Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study

Casson, Ian; Clarke, C. A.; Howard, Claire; McKendrick, O M; Pennycook, S; Pharoah, P O D; Platt, Mary Jane; Stanisstreet, Martin; Velszen, D van; Walkinshaw, Stephen

doi:10.1136/bmj.315.7103.275

Cited by 471 publications

(373 citation statements)

References 13 publications

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“…Future studies should make use of placental cell lines that might express adiponectin and adiponectin receptors endogenously to dissect further their signalling properties, including the dichotomy between the secretion and expression of adiponectin with IL-6 and leptin. With regard to GDM placentae compared with controls, future studies are needed to investigate not only the secretion of placental adiponectin and its regulation by cytokines in an explant system, but also any differences in p38 and ERK1/2MAPK that may exist, given the higher miscarriage rates in diabetic pregnancies [35,36]. Moreover, it will be interesting to investigate further what effect these cytokines have on adiponectin and its receptors in placentae, not only in GDM but also in those with type-1 diabetes mellitus, whose offspring are known to be at increased risk of developing obesity, impaired glucose tolerance and type 2 diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines

et al. 2006

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Aims/hypothesis: Pregnancy, a state of insulin resistance, is associated with elevated levels of cytokines and profound alterations in metabolism. Serum adiponectin, an adipokine with anti-inflammatory and insulinsensitising properties, has been shown to be lower in patients with gestational diabetes mellitus, a state of greater insulin resistance than normal pregnancies. Hypothesising that the human placenta is a source of adiponectin, we investigated its expression and secretion, and the regulation by cytokines of adiponectin and its receptors. Methods: Real-time RT-PCR, radioimmunoassay, Western blotting, radioligand binding and immunofluorescent analyses were applied to demonstrate the expression, secretion and functionality of placental adiponectin. Results: Adiponectin gene expression and protein were found in the human term placenta, with expression primarily in the syncytiotrophoblast. RIA of conditioned media from explant experiments revealed that the placenta can secrete adiponectin in vitro. Addition of conditioned media to HEK-293 cells transfected with the gene for adiponectin receptor-1 (ADIPOR1) altered the phosphorylation status of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase, an effect abolished after preabsorption with adiponectin antibody. Cytokines, including TNF-α, IFN-γ, IL-6 and leptin, differentially modulated placental adiponectin receptors as well as adiponectin gene expression and secretion. Interestingly, in placentae from women with gestational diabetes mellitus, we observed significant downregulation of adiponectin mRNA, significant upregulation of ADIPOR1 expression, and a non-significant increase in ADIPOR2 expression.Conclusions/ interpretation: Our results indicate that the human placenta produces and secretes adiponectin, and that adiponectin and its receptors are differentially regulated by cytokines and their expression altered in women with gestational diabetes mellitus. Collectively, our novel data suggest that adiponectin may play a role in adapting energy metabolism at the materno-fetal interface.

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Section: Discussionmentioning

confidence: 99%

Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines

et al. 2006

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“…The incidence of congenital malformation in type 1 diabetic pregnancy is estimated to be 4.2% to 9.4% compared with approximately 1% in the general population [1][2][3]. Although a planned pregnancy with optimal blood glucose control and folic acid supplements at the time of conception reduces the risk of congenital malformations, a recent prospective study showed that the incidence of congenital malformations is still elevated in women with type 1 diabetes [4].…”

Section: Introductionmentioning

confidence: 99%

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes

et al. 2009

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Aims/hypothesis Maternal diabetes during pregnancy increases the risk of congenital malformations such as neural tube defects (NTDs). Although the mechanism of this effect is uncertain, it is known that levels of nitric oxide synthase (NOS) and nitric oxide are elevated in embryos of a mouse model of diabetes. We postulated that overproduction of nitric oxide causes diabetes-induced congenital malformations and that inhibition of inducible NOS (iNOS) might prevent diabetic embryopathy. Methods Mice were rendered hyperglycaemic by intraperitoneal injection of streptozotocin. The incidence of congenital malformations including NTDs was evaluated on gestational day 18.5. We assessed the involvement of iNOS in diabetesinduced malformation by administering ONO-1714, a specific inhibitor of iNOS, to pregnant mice with streptozotocininduced diabetic mice and by screening mice with iNOS deficiency due to genetic knockout (iNos −/− ). Results ONO-1714 markedly reduced the incidence of congenital anomalies, including NTDs, in fetuses of a mouse model of diabetes. It also prevented apoptosis in the head region of fetuses, indicating that iNOS is involved in diabetesrelated congenital malformations. Indeed, no NTDs were observed in fetuses of diabetic iNos −/− mice and the incidence of other malformations was also markedly reduced. Conclusions/interpretation We conclude that increased iNOS activity during organogenesis plays a crucial role in the pathogenesis of diabetes-induced malformations and suggest that inhibitors of iNOS might help prevent malformations, especially NTDs, in diabetic pregnancy.

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“…Consequently, a growing number of pregnant women have type 1 diabetes and are predisposed to perinatal complications associated with maternal hyperglycaemia, including congenital malformations, macrosomia and fetal asphyxia [3]. Numerous studies indicate that the rates of perinatal complications among type 1 diabetic patients are still substantially higher than those of the general population [4][5][6][7][8][9][10][11]. Only a few centres have shown improvement in the outcomes of type 1 diabetic pregnancies in recent decades [12,13].…”

Section: Introductionmentioning

confidence: 99%

Trends in maternal BMI, glycaemic control and perinatal outcome among type 1 diabetic pregnant women in 1989–2008

et al. 2012

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Aims/hypothesis Our objective was to examine the trends in prepregnancy BMI and glycaemic control among Finnish type 1 diabetic patients and their relation to delivery mode and perinatal outcome. Methods We analysed the obstetric records of 881 type 1 diabetic women with a singleton childbirth during 1989-2008. Maternal prepregnancy weight and height were obtained from the maternity cards, where they are recorded as reported by the mother. Results Maternal BMI increased significantly during 1989-2008 (p<0.001). The mean HbA 1c in the first trimester remained unchanged, but the midpregnancy and the last HbA 1c before delivery increased (p00.009 and 0.005, respectively). Elective Caesarean sections (CS) decreased (p for trend <0.001), while emergency CS increased (p for trend <0.001). The mean umbilical artery (UA) pH decreased in vaginal deliveries (p for trend <0.001). The frequency of UA pH <7.15 and <7.05 increased (p for trend <0.001 and 0.008, respectively). The macrosomia rate remained at 32-40%. Neonatal intensive care unit (NICU) admissions increased (p for trend 0.03) and neonatal hypoglycaemia frequency decreased (p for trend 0.001). In multiple logistic regression analysis, maternal BMI was associated with macrosomia and NICU admission. The last HbA 1c value before delivery was associated with delivery before 37 weeks' gestation, UA pH <7.15, 1 min Apgar score <7, macrosomia, NICU admission and neonatal hypoglycaemia. Conclusions/interpretation Self-reported pregestational BMI has increased and glycaemic control during the second half of pregnancy has deteriorated. Poor glycaemic control seems to be associated with the observed increases in adverse obstetric and perinatal outcomes.

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Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study

Cited by 471 publications

References 13 publications

Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines

Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines

Prevention of neural tube defects by loss of function of inducible nitric oxide synthase in fetuses of a mouse model of streptozotocin-induced diabetes

Trends in maternal BMI, glycaemic control and perinatal outcome among type 1 diabetic pregnant women in 1989–2008

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