Prediction of preeclampsia based on maternal serum endoglin level in women with pregestational diabetes mellitus.

PURPOSE: To evaluate the level of soluble endoglin (sEng) in pregnant women with pregestational diabetes mellitus (DM) and to assess its predictive value for preeclampsia development. METHODS: Ninety pregnant women were enrolled in the study forming five comparison groups: type 1 DM (not planned, n = 20; planned, n = 20), type 2 DM (diet, n = 15; insulin therapy, n = 20), and the control group (n = 15). The primary outcome was clinically confirmed preeclampsia. Maternal serum concentrations of sEng were measured at 11+0-13+6 and 30+0-33+6 weeks. RESULTS: sEng level was elevated in all patients with pregestational DM compared to the control group. Its plasma concentration increased with gestational age and in case of preeclampsia development. In patients with type 1 DM, serum sEng level did not depend on the presence of preeclampsia. This is evidence of severe metabolic disorder and endothelial dysfunction in these patients. The addition of sEng level to logistic models considering established risk factors (body mass index + age + HbA1c level) in the first and third trimesters significantly improved their performance for preeclampsia prediction. CONCLUSIONS: Eng level may become an important marker for early prediction of preeclampsia in women with pregestational DM.

Fetal growth regulation via insulin-like growth factor axis in normal and diabetic pregnancy.

OBJECTIVES: Diabetes mellitus (DM) in pregnancy and gestational diabetes remain a considerable cause of pregnancy complications, and fetal macrosomia is among them. Insulin, insulin-like growth factors (IGFs), and components of their signal-transduction axes belong to the predominant growth regulators and are implicated in glucose homeostasis. This study aimed to evaluate the available evidence on the association between the IGF axis and fetal anthropometric parameters in human diabetic pregnancy. METHODS: PubMed, Medline, Web of Science, and CNKI databases (1981-2021) were searched. RESULTS: Maternal and cord serum IGF-I levels are suggested to be positively associated with weight and length of neonates born to mothers with type 1 DM. The results concerning IGF-II and IGFBPs in type 1 DM or any of the IGF axis components in type 2 DM remain controversial. The alterations of maternal serum IGFs concentrations throughout diabetic and non-diabetic pregnancy do not appear to be the same. Maternal 1st trimester IGF-I level is positively associated with fetal birth weight in DM. CONCLUSIONS: Research on the IGF axis should take gestational age of sampling, presence of DM, and insulin administration into account. Maternal 1st trimester IGF-I level might become a predictor for macrosomia development in diabetic pregnancy.

Glucose variability as the risk factor of preeclampsia in pregnant patients with type 1 diabetes mellitus.

OBJECTIVE: To analyze glucose variability and investigate its role as a predictor for preeclampsia development in pregnant women with type 1 diabetes mellitus (T1DM) with various insulin therapy regimens. METHODS: A total of 200 pregnant women with T1DM were included in the study. A hundred women used continuous subcutaneous insulin infusion (CSII), and the rest of the group was administered with multiple daily insulin injections (MDI). Continuous glucose monitoring (CGM), index calculation of glucose variability (MAGE, MODD, CONGA, and CV), assessment of preeclampsia frequency and severity were conducted. RESULTS: The work results show the link between the severity rate of preeclampsia and the duration of T1DM as well as the level of HbA1c before and during pregnancy. The rate of preeclampsia in the group of women, using CSII comprises 26.8% of cases that appear less than in the group of those, administered with MDI that is 46.6% (χ2 = 5.45; р < .05). A negative correlation is defined between pathological glucose variability and gestational age when preeclampsia occurs. A negative correlation was also revealed between MODD, CV, and the time for the detection of preeclampsia: r = -0.30, r = -0.24, respectively. The study illustrates the correlation obtained between preeclampsia and glucose variability and the value of MAGE, MODD, CV, and SD. Preeclampsia development is affected by the duration of hyperglycemic conditions in the third trimester of pregnancy. The data in the group of women using MDI marks the early development of preeclampsia on the 33.0 [32-34] week of pregnancy compared to the group of women practicing CSII on 35.5 [33-36] week of pregnancy (Z = 5.4; p < .001). The increase of risk of preeclampsia development is proved in pregnant patients with T1DM when the hyperglycemic condition lasts more than 25% of a 24-h period according to the rate of CGM and measurements of glucose variability MODD > 1.07 and CONGA > 3.39. CONCLUSION: Comprehensive evaluation of the glycemic profile while using CGM revealed a correlation between pathological glucose variability and the frequency and severity of preeclampsia thus proving the benefits of CSII in pregnant patients with T1DM to perform glycemic targets and decrease glucose variability, which eventually led to the decrease of preeclampsia frequency in this group of women.

Are the first-trimester levels of PAPP-A and fb-hCG predictors for obstetrical complications in diabetic pregnancy?

OBJECTIVE: To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM). METHODS: It was a retrospective cohort study. Study groups were presented: type 1 DM (n = 100), type 2 DM (n = 50), and controls (n = 25). At 11 + 0 to 13 + 6 week's gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated. RESULTS: The study has shown that DM is associated with a high rate of perinatal complications: PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51-1.1), and type 2 DM-0.88 (IQR, 0.42-1.15) compared to the unaffected group 1.03 (IQR, 0.96-1.12; p = .025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p = .14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile: in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5-10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth. CONCLUSION: The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy.

Placental expression of endoglin, placental growth factor, leptin, and hypoxia-inducible factor-1 in diabetic pregnancy and pre-eclampsia.

OBJECTIVE: To evaluate a level of expression of endoglin (Eng), leptin (Lep), placental growth factor (PlGF), and hypoxia-inducible factor-1alpha (HIF-1α) in placenta among women with pre-eclampsia and diabetes mellitus (DM), considering the method of glycemia correction and preconception care. MATERIALS AND METHODS: A retrospective cohort study was conducted. A total of 124 women were divided into following groups: type 1 DM (n = 40), type 2DM (n = 31), gestational DM (n = 33), pre-eclampsia without DM (PE) (n = 10) and the control group (n = 10). The histochemical study was performed by using primary monoclonal antibodies to Eng, PlGF, Lep, and HIF-1α (Abcam, UK). RESULTS: The highest level of placental expression of Eng was observed in the PE group (20.34%). The same trend was also typical for T1DM (not planned) and insulin-treated groups: T2DM and GDM. An amount of cell with an PlGF expression was significantly higher in the control group (12.2%), while the lowest was observed in the pre-eclampsia group (1.18%) and T1DM (not planned) (1.26%). The placental leptin expression within each DM group was increased among the patients with unplanned pregnancy and those who received insulin therapy. We observed the lowest Lep expression in the PE group (6.3%). High level of HIF-1α expression was detected in T1DM (not planned) (30.44%) and PE (29.64%) as compared to the control group (11.62%). In T2DM and GDM insulin groups, the HIF-1α expression was significantly higher as compared to diet groups. CONCLUSION: The obtained data show that DM and pre-eclampsia are associated with changes in angiogenic and metabolic placental factor expressions. The degree of changes depends on preconception care and the control of glycemia level during pregnancy.

Maternal serum leptin, adiponectin, resistin and monocyte chemoattractant protein-1 levels in different types of diabetes mellitus.

OBJECTIVE: Evaluation of serum concentration of leptin, adiponectin, resistin, and MCP-1 in pregnant patients with different types of diabetes mellitus (DM) considering preconception planning and method of DM correction in 11-14th and 30-34th weeks of pregnancy. STUDY DESIGN: Longitudinal, prospective study included 130 pregnant women divided into the following comparison groups: type 1 DM (T1DM, n = 40), type 2 DM (T2DM, n = 35), GDM (n = 40), and the control group (n = 15). The ELISA method defined the levels of leptin, resistin, adiponectin, and MCP-1 concentration in serum, which was assessed in 11-14th and 30-34th weeks of pregnancy. Statistical analysis was accomplished using SPSS 23.0 and "Prism 8-GraphPad" software. RESULTS: The leptin level in the 1st trimester was the highest in T2DM insulin group compared to the control due to gestational age, hence in the 3rd trimester in all groups its serum concentrations appeared higher than in healthy patients (p = 0.0001). In the 1st trimester leptin levels directly correlated with women's BMI, newborns' weight and macrosomia rate, in the 3rd trimester - with OGTT levels, HbA1c, gestational hypertension, and preeclampsia rates. Resistin levels in the 1st and 3rd trimesters were increased in almost all DM groups compared to the control group (p = 0.0001). The study established direct positive correlation between resistin and HbA1c, birth weight, and preeclampsia. In the 1st trimester, adiponectin demonstrated the lowest levels in T2DM insulin compared to T1DM and the control group (p = 0.0001) while in the 3rd trimester, adiponectin levels declined alongside gestational age in DM patients and all the groups compared to the control group (p < 0.05). Adiponectin negatively correlated with BMI, OGTT levels, and preeclampsia rate. MCP-1 levels in T2DM appeared higher than in T1DM patients and the control group in the 1st trimester, whereas in the 3rd trimester MCP-1 declined, correlating with BMI, preeclampsia and OGTT levels. CONCLUSION: High rate of adverse perinatal outcomes in diabetic pregnancy might be developed due to more severe metabolic failures and further disturbances of adipokines expression.