Gestational Diabetes Mellitus In Patients Research Articles

Gestational diabetes mellitus in patients undergoing assisted reproductive techniques or conceiving spontaneously: an analysis on maternal and foetal outcomes.

With the rise of medically assisted reproductive techniques (ART) the number of pregnanciescomplicated by gestational diabetes mellitus (GDM) has increased. The aim of this study was to evaluateretrospectively the outcomes of pregnancies complicated by GDM who conceive trough ART (cases) compared tothose who conceived spontaneously (controls). In 670 women with GDM, 229 cases and 441 controls, followed by the Diabetology of Padua, between2010-2022, clinical-metabolic maternal characteristics and maternal-foetal outcomes were evaluated. As for the maternal clinical-metabolic characteristics, plasma glucose levels at 60' and 120' under oralglucose tolerance test (OGTT) at time of diagnosis were significantly higher in cases (177.4 ± 31.1 vs 170.9 ± 34.1 mg/dl, p = 0.016; 151.5 ± 32.2 vs 144.0 ± 33.4 mg/dl, p = 0.005 respectively). Furthermore, at diagnosis, cases showhigher levels of total cholesterol (257 ± 53 mg/dl vs 246 ± 52 mg/dl; p = 0.012) and triglycerides (199.8 ± 83.2 mg/dl vs 184.9 ± 71.3 mg/dl; p = 0.02) compared to controls. As for maternal outcomes, thyroid disfunction, was recorded in ahigher percentage in case (21.4% vs 14.3%; p = 0.008), as well as, the frequency of cesarean section (50.3% vs41.2%; p = 0.038) and twin pregnancies (16.2% vs 2.5%; p < 0.001). As for neonatal outcomes, there were nostatistically significant differences, except for the birth weight of the second twin, which was significantly lower incases (2268 ± 536 vs 2822 ± 297 g; p = 0.002). No other significant differences were found. This study showed no meaningful differences in the outcomes of GDM pregnancies who were conceived with ART compared to that arose spontaneously as the patients were promptly diagnosed and treated.

Молекулярно-генетические предикторы перинатальных осложнений гестационного сахарного диабета у беременных после применения вспомогательных репродуктивных технологий

Aim: to assess the impact of carrying polymorphisms of genes related to lipid and carbohydrate metabolism, vascular tone, and angiogenesis on the complications development related to gestational diabetes mellitus (GDM) in patients with pregnancies resulting from the use of assisted reproductive technology (ART). Patients and Methods: a comprehensive cohort study was conducted. The main group (n=123), comprised of pregnant patients after the use of ART with GDM, was divided into 2 subgroups: 1A — pregnant women with perinatal complications (n=76); 1B — pregnant women without perinatal complications (n=47). The comparison group (n=105) included patients with pregnancies resulting from ART, without GDM. The perinatal complications analyzed in the study included preeclampsia, placental insufficiency, fetal growth retardation, and small for gestational age. Molecular genetic testing was conducted using allele-specific real-time PCR. Polymorphisms of the PPARG (Pro12Ala C&gt;G), TCF7L2 (IVS3 C&gt;T), ApoB Pro2739leu G&gt;A, VEGF-A: -634 G&gt;C, eNOS Glu298Asp G894T G&gt;T genes were studied. Results: carrying the polymorphic Pro12Pro allele of the PPARG gene (Pro12Ala &gt;G) was associated with an increased risk of developing GDM in patients after ART (odds ratio (OR) 2.451, 95% confidence interval (CI) 1.60–3.746, p=0.001). Conversely, the AlaP12Ala allele of the PPARG gene has a protective effect against these risks (OR 0.408, 95% CI 0.267–0.623, p=0.001). It was noted that carrying the TCF7L2 IVS3 TT genotype was associated with an increased risk of developing GDM in patients after ART (OR 3.795, 95% CI 1.482–9.720, p=0.004). Carrying the CC genotype of the VEGF-A -634 G&gt;C gene (OR 3.607, 95% CI 1.084–5.218, p&lt;0.05), as well as the recessive homozygous TT genotype of the eNOS 894 G&gt;T gene (OR 2.637, 95% CI 1.033–6.374; p&lt;0.05), was associated with an increased risk of developing perinatal complications of GDM in patients after ART. Conclusion: identifying genetic determinants of GDM associated with perinatal complications is important for determining the high-risk group at the stage of ART preparation and early pregnancy. Early identification of high-risk patients will allow for effective preventive measures before entry into the program, and for objective analysis of the clinical signs concerning the disease progression, as well as timely correction of carbohydrate metabolism disorders to improve perinatal outcomes. KEYWORDS: ART, gestational diabetes, perinatal complications, gene polymorphisms related to lipid and carbohydrate metabolism, gene polymorphisms — angiogenesis and vascular tone regulators. FOR CITATION: Melkozerova O.A., Murzin A.V., Tretyakova T.B., Deryabina E.G. Molecular-genetic predictors concerning the perinatal complications of gestational diabetes mellitus in pregnant women after assisted reproductive technologies. Russian Journal of Woman and Child Health. 2024;7(1):4–11 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-1.

Association of ABO and RH Blood Groups with Gestational Diabetes Mellitus in Patients Attending a Tertiary Care Hospital of Lahore, Pakistan

Objective: To find out any association of ABO and Rh blood groups with gestational diabetes mellitus (GDM). Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology and Gynecology departments of Combined Military Hospital-Lahore from Jun to Sep 2020. Methodology: A total of 250 patients of GDM and 250 pregnant ladies with normal glucose tolerance (NGT) were included in the study. The Oral glucose tolerance test (OGTT) was performed with a 75g glucose load, and results were interpreted according to the American Diabetes Association 2020 criteria. Blood glucose samples were taken in sodium fluoride containers in fasting conditions, 1 hour and 2 hours post-glucose load. Samples for blood groups were obtained in plain and EDTA containers. Blood glucose samples were analyzed using the Hexokinase method's automated chemistry analyzer, Cobas c-501. ABO and RhD blood grouping were carried out by forward and reverse techniques in the blood bank of CMH Lahore. Results: A total of 250 (50%) pregnant ladies with OGTT suggestive of Gestational Diabetes Mellitus and 250 (50%) pregnant ladies with OGTT suggestive of Normal Glucose Tolerance (NGT) were included in the study. No statistically significant difference was observed with ABO and RhD blood groups among them (p=0.944). Conclusion: There is no significant association found between ABO and RhD blood groups with Gestational Diabetes Mellitus.

Letrozole-stimulated endometrial preparation protocol is a superior alternative to hormone replacement treatment for frozen embryo transfer in women with polycystic ovary syndrome, a cohort study

BackgroundThe current routine endometrial preparation protocol for women with polycystic ovary syndrome (PCOS) is hormone replacement treatment (HRT). Letrozole is rarely used in frozen embryo cycles. Evidence confirming whether letrozole-stimulated (LS) protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable remains lacking.MethodsThis was a retrospective cohort study involving all frozen embryo transfer cycles with LS and HRT for PCOS during the period from Jan 2019 to December 2020 at a tertiary care center. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between LS and HRT protocols after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which LS protocol was suitable.ResultsThe results of multivariate logistic regression showed that LS was significantly associated with a higher clinical pregnancy rate (70.9% vs. 64.4%;aOR:1.41, 95%CI: 1.18,1.68), live birth rate (60.5% vs. 51.4% aOR:1.49, 95%CI: 1.27,1.76), and a lower risk of miscarriage (14.7% vs. 20.1% aOR: 0.68, 95%CI: 0.53,0.89), hypertensive disorders of pregnancy (6.7% vs. 8.9% aOR: 0.63, 95%CI: 0.42,0.95), and gestational diabetes mellitus (16.7% vs. 20.7% aOR:0.71, 95%CI: 0.53,0.93) than HRT. There were no significant differences in other outcomes such as preterm birth, cesarean delivery, small for gestational age, or large for gestational age between the two endometrial preparation protocols. Subgroup analysis showed that LS had higher live birth rates than HRT in most of the subgroups; in the three subgroups of maternal age ≥ 35 years, menstrual cycle < 35 days, and no insulin resistance, the live birth rates of the two endometrial preparation protocols were comparable.ConclusionsLS protocol could improve the live birth rate and reduce the incidence of miscarriage, hypertensive disorders of pregnancy and gestational diabetes mellitus in patients with PCOS. LS protocol is suitable for all types of patients with PCOS. LS should be considered the preferred endometrial preparation protocol for women with PCOS.

P-612 Comparison the effectiveness and safety of letrozole-stimulated and hormone replacement treatment in endometrial preparation for frozen embryo transfer in patients with polycystic ovary syndrome

Abstract Study question Whether letrozole-stimulated protocol has advantages over hormone replacement therapy (HRT) in frozen embryo transfer in patients with polycystic ovary syndrome (PCOS)? Summary answer Letrozole-stimulated protocol is more suitable for endometrial preparation than HRT in patients with PCOS, which can increase the live birth rate and reduce pregnancy complications. What is known already The current routine endometrial preparation protocol for women with PCOS is HRT. However, HRT is expensive, and recent studies have found HRT may increase the risk of adverse maternal and neonatal complications such as hypertensive disorders of pregnancy. Letrozole induces mono-ovulatory and has no antiestrogenic effect, and has been found to increase live birth rate compared with clomiphene in fresh embryo cycles. However, Letrozole is rarely used in frozen embryo cycles. Whether letrozole-stimulated protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable is still lack of evidence. Study design, size, duration This is a retrospective cohort study involving all frozen embryo transfer cycles with letrozole-stimulated and HRT for PCOS during the period from August 2018 to December 2020 at a tertiary care center. Participants/materials, setting, methods A total of 2011 letrozole-stimulated cycles and 2211 HRT cycles were included in the analysis. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between letrozole-stimulated protocol and HRT after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which letrozole-stimulated protocol was suitable. Main results and the role of chance After adjusting for confounding, letrozole-stimulated protocol increased the clinical pregnancy rate (OR,1.44; 95%CI,1.21-1.70), live birth rate (OR,1.49; 95%CI,1.27-1.74) and reduced the incidence of miscarriage (OR, 0.71; 95%CI,0.55-0.92), hypertensive disorders of pregnancy (OR, 0.66; 95%CI,0.45,0.98), gestational diabetes mellitus (OR,0.75; 95%CI,0.57,0.98) and cesarean section (OR,0.78; 95%CI,0.61,0.99) than HRT. There were no significant differences in other outcomes such as preterm birth, small for gestational age, and large for gestational age between the two endometrial preparation protocols. Subgroup analysis according to maternal age, BMI, insulin resistance and PCOS classification showed that the live birth rate of letrozole-stimulated protocol was significantly higher than that of HRT in all subgroups. Limitations, reasons for caution This study is a retrospective study, the population characteristics of the two endometrial preparation protocols existed differences. Although multivariate logistic regression was used to adjust some factors, the interference of known and unknown factors on the outcomes cannot be completely avoided. Wider implications of the findings This retrospective study found letrozole-stimulated protocol has more advantages than HRT, which can improve the live birth rate and reduce the incidence of hypertensive disorders of pregnancy, gestational diabetes mellitus in patients with PCOS. High-quality well-powered randomised clinical trials and possible mechanistic studies are needed to further validate this conclusion. Trial registration number NA

Interactive effects of gestational diabetes mellitus and maximum level of total bile acid in maternal serum on adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy

ObjectiveTo study the combined effect of gestational diabetes mellitus (GDM) and maximum level of maternal serum total bile acid (TBA) on the incidence of adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy (ICP).MethodsThis was an observational study with 724 women with ICP. Perinatal outcomes were compared by the presence of GDM. Logistic regression was used to assess the independent and multiplicative interactions of GDM and maximum maternal serum TBA on adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Andersson to calculate relative excess risks.ResultsThe incidence of GDM in patients with ICP was 21.55%. Maternal age, pre-pregnancy weight, parity, and gravidity were positively correlated with GDM. Hypertensive disorders of pregnancy (HDP) and fetal distress rates were higher in the GDM vs. non-GDM group. There were no significant differences in biochemical outcomes (i.e., Triglyceride (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA)) between the two groups. In terms of adverse pregnancy outcomes, GDM was only associated with maximum TBA concentration for cesarean section. No additive or pairwise interactions were detected between GDM and maximum TBA concentration and HDP, PPH, preterm delivery, LGA, SGA, and cesarean section.ConclusionGDM independently contributes to adverse pregnancy outcomes among women with ICP. However, the combined effects of GDM and maximum TBA concentration on adverse pregnancy outcomes do not appear to be multiplicative or additive.

Obstetric and perinatal pathology in pregnant women who had complications from the group of the Great Obstetrical Syndromes

The objective: to analyze the obstetric and perinatal outcomes of childbirth in pregnant women who had complications from the group of the great obstetrical syndromes.Materials and methods. A retrospective statistical analysis of obstetric and perinatal outcomes of childbirth of 239 pregnant women (the Ist group – main one) who had complications from the group of the great obstetrical syndromes (GOS). They were divided into three subgroups: Ia subgroup included 103 pregnant women with severe preeclampsia (PE), Ib subgroup – 67 pregnant women with placental insufficiency, with clinical manifestation of fetal intrauterine growth retardation (IUGR), Ic subgroup – 69 pregnant women with spontaneous preterm birth in the gestational age 22-36 weeks. The control group (CG) included 56 practically healthy pregnant women with a normal reproductive history and uncomplicated course of this pregnancy.Statistical processing of the study results was performed using standard programs Microsoft Excel 5.0 and Statistica 6.0.Results. The incidence of gestational diabetes mellitus in patients of the I group (28 (11.7 %) women) was higher than in CG (2 (3.6 %) persons). Cervical insufficiency was diagnosed in every fifth patient of Ic subgroup (12 (17.3 %) patients; χ2=15.56, p&lt;0.01; OR=9.25; CI 95%: 2.55–33.54 relative to CG), gestational anemia – in 179 (74.8 %) pregnant women in the I group and 18 (32.1 %) women in CG (p&lt;0.01).A significantly high rate of mild congenital malformations was present in subgroup Ib (7 (10.4 %) of pregnant women; χ2=12.67, p&lt;0.01; OR=7.93; CI 95%: 2.14-29.26). 21 patients in the I group had with antenatal fetal death, 6 (5.8 %) – severe PE, 11 (16.4 %) – IUGR. Five cases of early neonatal mortality was diagnosed in the I group. The rate of perinatal mortality in the I group was high and amounted to 108.7 ‰.The operative delivery in the I group was performed in 127 (53.1 %) patients which is significantly more than in CG (χ2=42.93, p&lt;0.01; OR=4.93; CI 95%: 2.99– 8.13). In 24 (18.9 %) pregnant women in the I group the indication for operative delivery was acute distress, which is significantly more than in CG (2 (3.6 %) women; χ2=7.36, p&lt;0.01; OR=5.17; CI 95%: 1.2–22.28). The mean score on the Apgar scale in newborns in CG was significantly higher compared with the I group (p&lt;0.01).Conclusions. The course of pregnancy and childbirth in women who had complications from the group of the great obstetrical syndromes was accompanied by the development of gestational diabetes, gestational anemia and cervical insufficiency. Complications such as fetal distress, severe preeclampsia, fetal growth retardation with decompensated hemodynamic disorders of the uterine and placental blood circulation, led to a high frequency of cesarean section in these patients.

Diabetes mellitus and periodontal disease

Diabetes mellitus (DM) is a chronic non-transmittable disease and, alongside periodontal disease, another chronic disease, but with infectious and inflammatory etiology, that have increasing prevalence. The link between the two comorbidities is bidirectional, with common aspects such the inflammatory state, altered immune response and healing process. This link is alimented, also, by oxidative stress, an element that can initiate proinflammatory pathways in both pathologies. Moreover, periodontal disease favors the development of DM complications by a multifactorial mechanism centered on hyperglycemia, that leads to damage of the endothelial vascular cells, characteristic for microvascular complications, while the periodontal bacteria and their waste products, and inflammatory cytokines lead to an increase in systemic inflammation and damage of the vascular walls that aggravates the atherogenic process. The increase of novel cases of type 2 DM or gestational DM in patients with periodontitis has no sufficient data. Dental caries is favored by DM and not by periodontal disease. So, DM is a well-known risk factor for periodontal disease and, on the other hand, periodontitis influences the metabolic control and favors the development of DM complications, but with a link between these conditions that is not fully understood. Other comorbidities, such as missing teeth, depression, osteoporosis are, also, positively associated to higher risk of development for periodontal disease. Patients with DM should be regularly screened for periodontal disease and referred to therapy if necessary, while the patients with periodontal disease should be screened for the presence of DM.

Metformin monotherapy is an effective alternative for management of gestational diabetes mellitus in patients refusing insulin monotherapy

A clinical decision report using: Ghomian N, Vahed SHM, Firouz S, Yaghoubi MA, Mohebbi M, Sahebkar A. The efficacy of metformin compared with insulin in regulating blood glucose levels during gestational diabetes mellitus: A randomized clinical trial. J Cell Physiol. 2019;234(4):4695-4701. https://doi.org/10.1002/jcp.27238 for a patient with gestational diabetes mellitus (GDM) who does not wish to undergo insulin monotherapy.

The risk factors of gestational diabetes mellitus in patients with polycystic ovary syndrome: What should we care.

The influencing factors of gestational diabetes mellitus (GDM) in the polycystic ovary syndrome (PCOS) patients remain unclear, we aimed to investigate the risk factors of GDM in patients with PCOS, to provide reliable evidence for the prevention and treatment of GDM in PCOS patients.PCOS patients treated in our hospital from January 1, 2019 to October 31, 2020 were included. The personal and clinical treatment details of GDM and no GDM patients were analyzed. Logistic regressions were performed to analyze the factors influencing the occurrence of GDM.A total of 196 PCOS patients were included, the incidence of GDM in patients with PCOS was 23.98%. There were significant differences in the age, body mass index, insulin resistance index, fasting insulin, testosterone, androstenedione, and sex hormone-binding protein between GDM and no GDM patients with PCOS (all P < .05), and no significant differences in the family history of GDM, the history of adverse pregnancy, and multiple pregnancies were found (all P > .05). Age ≥30 years (odds ratio (OR) 2.418, 95% confidence interval (CI) 1.181–3.784), body mass index ≥24 kg/m2 (OR 1.973, 95%CI 1.266–3.121), insulin resistance index ≥22.69 (OR 2.491, 95%CI 1.193–4.043), fasting insulin ≥22.71 mIU/L (OR 2.508, 95%CI 1.166–5.057), testosterone ≥2.85 nmol/L (OR 1.821, 95%CI 1.104–2.762), androstenedione ≥6.63 nmol/L (OR 1.954, 95%CI 1.262–2.844), sex hormone-binding protein <64.22 nmol/L (OR 1.497, 95%CI 1.028–2.016) were the independent risk factors of GDM in patients with PCOS (all P < .05). The incidence of preeclampsia, premature delivery, premature rupture of membranes, polyhydramnios, and postpartum hemorrhage in the GDM group was significantly higher than that of the no-GDM group (all P < .05). There was no significant difference in the incidence of oligohydramnios between the 2 groups (P = .057).The incidence of GDM in PCOS patients is high, and the measures targeted at the risk factors are needed to reduce the occurrence of GDM in patients with PCOS.

Does intracytoplasmic sperm injection increase the risk of gestational diabetes in patients with polycystic over?

Aim: Some studies found that in vitro fertilization (IVF) pregnancies were correlated with an increase in the incidence of gestational diabetes mellitus (GDM). The purpose of this study was to determine the effect of Intracytoplasmic Sperm Injection (ICSI) on the risk of GDM in patients with polycystic over syndrome (PCOS). Material and Methods: This retrospective study was conducted on 862 women below 40 who applied to gynecology and obstetrics clinic between January 2015 and May 2020. Their BMI was close to each other. They all had a single fetus, and they did not have a diabetes history. The individuals who participated in the study were tested based on 75 g OGTT (oral glucose tolerance test). Demographical characteristics, biochemical findings, and treatment styles were evaluated. Those with GDM history in the previous pregnancy were excluded from the study. Results: The mean age and BMI of the patients and the differences observed in the control and case groups were not statistically significant (p&amp;gt;0,05). Preparandial (p=0,000), 1st-hour blood glucose levels of OGTT (p=0,000), and 2nd-hour blood glucose levels of OGTT (p=0,000) of the case group were statistically higher than those in the control group (p&amp;lt;0,05). Conclusion: The confirmation of the indicators which increase the risk of GDM development with PCOS and follow-up in the early pregnancy period might minimize maternal and fetal complications depending on GDM. This study is significant since it investigates the effect of ICSI in patients with PCOS, spontaneous, and IVF pregnancies.

Dyslipidemia in Pregnancy and the Proper Reference Values: A Retrospective Study in South China

Background: Dyslipidemia during pregnancy is associatied with the risk of adverse pregnancy outcomes. However, there is no uniform diagnostic criteria. “Williams Obstetrics 24th Edition” (WO24) and Wang et al gave different lipid references based on ethnic groups. To address the proper reference values of pregnant lipid, we conducted this retrospective study in pregnant women in South China. Methods: 642 pregnant women were calculated the normal lipid range by 95th percentile and analyzed the association between lipid levels and adverse pregnancy outcomes by logistic regression models. Prevalence of adverse pregnancy outcomes in dyslipidemia patients diagnosed by the three different references were compared by Pearson’s chi-squared (χ2) test. Results: The prevalence of dyslipidemia were 15.26% by the references of our research, 11.53% by WO24, and 17.45% by Wang, respectively. TC level was the risk factor of preterm birth (PTB); and TG level was associated with the risk of gestational diabetes mellitus (GDM) and PTB. The odds radio (OR) for GDM in patients with abnormal TG levels were 4.28[1.28-14.28] by WO24’s, 3.06[1.43-6.57] by ours, and 2.62[1.13-6.11] by Wang's. The OR for PTB in patients with abnormal TG levels were 4.22[1.21-14.69] by WO24’s, 3.04[1.22-7.62] by Wang’s, and 2.31 [0.95-5.63] by ours. A increased risk of macrosomia was only seen in patients with abnormal TC level by Wang's reference (OR 3.67 [1.12-12.06]). Conclusions: Dyslipidemia during pregnancy is associated with the increases of pregnant complications. The reference by Wang et al were more applicable in Southern China.

Association between thyroid function and risk of gestational diabetes mellitus in assisted pregnancies: A retrospective cohort study

AimsTo explore the association between thyroid function and gestational diabetes mellitus (GDM) risk in assisted pregnancies. MethodsWe screened 57,386 pregnant women treated from February 2013 to October 2017, and 2211 patients were retrospectively enrolled, and their data were analyzed based on quintile groups constituted based on serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels. Odds ratios (ORs) of GDM were analyzed by multivariate logistic regression, adjusted for maternal age and pre-pregnancy body mass index (BMI). ResultsThe prevalence rate of GDM was 20.1%. Lower FT4 levels were associated with an increased risk of GDM (ORQ2 = 1.512, 95% confidence interval [CI] 1.073–2.132, p = 0.018; ORQ1 = 1.620, 95% CI 1.161–2.261, p = 0.005), but this association disappeared after adjustments. TPOAb+ titer was associated with an increased risk of GDM (aOR = 1.472, 95% CI 1.068–2.028, p = 0.018). Higher TSH (aORQ5 = 2.882, 95% CI 1.919–6.975, p = 0.019) or lower FT4 (aORQ1 = 3.156, 95% CI 1.088–9.115, p = 0.034) levels were associated with an increased risk of GDM in assisted pregnancies for TPOAb+ patients. ConclusionTPOAb+ is an independent risk factor for GDM in patients with assisted pregnancies. Higher TSH or lower FT4 levels, with TPOAb+ detection, are risk factors for GDM in assisted pregnancies.

Do raised two-hour pre-pregnancy insulin levels confer the same risks of developing GDM, as raised fasting levels, in recurrent miscarriage patients?

This study questioned whether raised pre-pregnancy two-hour (2 h) insulin levels, measured in recurrent embryonic miscarriage (RM) patients via a 75 g Oral Glucose Tolerance Test (OGTT), are associated with an increased risk of gestational diabetes mellitus (GDM) in a subsequent pregnancy. Patients had a 75 g OGTT and insulin levels evaluated (n = 170). 54.1% had normal glucose and insulin levels, 45.9% had levels indicating hyperinsulinism (HI). In the 98 patients who achieved a pregnancy, the prevalence of GDM was 3.7% in those without HI, and 35.7% in the patients who only had raised 2 h insulin levels. While HI has been described as a risk factor for miscarriages only in relation to raised fasting (basal) insulin levels, this study demonstrated that raised 2 h insulin levels predict an increased risk of GDM in a subsequent pregnancy. Thus raised 2 h insulin levels likely confer a similar risk to raised fasting insulin levels in RM patients.Impact statementWhat is already known on this subject? Fasting hyperinsulinism is known to be associated with an increased risk of gestational diabetes mellitus (GDM) in pregnancy. Hyperinsulinism, as reflected by the fasting (basal) insulin levels >20mU/L, has been recognized as a risk factor for recurrent miscarriages, particularly in patients with polycystic ovarian syndrome (PCOS), in the World literature. Raised two-hour insulin levels have not been considered as a risk factor in the literature before.What do the results of the study add? We have demonstrated a 10-fold increase in the development of GDM in patients with fasting insulin resistance, and/or raised 2h insulin levels, and an almost 10-fold increase in patients with only raised 2h levels. 58.8% of the patients who subsequently developed GDM only had raised 2h levels and would have been missed with routine testing.What are the implications of these findings for clinical practice and/or further research? Our study has demonstrated that GDM was three times more prevalent in the patients with only raised 2h levels, than in those only with raised fasting levels, reflecting insulin resistance/hyperinsulinism. Insulin studies including 2h insulin levels are therefore an important factor to consider when working up these patients. Insulin studies pre-pregnancy may be useful in identifying women at risk of suffering miscarriages or of developing GDM in a subsequent pregnancy.

Risk of developing gestational diabetes in women after assisted reproductive technologies

Hypothesis/aims of study. Gestational diabetes mellitus (GDM) is one of the leading causes of perinatal morbidity and mortality. The use of assisted reproductive technologies (ART) is an independent risk factor for the development of GDM. Among other risk factors are overweight, diabetes burdened heredity, previous GDM, previous birth weight more than 4 kgs, stillbirth, miscarriage in history, glucosuria, polyhydramnios in this pregnancy, age over 30 years, polycystic ovary syndrome. The most significant risk factor for GDM is excess weight before pregnancy. The aim of this study was to investigate the risks of GDM in patients after ART.&#x0D; Study design, materials, and methods. 342 case histories of women with single pregnancy for the period 2014–2017 were studied on archival material. The main group consisted of 234 women with single pregnancy after ART. The comparison group comprised 108 medical records of fertile women with a history of single pregnancy that occurred spontaneously. The exclusion criteria in the comparison group were pregestational diabetes mellitus and severe extragenital pathology.&#x0D; Results. The incidence of GDM was significantly higher in the group of women in whom pregnancy occurred after ART compared to the comparison group (15.4 ± 0.4% and 5.5 ± 0.4% respectively). In the main group, patients were more likely to have overweight, extragenital pathology and pregnancy complications.&#x0D; Conclusion. The increase in the frequency of GDM among patients after ART is probably associated with late reproductive age, initially negative somatic background at the time of entry into the IVF protocols, as well as long-term hormone therapy during pregnancies after ART, starting from early terms.

The Effect of Metformin Therapy for Preventing Gestational Diabetes Mellitus in Women with Polycystic Ovary Syndrome: A Meta-Analysis.

This study was to analyze the efficacy of metformin intervention in preventing gestational diabetes mellitus (GDM). A systematic review and meta-analysis of clinical trials or observational studies of metformin intervention in preventing symptoms of GDM during pregnancy were performed. Medline, Embase, and Cochrane Library were searched through to now. The main evaluated primary outcomes were incident of GDM, miscarriage, preterm delivery, and neonatal mortality. The evaluated secondary outcomes were mean difference of gestational age at birth and birth weight between metformin group and control group. We included 6 studies including 3 randomized clinical trials (RCTs), 2 observational studies, and 1 non-RCT in our meta-analysis. A total of 643 patients were enrolled for a follow-up study with continued metformin therapy (n=341) or not (n=302) during pregnancy. Metformin therapy reduced the proportion of patients developing GDM (log Odds Ratio: -1.27; 95%CI: -2.24 to -0.30) but had no significant effect on reducing the proportion of abortion, preterm delivery, and neonatal death in pregnant women with polycystic ovary syndrome (PCOS). Also, it did not cause a significant difference in gestational age at birth and birth weight in metformin group versus control/placebo group. Metformin was associated with less frequent GDM development than control diets, suggesting that it is the appropriate intervention to be prescribed to prevent GDM in patients with PCOS.

Preventive and Therapeutic Role of Dietary Inositol Supplementation in Periconceptional Period and During Pregnancy: A Summary of Evidences and Future Applications.

Although inositol dietary deficiency in the general population has not been demonstrated at the serum level, several findings are emerging regarding the impact of inositol supplementation in periconceptional period and in early phases of pregnancy. We are aimed to summarize all experimental (murine in vivo and in vitro murine embryo studies) and clinical (human) evidences regarding the role of inositol in the prevention and treatment of folate-resistant embryo neural tube defects (FR-NTDs) and gestational diabetes mellitus (GDM). We also collected all information regarding the effect that inositol supplementation may have in the metabolic reassessment of early and late pregnancy in order to draw evidence-based conclusions and suggest further studies defining the potential therapeutic role of this molecule in human reproduction. The systematic review of literature clearly showed that inositol supplementation in preconceptional period and in early phase of pregnancy reduces the risk of developing GDM in patients at increased risk. Furthermore, continued intake during pregnancy improves the metabolic status of affected patients, but further studies are needed to confirm this end point. All women at risk of FR-NTDs assuming inositol from the periconceptional period until late pregnancy are reported to have healthy newborns without any significant complications linked to inositol supplementation.

Early Diagnosis of Gestational Diabetes Mellitus in Patients With Elevated Body Mass Index [300

INTRODUCTION: Increased body mass index (BMI, calculated as weight (kg)/[height (m)]2) in a pregnant patient can put her at risk of gestational diabetes mellitus (GDM) by altering her insulin resistance early in pregnancy. The objective of this study was to determine a one-step test for GDM as early as 16 weeks of gestation in patients with increased BMI, thus minimizing fetal and maternal complications. METHODS: Between February 2008 and February 2012, 200 pregnant patients with BMI greater than 25 were registered for this prospective double-blind randomized study. Group A received 50 g glucola and group B received 100 g at 16 weeks of gestation. Patients who had impaired glucose tolerance (130–139 mg) received counseling about exercise and diet and those who had abnormal glucola (greater than 140 mg) also received a consult with perinatologists. Student's t test, χ2 test, and statistical analyses were run using SPSS 21. RESULTS: A total of 176 patients completed (A=89, B=87) glucola at 16 weeks of gestation. Impaired glucose tolerance was noted in 11 patients (A=6.7%, B=5.7%). Abnormal glucose tolerance was noted in 37 patients (A=12.3%, B=29.8%). Additionally 30 new cases of impaired glucose tolerance were diagnosed at 28 weeks of gestation with 50 g glucose (A=12.2%, B=4.4%). The data demonstrated that there was no statistically significant difference in weight gain, hemoglobin, hematocrit, platelet, blood pressure, mode of delivery or fetal weight between patient groups who had abnormal glucose screening test and received counseling and those who had normal glucose screening. CONCLUSION: This study showed that diagnosing impaired glucose tolerance in early pregnancy in patients with elevated BMI and providing them counseling helped to prevent GDM complications. A one-step test using a 100-g glucola test in early pregnancy in patients with elevated BMI is promising.

Impaired proliferation of pancreatic beta cells, by reduced placental growth factor in pre-eclampsia, as a cause for gestational diabetes mellitus.

Reduced increase in serum placental growth factor (PLGF) levels frequently occurs in patients with pre-eclampsia (PE) and thus has been used as a predictive factor for developing PE. However, it has remained elusive how shortage of PLGF could affect pancreatic endocrine homoeostasis and function in pregnancy to lead to development of gestational diabetes mellitus (GDM). We used l-NAME injection in mice, as a model of human PE, in which PLGF levels were significantly reduced. We not only confirmed reduced serum PLGF levels in patients with PE but also detected strong correlation of serum PLGF levels and presence of GDM. We found that growth of beta cell mass during pregnancy was significantly impaired by l-NAME injection, as a result of reduced beta cell proliferation. This may explain the higher risk of developing GDM in patients with PE. Moreover, provision of exogenous PLGF in l-NAME-treated pregnant mice significantly rescued beta cell proliferation, with subsequent increase in beta cell mass, suggesting that shortage in PLGF may be responsible for impaired beta cell growth and higher occurrence of GDM in patients with PE. Our study highlighted a pivotal role for PLGF in prevention and treatment of GDM in patients with PE.

Risk of gestational diabetes mellitus in patients undergoing assisted reproductive techniques

ObjectiveTo compare the incidence of gestational diabetes mellitus (GDM) between pregnancies conceived spontaneously and pregnancies conceived following assisted reproductive technology (ART). Study designThis cross-sectional study evaluated the medical records of 215 women who conceived spontaneously and 145 women who conceived following ART from September 2011 to October 2012. Exclusion criteria were: polycystic ovary syndrome, maternal age ≥40 years, family history of diabetes in first-degree relatives, pre-pregnancy diabetes, glucose intolerance treated with hypoglycaemic agent (e.g. metformin), history of GDM, history of stillbirth, recurrent miscarriage, history of baby with birth weight ≥4kg (macrosomia), parity >3, Cushing syndrome, congenital adrenal hyperplasia and hypothyroidism. For better comparison of the incidence of GDM, the ART group was further subdivided into: (i) an in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) group (n=95); and (ii) an intrauterine insemination (IUI) group (n=50). The diagnosis of GDM was based on the criteria of the American Diabetes Association. ResultsThe incidence of GDM was significantly higher in the IVF/ICSI and IUI groups (43% and 26%, respectively) compared with the spontaneous pregnancy group (10%). Age, pre-pregnancy body mass index (BMI) and weight gain in pregnancy were similar among women with GDM in all three groups. In addition, the incidence of pregnancy-induced hypertension was significantly higher in the IVF/ICSI group (21%) compared with the spontaneous pregnancy group (7%). Logistic regression analysis demonstrated four strong risk factors for GDM: age, BMI, mode of ART and progesterone use during pregnancy. ConclusionThis study indicated that the risk of GDM is two-fold higher in women with singleton pregnancies conceived following ART compared with women who conceived spontaneously. In addition, progesterone use during pregnancy was found to be an important risk factor for GDM. This subject requires further study.