RESUMO
OBJECTIVE: To examine the associations of in utero exposure to maternal diabetes with surrogate measures of offspring pubertal timing (age at peak height velocity [APHV]) and speed of pubertal growth (peak height velocity [PHV]). STUDY DESIGN: Data from 77 exposed and 340 unexposed youth followed from age 2 to 19 years (51% non-Hispanic white, 50% female) were analyzed using the Exploring Perinatal Outcomes among Children study, a historical prospective cohort. Maternal diabetes status was collected from obstetric records, and child heights from 2 years to current age from pediatric records. Other covariates were collected during research visits. The superimposition by translation and rotation method, using height measurements (4-52 per participant), modeled APHV and PHV. Accelerated failure time analyses were used to test whether exposure to maternal diabetes was associated with younger APHV and faster PHV. RESULTS: Adjusting for child's sex, race/ethnicity, and socioeconomic status, median APHV was reached ~3 months earlier in youth exposed to maternal diabetes compared with unexposed youth (P < .03). Youth exposed to maternal diabetes had a faster PHV than unexposed youth: exposed girls had 10.5% greater median PHV compared with unexposed girls and exposed boys had a 4.0% greater median PHV compared with unexposed boys (P < .001 for exposure by sex interaction). CONCLUSIONS: Our findings provide evidence that exposure to maternal diabetes in utero is associated with earlier pubertal timing and faster pubertal growth. Whether earlier puberty or faster speed of pubertal growth mediates the association between maternal diabetes exposure and later chronic disease risk remains to be studied.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Gestacional/fisiopatologia , Gravidez em Diabéticas/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Puberdade Precoce/etiologia , Adolescente , Antropometria , Estatura , Índice de Massa Corporal , Criança , Pré-Escolar , Colorado/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Masculino , Menarca , Gravidez , Estudos Prospectivos , Puberdade , Maturidade Sexual , Classe Social , Adulto JovemRESUMO
AIMS: The objective of this study was to assess the mechanisms underlying pancreatic islet adaptation in diabetic mothers and their pups. Additionally, the influence of pancreatic adaptations on maternal reproductive performance was also investigated. MAIN METHODS: Wistar rats were injected with streptozotocin for diabetes induction. At adulthood (3â¯months), all animals underwent an oral glucose tolerance test (OGTT) for glucose assessment as an inclusion criterion. Following, the animals were mated. At day 18 of pregnancy, the mothers were killed for blood collect ion to determine fasting insulin and glucagon concentrations. The pancreas was removed and processed for the immunohistochemical analysis of insulin, glucagon, somatostatin, Ki-67 and PDX-1, superoxide dismutase 1 (SOD-1), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). The pregnant uterus was also collected for the evaluation of embryofetal loss. KEY FINDINGS: The diabetic rats showed increased glucose, serum glucagon and insulin concentrations, and embryofetal loss rates. They also showed a reduction in pancreatic islets area and percentage of cells stained for insulin, increased the percentage of non-ß cells (alpha e delta cells) stained for Ki-67, glucagon, and somatostatin. Moreover, the cells stained for somatostatin were spread across the islets and showed stronger staining for MDA and weaker staining for GSH-Px. SIGNIFICANCE: Diabetes leads to adaptive responses from the endocrine pancreas in pregnancy that especially involves non-ß cells, modifying the mantle-core structure. Nonetheless, these adaptations are not enough for glucose homeostasis and affect the maternal environment, which in turn impairs fetal development.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Gravidez em Diabéticas/fisiopatologia , Animais , Antioxidantes/metabolismo , Enzimas/metabolismo , Feminino , Teste de Tolerância a Glucose , Insulina/sangue , Masculino , Estresse Oxidativo , Hormônios Pancreáticos/metabolismo , Gravidez , Ratos WistarRESUMO
BACKGROUND: Fetal impairment caused by a deleterious intrauterine environment may have long-term consequences, such as oxidative stress and genetic damage. Rats born as small-for-gestational-age (SPA) were submitted to exercise (swimming) before and during pregnancy. The animals exhibited glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight, showing the benefit of exercise for these rats. We hypothesised that regular exercise in SPA during gestation could prevent DNA damage in these animals and in their offspring, contributing to altered fetal programming of metabolism in the offspring. Severe diabetes was induced by streptozotocin treatment, to obtain SPA newborns. At adulthood, pregnant SPA rats were randomly distributed into two groups: exercised (SPAex - submitted to swimming program) or not-exercised (SPA - sedentary rats). Post-partum, blood was collected for analysis of DNA damage (comet assay) and oxidative stress. SPAex rats presented lower DNA damage levels, decreased lipid peroxidation, and a lower rate of newborns classified as large-for-pregnancy-age. DNA damage was also lower in SPAex newborns. We conclude that swimming applied to SPA pregnant rats contributes to decreased DNA damage and lipid peroxidation in the dams, and decreased DNA damage and macrosomia in their offspring.
Assuntos
Ensaio Cometa/métodos , Dano ao DNA , Feto/metabolismo , Mães , Condicionamento Físico Animal , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Natação , Fatores Etários , Animais , Animais Recém-Nascidos , Glicemia , Diabetes Mellitus Experimental/fisiopatologia , Feminino , Masculino , Estresse Oxidativo , Gravidez , Gravidez em Diabéticas/fisiopatologia , Ratos , Ratos WistarRESUMO
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.
Assuntos
Diabetes Mellitus Experimental/complicações , Reprodução , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Anormalidades Congênitas/etiologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/fisiopatologia , Implantação do Embrião , Feminino , Morte Fetal , Feto/metabolismo , Hemoglobinas Glicadas/metabolismo , Lipídeos/sangue , Tamanho da Ninhada de Vivíparos , Fígado/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Gravidez , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/fisiopatologia , Ratos Wistar , Fatores de TempoRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Gestacional/sangue , Hiperandrogenismo/complicações , Hiperinsulinismo/complicações , Resistência à Insulina , Gravidez em Diabéticas/sangue , Adulto , Androstenodiona/sangue , Chile , Sulfato de Desidroepiandrosterona/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Regulação para Baixo , Estradiol/sangue , Estriol/sangue , Estrona/sangue , Feminino , Humanos , Hiperandrogenismo/etiologia , Hiperinsulinismo/etiologia , Estudos Longitudinais , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Gravidez em Diabéticas/metabolismo , Gravidez em Diabéticas/fisiopatologia , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.
Assuntos
Animais , Masculino , Feminino , Gravidez , Ratos , Diabetes Mellitus Experimental/fisiopatologia , Gravidez em Diabéticas/fisiopatologia , Saco Vitelino/fisiopatologia , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Ciclo Celular/fisiologia , Proliferação de Células , Sobrevivência Celular , Peso Fetal , Ratos WistarRESUMO
The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Gravidez em Diabéticas/fisiopatologia , Saco Vitelino/fisiopatologia , Animais , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Ciclo Celular/fisiologia , Proliferação de Células , Sobrevivência Celular , Feminino , Peso Fetal , Masculino , Gravidez , Ratos , Ratos WistarRESUMO
BACKGROUND: Diabetic pregnancy have increased rates of congenital malformation and neonatal mortality. In vitro studies suggest hyperglycemia associated with diabetes impair embryogenesis but in vivo investigations on maternal hyperglycemic insult and early embryo development are scarce. We evaluated the embryofetal development on experimental diabetes models to assess whether hyperglycemia at preimplantation period impairs the progression of pregnancy. METHODS: Different hyperglycemic intensities were obtained by two experimental diabetes models. Female Sprague Dawley rats received streptozotocin at birth (mild diabetes) or at day 90 of life (severe diabetes). For both diabetic groups hyperglycemia was confirmed 5 days after diabetes induction and the mating was performed around 100 day of life. For preimplantation analysis, embryos were recovered at D4 of pregnancy. Another group of animals was submitted to laparotomy at D21 to assess contents of the uterus and fetal viability. RESULTS: Mild (i) and Severe (ii) diabetes modified the early development. Degenerating embryos percentage was higher compared to control (11%) (i) 30.7%, (ii) 37.3%. Cell number mean dropped according to hyperglycemic intensity (control 30.57, (i) 21.42, (ii) 13.42). Pre and post-implantation loss rates were higher in diabetic groups. The fetal viability also decreased from 96% in the control group to (i) 78.7% and (ii) 80.6%. CONCLUSION: Our results show that during diabetic pregnancy, preimplantation embryos present decreased cell number due to higher apoptosis rates, which are dependent of the hyperglycemic intensity. Moreover, fetal viability was also decreased suggesting that the quality of these embryos at long-term may be questioned.
Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Desenvolvimento Embrionário/fisiologia , Desenvolvimento Fetal/fisiologia , Gravidez em Diabéticas/fisiopatologia , Prenhez/fisiologia , Animais , Apoptose/fisiologia , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Feminino , Morte Fetal , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Estreptozocina/efeitos adversos , Fatores de TempoRESUMO
The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Diabetes Gestacional/fisiopatologia , Modelos Animais de Doenças , Gravidez em Diabéticas/fisiopatologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Feminino , Gravidez , Gravidez em Diabéticas/metabolismoRESUMO
Introducción: se conoce que en los últimos años, el manejo obstétrico ha enfatizado el control estricto de la glicemia en la madre y que ha mejorado la sobrevida fetal, la cual es directamente proporcional a la glicemia media materna. Objetivo: caracterizar los principales resultados en la experiencia hospitalaria sobre la vigilancia obstétrica y metabólica en la atención de gestantes diabéticas en el Hospital General Ciro Redondo García, Centro de Referencia Territorial en Artemisa. Métodos: se realizó un estudio observacional analítico, prospectivo y de corte longitudinal en el Hospital General Docente Ciro Redondo García de Artemisa desde junio de 2005 hasta junio de 2012. De un universo de 2 140 gestantes ingresadas, 240 fueron diagnosticadas diabéticas, constituyendo la muestra de estudio, Resultados: como diabéticas gestacionales (DG) se clasificó el 77,5 por ciento mientras que las diabéticas pregestacionales (DPG) constituyeron el 22,5 por ciento .Los grupos de edades de 31 a 36 años y de 20 a 25 años fueron los de mayor predominio en la diabetes gestacional pregestacional para un 29,1 por ciento y un 33,3 por ciento respectivamente. Los factores de riesgo de mayor predominio en el estudio fueron: la obesidad (44,2 por ciento ), la edad mayor de 34 años, polihidramnios, macrosomía previa y los abortos espontáneos (38,7; 18; 8,1; y 6,6 por ciento respectivamente). Otros factores de riesgo fueron los antecedentes familiares de diabetes mellitus de las gestantes, el diagnóstico de la diabetes gestacional después de las 20 semanas, la cesárea como el tipo de parto de mayor predominio y la edad gestacional a término al parto. Conclusiones: en un valorado sistema de salud pública como el cubano, se debe tomar medidas pertinentes para monitorear y controlar la morbilidad y complicaciones de las gestantes diabéticas
Background: it is known that, in recent years, obstetric management has made emphasis on the strict control of glycemia in the mother and the fetal survival has been improved, which is directly proportional to the mean maternal glycemia. Objective: to characterize the principal results in the hospital experience on obstetric and metabolic surveillance in the management of pregnant diabetic women in Ciro Redondo García General Hospital, Regional Reference Center in Artemisa. Methods: an observational analytical prospective cross-longitudinal study was conducted in Ciro Redondo García General Hospital in Artemisa from June 2005 to June 2012. From a universe of 2 140 pregnant women admitted in the hospital, 240 were diagnosed diabetics, representing them, the sample of the study. Results: the 77.5 percent of them were classified as gestational diabetic women (GD) whereas pregestational diabetic women (PGD) represented the 22.5 percent .The 31-36 and 20-25 age groups were the most predominant in gestational and pregestational diabetes, for a 29.1 percent and a 33.3 percent, respectively. The most predominant risk factors in the study were: obesity (44.2 percent ), age over 34 years, polyhydramnios, previous macrosomia, and spontaneous abortion (38.7, 18, 8.1, 6.6 percent respectively). Other risk factors were: family antecedents of diabetes mellitus in pregnant women, the time of diagnosis of gestational diabetes after the 20 weeks, the caesarean section as the most predominant type of delivery, and gestational age at delivery at term. Conclusions: in a valued Public Health System such as the Cuban one, appropriate measures should be taken to monitor and control morbidity and complications in pregnant diabetic women