Efficacy of automated insulin delivery in pregnant women with type 1 diabetes: a meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: Automated insulin delivery (AID) devices have shown to be a promising treatment to improve glycemic control in patients with type 1 diabetes mellitus (T1DM). However, its efficacy in pregnant women with T1DM remains uncertain. METHODS: PubMed, Scopus, Cochrane Central and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing AID to standard care (SC), defined as use of sensor-augmented pump and multiple daily insulin injections. Outcomes included time in range (TIR), nocturnal TIR, time in hypoglycemic and hyperglycemic ranges, among others. Sensitivity and trial sequential analyses (TSA) were performed. PROSPERO ID: CRD42023474398. RESULTS: We included five RCTs with a total of 236 pregnant women, of whom 117 (50.6%) received AID. There was a significant increase in nocturnal TIR (mean difference [MD] 12.69%; 95% CI 8.74-16.64; p < 0.01; I2 = 0%) and a decrease in glucose variability (standard deviation of glucose; MD -2.91; 95% CI -5.13 to -0.69; p = 0.01; I2 = 0%). No significant differences were observed for TIR, HBGI, LGBI, mean glucose and time spent in hyperglycemia and hypoglycemia. Regarding TSA, the statistical significance obtained in nocturnal TIR was conclusive and with minimal risk of a type I error. CONCLUSION: Our findings suggest that AID systems can significantly improve nocturnal glycemic control and potentially reduce glycemic variability in pregnant women with T1DM, with no effect in the risk of hypoglycemia and hyperglycemia compared with current insulin treatments.

Association between extrapolated time in range and large for gestational age infants in pregnant women with type 1 diabetes.

AIMS: To evaluate the association between extrapolated time in range (eTIR), measured by self-monitoring of blood glucose (SMBG), and large-for-gestational-age (LGA) infants in pregnancies with type 1 diabetes (T1D). METHODS: Retrospective cohort analysis including singleton pregnancies with T1D who started antenatal care before 20 gestational weeks and delivered live newborns at a Brazilian hospital between 2010 and 2019, with LGA fetuses as the main outcome. Glycemic records acquired using SMBG were categorized as eTIR, extrapolated time below range (eTBR), and extrapolated time above range (eTAR). Women were divided into two groups (LGA and adequate for gestational age [AGA]) and compared regarding clinical characteristics, obstetric outcomes, and frequencies of eTIR, eTBR, and eTAR. Logistic regression analysis verified the independent predictive variables for LGA infants. RESULTS: Data from 125 pregnancies were analyzed. For the first, second and third trimesters, each 1 % increase in eTIR was associated with a decreased risk of LGA by 2.9 % (OR: 0.971; 95%CI: 0.945-0.998), 2.5 % (OR: 0.975; 95%CI: 0.951-0.999) and 2.3 % (OR: 0.977; 95%CI: 0.955-0.998) and each 1 % increase in eTAR was associated with an increased risk of LGA by 2.7 % (OR: 1.027; 95%CI: 1.005-1.050), 3.9 % (OR: 1.039; 95%CI: 1.014-1.063) and 4.6 % (OR: 1.046; 95%CI: 1.018-1.075), respectively. CONCLUSION: The concept of TIR can be extrapolated to patients undergoing SMBG to assess the risk of LGA infants in pregnant women with T1D.

Experimental diabetes impairs maternal reproductive performance in pregnant Wistar rats and their offspring.

The aim of this study was to determine the effect of mild hyperglycemia on metabolism during pregnancy, the maternal reproductive performance, and the characteristics of the offspring in neonatal mild diabetic-induced Wistar rats. The experimental diabetes model was generated by neonatal streptozotocin administration (100 mg of streptozotocin/Kg bw/sc) in female Wistar rats. At adulthood, the control and diabetic group were mated. At the 20th day of gestation, a maternal and fetal blood sample were collected for biochemical measurement. The maternal livers, fetal livers, and placenta were removed for oxidative stress measurements. Maternal reproductive outcomes and fetal and placental morphometric measurements were analyzed. The fetuses were classified as small, appropriate, and large for pregnancy age, and examined for the presence of external anomalies. The diabetic group showed mild hyperglycemia, altered glucose tolerance, increased total cholesterol, triglycerides, and hemoglobin A1c during pregnancy. At the 20th day of gestation the diabetic mothers presented increased reabsorptions and embryonic losses before and after implantation, reduced corpora lutea number, litter size, implantation sites, live fetuses, and decreased efficiency of implantation rate. Similarly, the offspring showed reduced fetal, craniofacial, and placental dimensions, in addition to a higher proportion of small fetuses for pregnancy age. Mild hyperglycemia during pregnancy did not generate marked oxidative stress in the mother, and in fetal liver and placenta decreased antioxidant activity was evident by significant consumption of reduced glutathione. Mild diabetes led to a negative impact on maternal reproductive performance and characteristics of the offspring. This experimental model reproduced maternal and fetal outcomes of pregnant rats presenting controlled diabetes. ABBREVIATIONS: bw: body weight; sc: subcutaneous; DM: diabetes mellitus; STZ: streptozotocin; OGTT: oral glucose tolerance test; ITT: insulin tolerance test; GSH: glutathione; MDA: malondialdehyde; AOPPs: advanced oxidation protein products; TBARs: thiobarbituric acid reaction; SPA: small for pregancy age; APA: appropriate for pregnancy age; LPG: large for pregnancy age; ROS: reactive oxygen species.

Anti-Müllerian hormone in type 2 and gestational diabetes during the second half of pregnancy: relationship with sexual steroid levels and metabolic parameters.

Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during pregnancy. The effect of diabetes on anti-Müllerian hormone (AMH) levels during pregnancy is unclear. The aim of this study was to determine the AMH levels in women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to healthy (C) pregnant women during the second half of gestation. A prospective study of 69 pregnant women with T2D (N: 21), GD (N: 24) and C (N: 24) were followed up during the second half of pregnancy. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. AMH, sexual steroids, insulin, homeostatic model assessment of insulin resistance, HbA1c levels were measured. AMH levels were similar between T2D, GD and C (p = .07). A decline of AMH levels during the second half of gestation was observed in the three groups (p < .0001). AMH levels were negatively associated with age (p < .001). A positive association between AMH and testosterone (p < .05) was found in all groups. A progressive decline of AMH levels is observed in diabetic and healthy women during the second half of pregnancy. Testosterone levels are an independent factor that influences AMH levels during pregnancy. However, AMH levels are not affected by the presence of diabetes during gestation.

Maternal-Fetal Outcomes in 34 Pregnant Women with Type 1 Diabetes in Sensor-Augmented Insulin Pump Therapy.

BACKGROUND: Pregnancy in women with type 1 diabetes (T1D) is associated with increased risk of maternal complications and neonatal morbidity and mortality. Optimizing glycemic control improves these outcomes. OBJECTIVE: To describe the experience of using sensor-augmented insulin pump therapy (SAPT) and SAPT + low-glucose suspension (LGS) on pregnant women with T1D, including neonatal and maternal outcomes. METHODS: A prospective observational study was conducted in women with T1D who started SAPT and SAPT + LGS before or during pregnancy at the San Ignacio University Hospital Diabetes Center in Bogotá, Colombia. The main indication was severe hypoglycemia (SH) and poor glycemic control. Glycated hemoglobin (A1c), hypoglycemia, and maternal and fetal outcomes were assessed. RESULTS: Thirty-four pregnant women with T1D on SAPT and SAPT + LGS were included. Sixteen patients started therapy during pregnancy at a mean gestational age of 17.6 ± 8.3 weeks. Mean preconceptional A1c was 8.24% ± 2.02%. Absolute reduction of A1c level from prepregnancy to third trimester was -1.63% (P < 0.0001), with a significant clinical and statistical reduction in both groups, women who initiated SAPT before or during pregnancy. 52.9% of patients in second trimester and 66.6% in third trimester achieved A1c <6.5%, respectively. 91.1% underwent cesarean section. The main reasons were iterative cesarean (30%), fetal distress (20%), and preeclampsia (16%). The median gestational age at delivery was 37 weeks and 15 pregnancies resulted in preterm delivery. There was neither maternal-fetal mortality nor severe hypoglycemic episodes. Two patients had diabetic ketoacidosis. CONCLUSIONS: In pregnant patients with T1D and high risk of hypoglycemia, SAPT and SAPT + LGS should be considered as a therapeutic alternative for A1c reduction with a low risk of SH. However, additional studies are required to evaluate the efficacy and safety of this therapy during pregnancy.

Pregestational type 2 diabetes and gestational diabetes exhibit different sexual steroid profiles during pregnancy.

Higher androgen levels are observed in non-pregnant women with diabetes. Whether this hormonal profile is found during pregnancy is unknown. The aim of this study was to determine the sexual steroids levels in pregnant women with pregestational type 2 (T2D) and gestational diabetes (GD) compared to healthy control (C) pregnant women during the second half of pregnancy. A prospective study of 69 pregnant women with T2D (n = 21), GD (n = 24) and control (C, n = 24) was followed up during the second half of gestation. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. Androgens, sex hormone-binding globulin (SHBG), estrogens, estradiol/testosterone (E/T) ratio, insulin, glucose, HOMA-IR, were measured. Testosterone, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels were higher in T2D compared with C at each sampling point during pregnancy, even after adjusting for BMI and age. Estrogens levels and estradiol/testosterone ratio were lower in T2D and GD compared with C. Hyperandrogenemia, and higher insulin resistance is observed in T2D, but not in GD during pregnancy. Decreased estrogen and E/T ratio found in T2D and GD suggests a diminished aromatase activity during gestation. T2D and GD are associated with specific changes in sexual steroids and insulin resistance levels during pregnancy.

[Relationship between the level of maternal glycated hemoglobin and fetal hypertrophic cardiomyopathy]. / Relación entre el nivel de hemoglobina glucosilada materna y cardiomiopatía hipertrófica fetal.

BACKGROUND: Diabetes mellitus is a metabolic disorder commonly associated with pregnancy. It is shown that as the management of diabetes during pregnancy is optimized, decreases the frequency and severity of fetal and neonatal complications. The aim of this paper is to identify the relation between the level of maternal glycated hemoglobin and fetal hypertrophic cardiomyopathy. METHODS: An analitytic cross-sectional study was conducted. It included patients with single pregnancy of 28-37 weeks diagnosed with gestational or preconception diabetes mellitus. A fetal echocardiogram were performed, likewise measuring of glycated hemoglobin. RESULTS: 104 diabetic pregnant patients were included in the study, 83 patients in the group with normal glycated hemoglobin and 21 in the group with altered glycated hemoglobin. Of the 104 patients, 12 had fetal hypertrophic cardiomyopathy; 5 of the group with normal glycated hemoglobin and 7 with altered glycated hemoglobin. There is a clear association previously reported between the level maternal metabolic control and the presence of fetal and neonatal complications. CONCLUSIONS: A positive correlation between the values of high maternal glycated hemoglobin and increased thickness of the fetal ventricular septum was observed. Fetal echocardiographic assessment is recommended for all pregnant women with gestational and pre-pregnancy diabetes mellitus in order to early detection of fetal hypertrophic cardiomyopathy.

Introducción: la diabetes mellitus constituye la alteración metabólica más frecuentemente asociada al embarazo. A medida que se optimiza el manejo de la diabetes durante la gestación, disminuye la frecuencia y severidad de las complicaciones fetales y neonatales. El objetivo de este trabajo fue identificar la relación que existe entre el nivel de hemoglobina glucosilada materna y la cardiomiopatía hipertrófica fetal. Métodos: estudio transversal analítico de julio a noviembre del 2015. Se incluyeron pacientes con embarazo simple de las 28-37 semanas con diagnóstico de diabetes mellitus pregestacional o gestacional. Se les realizó un ecocardiograma fetal, asimismo se les efectuó la medición de hemoglobina glucosilada. Resultados: se incluyeron 104 pacientes embarazadas diabéticas en el estudio, 83 pacientes en el grupo con hemoglobina glucosilada normal y 21 con hemoglobina glucosilada alterada. De las 104 pacientes, 12 presentaron cardiomiopatía hipertrófica fetal; 5 del grupo con hemoglobina glucosilada normal y 7 del grupo con hemoglobina glucosilada alterada. Se identificó que existe una clara asociación reportada previamente entre el grado de descontrol metabólico materno y la presencia de complicaciones fetales y neonatales. Conclusiones: se observó una correlación positiva entre los valores de hemoglobina glucosilada materna elevada y el aumento del grosor del septum interventricular fetal. La evaluación ecocardiográfica fetal es recomendada en todas las embarazadas con diabetes mellitus gestacional y pregestacional.

Cetoacidosis diabética normoglicémica en el embarazo: caso clínico / Normoglycemic diabetic ketoacidosis in pregnancy: report of one case

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

May maternal lifestyle have an impact on neonatal glucose levels?

Neonatal glucose levels correlate negatively with umbilical cord levels of C-peptide, a polypeptide secreted with insulin. In other words, neonatal hypoglycemia results from excessive insulin secretion from fetal/neonatal beta cells. Given that insulin causes fat to be stored rather than to be used for energy, one would expect that chronic hyperinsulinemia would result in large-for-gestational-age neonates. The finding that many small-for-gestational-age neonates have hypoglycemia suggests that the stimulus for insulin production occurs close to delivery. We postulated that a potent stimulation of maternal insulin production close to delivery would also provide a potent stimulus for fetal and neonatal insulin production, causing neonatal hypoglycemia. This study has evaluated 155 mothers with markers of excessive insulin production (such as acanthosis or grade III obesity), or with situations characterized by increased insulin requirements (such as an invasive bacterial infection or use of systemic corticosteroid within a week before delivery; or sedentariness or high-carbohydrate intake within 24h before delivery) and their 158 neonates who were screened for glycemic levels at 1, 2 and 4h after birth. The minimum glucose level was correlated to the maternal parameters, and to classical predictors of neonatal hypoglycemia, such as low-birth weight and preterm delivery. The only independent predictors were sedentariness and high-carbohydrate intake within 24h before delivery. The risk of neonatal hypoglycemia increased five-fold with sedentariness, 11-fold with high-carbohydrate intake, and 329-fold with both risk factors. The risk of neonatal hypoglycemia seems to be highly influenced by maternal lifestyle within 24h before delivery. Controlled randomized trials may help determine whether a controlled carbohydrate diet combined with regular physical activity close to delivery can prevent neonatal hypoglycemia and all its severe complications to the newborn.

[Normoglycemic diabetic ketoacidosis in pregnancy: Report of one case]. / Cetoacidosis diabética normoglicémica en el embarazo: Caso clínico.

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

Depression and anxiety in pregnant women with diabetes or mild hyperglycemia.

INTRODUCTION: A number of physical and psychological changes that occur during pregnancy can stimulate the development of psychological disorders such as anxiety and depression. The study evaluated psychological aspects related to maternal depression and anxiety in pregnant women with diabetes mellitus or hyperglycemia, contrasting the results with those of non-diabetic pregnant women. METHOD: In a prospective and longitudinal approach, two questionnaires were applied and validated for use in Brazil, the Beck depression inventory and the State-Trait Anxiety Inventory. The questionnaires were applied to pregnant women at the first prenatal visit or at the time of disease diagnosis (T1) and reapplied at admission for delivery (T2). Regardless of the degree of hyperglycemia, both at first and in the second stage most women had severe anxiety trait. In early pregnancy (T1), however, severe state anxiety was more frequent in women with hyperglycemia than in those from the NG group. RESULTS: Most pregnant women showed moderate state anxiety over their pregnancy, regardless of glycemic status. In early pregnancy, however, severe state anxiety was more prevalent in hyperglycemic women than in those with normal glycemic status. Most women showed moderate trait anxiety and mild depression in both early and late pregnancy, irrespective of glycemic status. CONCLUSION: The incidence of severe state anxiety in early pregnancy is more frequent in women with diabetes or hyperglycemia, but their levels of trait anxiety and depression are not affected by glycemic status.

Preeclampsia in high risk women is characterized by risk group-specific abnormalities in serum biomarkers.

OBJECTIVE: To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor. STUDY DESIGN: We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index. RESULTS: 1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group. CONCLUSION: Patterns of serum biomarkers vary by high-risk group. These data support the hypothesis that multiple pathogenic pathways lead to the disease recognized clinically as preeclampsia.

Influence of treatment with quercetin on lipid parameters and oxidative stress of pregnant diabetic rats.

Among the numerous coadjuvant therapies that could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in clinical trials. We investigated the effect of quercetin on biochemical parameters in streptozotocin-induced (60 mg/kg body mass, by intraperitoneal injection) diabetic rats. A total of 32 female Wistar rats were distributed among 4 groups as follows: control (G1); control treated with quercetin (G2); diabetic (G3); and diabetic treated with quercetin (G4). Quercetin administered to pregnant diabetic rats controlled dyslipidemia and improved lipid profiles in diabetes mellitus, regulated oxidative stress by reducing the generation of lipid hydroperoxides, and increased the activity of the antioxidant enzyme glutathione peroxidase.

Diabetic rats exercised prior to and during pregnancy: maternal reproductive outcome, biochemical profile, and frequency of fetal anomalies.

The aim of this study was to evaluate the effects of exercise prior to or during pregnancy on maternal reproductive outcome, biochemical profile, and on fetal anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes. Wistar rats (minimum n = 11 animals/group) were randomly assigned the following groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4, sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic, exercised prior to and during pregnancy. A swimming program was utilized for moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain blood for biochemical measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups showed decreased fetal weights at term pregnancy, indicating slight intrauterine growth restriction (IUGR). In the diabetic dams, the swimming program did not have antihyperglycemic effects. The exercise applied only during pregnancy caused severe IUGR, as confirmed by reduced fetal weight mean, fetal weight classification, and ossification sites. Nevertheless, exercise was not a teratogenic factor and improved the rats' lipid profiles, demonstrating that the exercise presented possible benefits, but there are also risks prior and during pregnancy, especially in diabetic pregnant women.

Genotoxicity evaluation in severe or mild diabetic pregnancy in laboratory animals.

This study aimed to evaluate the genotoxicity (DNA damage levels) in lymphocyte samples from pregnant Wistar rats with severe or mild diabetes and in whole blood samples from their newborns. Wistar female rats (1 and 90 days of age) and male rats (approximately 90 days of age) were used. The experiment consisted of 2 experimental groups (n=8 animals/group): 1) rats with severe diabetes, 2) rats with mild diabetes. For mild diabetes induction, the rats received streptozotocin (STZ) subcutaneously (100 mg/kg body weight) at day of birth, and those showing glycemia from 120 to 300 mg/dL in their adult life were included. For induction of severe diabetes, adult rats received 40 mg/kg STZ (intravenous route), and those showing glycemia > 300 mg/dL were included. At day 21 of pregnancy, the rats were anesthetized and euthanized for removal of maternal and fetal blood samples for determination of the oxidative DNA damage by applying Endo III and Fpg using the comet assay. Thus, the rats with mild diabetes and their offspring showed higher Fpg-sensitive sites, reflecting the damage resulting from hyperglycemia. The rats with severe diabetes and their offspring showed higher oxidative DNA damage detected by Fpg and Endo III-sensitive sites, showing general repercussions related to diabetes. The enzymatic treatment for DNA damage evidenced that the maternal repercussions of diabetes are associated with oxidative DNA damage of their newborn, which was not reflected using only the analysis of DNA damage free of the enzymes.

[Effect of betamethasone in blood glucose levels in pregnant diabetic women at risk of preterm birth]. / Efecto de la betametasona en la glucemia de diabéticas embarazadas en riesgo de nacimiento pretérmino.

BACKGROUND: The bethametasone (BTM) induced hyperglycemia is not adequately known and managed in diabetic pregnant women. OBJECTIVE: To compare the betamethasone-induced hyperglycemia in pregnant women either healthy or with gestational or type 2 diabetes mellitus (diabetes mellitus). MATERIAL AND METHODS: Forty volunteer pregnant women at risk of premature rupture of membranes who received betamethasone (12 mg i.m. every 24 hours, 2 doses) were divided in four groups (10 women each): G1, healthy; G2, Diet treated diabetes mellitus; G3, Diet plus insulin treated diabetes mellitus; G4, type 2 diabetes mellitus treated with diet (n=6) or diet and insulin (n=4). Pre (p) and 2h-postprandial (pp) capillary blood glucose was measured throughout the day during 5 days of hospitalization. Student't test for independent and dependent samples was used. RESULTS: G1 had no significant changes in p or pp glucose. In G2 four women required de novo insulin administration while insulin dose was increased 39 to 112% and 26 to 64% in all women in G3 and G4, respectively to maintain p and pp glucose levels <95 mg/dL and < 120 mg/dL, respectively. The greatest changes occurred between days 2 to 4 after betamethasone. CONCLUSION: Betamethasone-induced hyperglycemia was greater in insulin treated women with gestational or type 2 diabetes and should not be administrated on an out-patient basis.

Effect of Morus nigra aqueous extract treatment on the maternal-fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus nigra, commonly known as black mulberry, is widely used in Brazilian folk medicine for the diabetes treatment. AIM OF THIS STUDY: To evaluate the effect of Morus nigra aqueous extract treatment on maternal lipid and oxidative stress profile, reproductive outcomes, and also fetal anomaly incidence from diabetic and non-diabetic rats. MATERIALS AND METHODS: Diabetes was induced by streptozotocin (40 mg/kg) in virgin female Wistar rats. Morus nigra leaf aqueous extract (400 mg/kg) was administered from day 0 to 20 of pregnancy. At day 21 of pregnancy, all rats were anesthetized and killed to obtain blood samples and maternal-fetal data. RESULTS AND CONCLUSION: After treatment with Morus nigra extract, non-diabetic and diabetic rats presented no glycemic changes. Fetuses from diabetic dams, regardless of Morus nigra treatment, were small for pregnancy age. In diabetic dams, plant treatment caused reduced MDA, cholesterol, triglycerides and VLDL levels, and decreased placental index and weight as compared to diabetic group. The fetuses from diabetic rats treated with Morus nigra extract had lower frequency of skeletal and visceral anomalies as compared to diabetic group. Thus, Morus nigra leaf aqueous extract failed to control hyperglycemia in diabetic rats. However, Morus nigra treatment had antioxidant effect, contributing to reduce incidence of internal anomalies in offspring from diabetic dams.

Maternal-fetal outcome, lipid profile and oxidative stress of diabetic rats neonatally exposed to streptozotocin.

BACKGROUND: There is no evidence about the integrated issue on glycemia, lipid profile, oxidative stress, and anomaly frequency of pregnant diabetic rats neonatally exposed to streptozotocin. OBJECTIVE: Evaluating the impact of hyperglycemia in diabetic rats neonatally exposed to streptozotocin on maternal reproductive and fetal outcomes and the relationship with lipid profile and maternal oxidative stress. MATERIAL AND METHODS: Ten 90-day-old female Wistar rats were mated to obtain offspring. Some of these newborns received streptozotocin (70 mg/kg, i. p. - n5-STZ group) and the remainder given only citrate buffer (control group) on their day 5 of life. At adult life, these rats (n=13 animals/group) were mated and, at day 21 of pregnancy, they were killed to obtain a maternal blood samples for biochemical determinations. The gravid uterus was weighed with its contents and fetuses were analyzed. RESULTS: At day 0 of pregnancy, glycemic means of n5-STZ rats were significantly greater compared to those of control rats, but presented fetuses classified as small for pregnancy age. The n5-STZ rats showed increased total cholesterol, triglycerides, MDA concentrations, lower SOD activity and increased frequency fetal visceral anomalies as compared to the control group. CONCLUSION: This study showed that the experimental model used led to mild hyperglycemia during pregnancy, although it did not lead to increased macrosomic fetus rates. The hyperglycemic maternal environment caused metabolic alterations, including increased triglyceride and total cholesterol concentrations, and elevated oxidative stress, contributing to increase fetal visceral anomalies.

Genotoxicity and fetal abnormality in streptozotocin-induced diabetic rats exposed to cigarette smoke prior to and during pregnancy.

BACKGROUND: Maternal hyperglycemia during early pregnancy is associated with increased risk of abnormalities in the offspring. Malformation rates among the offspring of diabetic mothers are 2-5-fold higher than that of the normal population, and congenital malformations are the major cause of mortality and morbidity in the offspring of diabetic mothers. Metabolic changes, such as hyperglycemia and the metabolites obtained from cigarettes both increase the production of reactive oxygen species (ROS) in the embryo or fetus, causing DNA damage. OBJECTIVE: To evaluate the maternal and fetal genotoxicity, and to assess the incidence of fetal anomaly in diabetic female rats exposed to cigarette smoke at different stages of pregnancy in rats. MATERIAL AND METHOD: Diabetes was induced by streptozotocin administration and cigarette smoke exposure was produced by a mechanical smoking device that generated mainstream smoke that was delivered into a chamber. Female Wistar rats were randomly assigned to: non-diabetic (ND) and diabetic (D) groups exposed to filtered air; a diabetic group exposed to cigarette smoke prior to and during pregnancy (DS) and a diabetic group only exposed to cigarette smoke prior to pregnancy (DSPP). On pregnancy day 21, blood samples were obtained for DNA damage analysis and fetuses were collected for congenital anomaly assessment. Statistical significance was set at p<0.05 for all analysis. RESULTS AND CONCLUSION: Exposure of diabetic rats to tobacco smoke prior to pregnancy increased fetal DNA damage, but failed to induce teratogenicity. Thus, these results reinforce the importance for women to avoid exposure to cigarette smoke long before they become pregnant.

Echocardiographic findings of congenital cardiopathies among fetuses of diabetic pregnant women and their relationship with plasma fructosamine levels.

OBJECTIVE: To study the occurrence of congenital cardiopathies at echocardiography (CCE) in fetuses whose mothers had preexisting diabetes mellitus (PGDM) and to study the potential of using fructosamine level as a late marker (beyond the first trimester) for CCE. METHODS: A register study covering 91 pregnant women that underwent routine fetal echocardiography ordered due to PGDM. The first dosage of plasma fructosamine found in 65 medical records was analyzed during prenatal care (20.4 ± 8.0 weeks of gestation). The presence or absence of structural or functional CCE was associated with fructosamine levels by logistic regression. We assessed the effect modification odds ratio by maternal age and insulin usage. RESULTS: Thirty-four fetuses (52.3% of 65 fetuses) presented CCE. Twenty of them had functional CCE and 14 presented structural CCE. The mean maternal plasma fructosamine level was higher among pregnant women whose fetuses presented CCE than in those whose fetuses did not (2.86 ± 0.73 mmol/l, 2.22 ± 0.54 mmol/l, respectively, p < 0.0001). Crude OR for CCE and abnormal plasma fructosamine (>2.68 mmol/l) was 9.6 (2.8-33.7, 95% CI, p < 0.0001). Adjusted OR by maternal age and insulin usage was 10.9 (2.7-45.2, 95% CI p < 0.0001). CONCLUSIONS: An abnormal plasma fructosamine level increases the chances of CCE occurring among referral pregnant women with PGDM.