Diabetes and pregnancy study (DAPSY): a 10-year single-center cohort study of pregnancies affected by diabetes.

PURPOSE: The aim of our study was to investigate to what degree clinical characteristics can contribute to incidence and structure of pregnancy and childbirth complications in women with diabetes, and to reveal key risk factors for adverse outcomes. METHODS: We conducted a retrospective single-center cohort study from January 2008 through December 2017, including 3069 singleton pregnancies, affected by type 1 diabetes (T1D, n = 498), type 2 diabetes (T2D, n = 214), and gestational diabetes mellitus (GDM, n = 2357). RESULTS: More than 10 years duration of T1D associated with increased risk for preterm birth (RR 2.03, 95% CI 1.28-3.20) and preeclampsia (RR 1.57, 95% CI 1.09-2.26). Diabetic nephropathy, same as diabetic proliferative retinopathy, was associated with increased risk of C-section, preeclampsia development, SGA delivery. In patients with T1D who received CSII (12%), we do not report superior outcomes compared to MDI. Pre-pregnancy HbA1c level less than 6.5% reduced the risk of preeclampsia for T1D (RR 0.28, 95% CI 0.19-0.67) and risk of LGA birth for T2D (RR 0.43, 95% CI 0.19-0.92). Achieving glycemic target values by full-term pregnancy reduced the risk of excessive fetal adiposity (RR 0.81 for T1D, RR 0.39 for T2D). For T2D and GDM, the leading risk factors were obesity and chronic hypertension. For patients with GDM, insulin administration and early diagnosis of GDM were the significant risk factors for adverse outcomes. CONCLUSION: Diabetes during pregnancy is challenging for the clinician, but optimizing glycemic control, treatment regimens, and close attention to comorbidities can help to reduce the risks and ensure appropriate quality diabetes management.

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.

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.

Time and mode of delivery in diabetic pregnancy: a review.

The review presents some renewed data on the problem of optimal time and modes of delivery for women with various types of diabetes mellitus (DM 1 and 2, gestational diabetes). The necessity of making the universal delivery strategy algorithm for women with DM comes out of adverse outcomes high frequency, where the main cases are fetal macrosomia, fetal shoulder dystocia and perinatal mortality. Despite significant interest for this issue, there is still no common delivery tactics in the world for pregnant women with carbohydrate metabolism disorders. The main obstacle is evidence-based tests and meta-analysis insufficiency. So far, further studies are necessary to obtain high quality data concerning optimal terms and modes of delivery for women with DM.

Maternal insulin-like growth factors and insulin-like growth factor-binding proteins for macrosomia prediction in diabetic and nondiabetic pregnancy: A prospective study.

OBJECTIVE: Attributable to the insulin-like growth factor (IGF) axis involvement in fetal growth regulation, possible contribution of the maternal IGF axis to antenatal fetal macrosomia diagnosis is a subject of particular interest in diabetic pregnancy. METHODS: A total of 130 women were prospectively enrolled in a longitudinal single-center cohort study. The four study groups were: type 1 diabetes (n = 40), type 2 diabetes (n = 35), gestational diabetes (n = 40), and control (n = 15). IGF-1 and IGF-2 and insulin-like growth factor-binding protein (IGFBP) 1, 3, 6, and 7 serum levels were analyzed in 11- to 14-week and 30- to 34-week samples with a specific immunoassay. RESULTS: In mothers of large-for-gestational-age neonates (90th percentile), higher (median test) first-trimester IGF-1 (P = 0.007) and lower IGFBP-1 (P = 0.035) were observed. The IGF-1/IGFBP-1 ratio was positively associated with neonatal weight (r = 0.434, P < 0.001). Receiver operating characteristic analysis revealed an association between large for gestational age and the first-trimester IGF-1 (area under the curve [AUC] = 0.747, P < 0.001), IGFBP-1 (AUC = 0.334, P = 0.011), and IGF-1/IGFBP-1 ratio (AUC = 0.750, P < 0.001). IGF-1/IGFBP-1 ratio had better performance for prediction of birth weight over 4000 g (AUC = 0.822, P < 0.001). CONCLUSION: The authors detected different first-trimester IGF-1 and IGF-1/IGFBP-1 thresholds applicable for either supposition or rejection of macrosomia diagnosis. Further investigation is needed to determine how the maternal IGF axis can contribute to fetal macrosomia prediction.

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.

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.

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.