who were examined in our hospital during the same period were selected as a control group. The serum adiponectin and GA levels of the three groups were compared, and the relationship between serum adiponectin, GA levels and insulin resistance was analyzed. Results: The serum adiponectin level of pregnant women in gestational diabetes mellitus (GDM) group was significantly lower than that of normal pregnant women and control group (P=0.031, P=0.027). The serum GA level of pregnant women in GDM group was significantly higher than that of normal pregnant women and control group (P<0.001). Pearson correlation analysis showed that GA was positively correlated with Fasting plasma glucose (FPG), Fasting insulin (FINS) and Insulin resistance index(HOMA-IR) levels (P<0.001), while adiponectin was negatively correlated with FPG FINS and HOMA-IR levels (P<0.001). Conclusion: Abnormal levels of serum GA and adiponectin are closely related to insulin resistance in patients with gestational diabetes mellitus. Detection of serum GA and adiponectin levels can diagnose gestational diabetes mellitus quickly and effectively.

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