Different intensities of glycaemic control for pregnant women with pre-existing diabetes

ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, Australia, 5006.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 09/2010; 9(9):CD008540. DOI: 10.1002/14651858.CD008540.pub2
Source: PubMed


Women who have either type 1 or type 2 diabetes before they become pregnant have an increased risk of pregnancy loss, high birthweight babies and perinatal deaths. The metabolic disruptions to the fetus caused by the mother's high blood sugars and insulin resistance can affect the development of organs, and cardiovascular malformations are the most common birth defects in infants born to diabetic mothers. Infants of diabetic mothers may also be at increased risk of developing obesity and type 2 diabetes. Management of diabetes in pregnancy therefore aims for tight control of glucose (glycaemic control) using careful combinations of diet, exercise, insulin or other anti-diabetogenic drugs, clinical visits and monitoring. We identified only three small trials (in a total of 223 pregnant women with type 1 diabetes) looking at different intensities of glycaemic control. We found very few differences between very tight and tight to moderate glucose targets in two trials, although there were significantly more cases of low blood sugar (hypoglycaemia) and longer hospital stays for women who had very tight blood sugar control. A single trial comparing tight, moderate and loose blood glucose targets found few differences between the tight and moderate groups, although significantly more women in the tight control group had hypoglycaemia in the first half of pregnancy. In the loose control group, significantly more women had pre-eclampsia, and there were significantly more caesareans and large babies. It is clearly difficult for women to achieve glucose targets in isolation, and interventions such as monitoring may be successful in helping women to manage their diabetes.

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Available from: Philippa Middleton
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    • "Hyperglycemia, hypoglycaemia and variability in clinical management protocols may affect perinatal outcomes [21-23]. However, it remains uncertain which treatment modality is associated with optimal perinatal outcomes [24,25], and data specific to multiple pregnancies remain absence. Further studies are needed to clarify the effects of glycemic control on perinatal outcomes in diabetic pregnancy. "
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    ABSTRACT: Diabetes in pregnancy has been associated with a paradoxically reduced risk of neonatal death in twin pregnancies. Risk "shift" may be a concern in that the reduction in neonatal deaths may be due to an increase in fetal deaths (stillbirths). This study aimed to clarify the impact of diabetes on the risk of perinatal death (neonatal death plus stillbirth) in twin pregnancies. This was a retrospective cohort study of twin births using the largest available dataset on twin births (the U.S. matched multiple birth data 1995-2000; 19,676 neonates from diabetic pregnancies, 541,481 from non-diabetic pregnancies). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death accounting for twin cluster-level dependence. Comparing diabetic versus non-diabetic twin pregnancies, overall perinatal mortality rate was counterintuitively lower [2.1% versus 3.3%, aHR 0.70 (95% confidence intervals 0.63-0.78)]. Individually, both stillbirth and neonatal mortality rates were lower in diabetic pregnancies, but we identified significant differences by gestational age and birth weight. Diabetes was associated with a survival benefit in pregnancies completed before 32 weeks [aHR 0.55 (0.48-0.63)] or with birth weight <1500 g [aHR 0.61 (0.53-0.69)]. In contrast, diabetes was associated with an elevated risk of perinatal death in pregnancies delivered between 32 and 36 weeks [aHR 1.38 (1.10-1.72)] or with birth weight >=2500 g [aHR 2.20 (1.55-3.13)]. Diabetes in pregnancy appears to be "protective" against perinatal death in twin pregnancies ending in very preterm or very low birth weight births. Prospective studies are required to clarify whether these patterns of risk are real, or they are artifacts of unmeasured confounders. Additional data correlating these outcomes with the types of diabetes in pregnancy are also needed to distinguish the effects of pre-gestational vs. gestational diabetes.
    Preview · Article · Sep 2013 · PLoS ONE
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    • "Both incomplete spiral arterial modification, and aberrant NK cell numbers, functions, or ratios to other immune cell types have been linked with pre-eclampsia (PE), fetal growth restriction (IUGR), and with recurrent pregnancy losses (Hiby et al., 2004; Ledee et al., 2008; Quenby et al., 2009; Rieger et al., 2009). This trio of pathologies occurs more frequently in diabetic than in healthy women, even in the presence of good glycemic control (Middleton et al., 2010). "
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    ABSTRACT: Human uterine natural killer (uNK) cells, the dominant lymphocytes in early pregnancy decidua, are important for spiral arterial remodelling. uNK cells are thought to arise from circulating CD56(bright) NK cells that egress into decidualizing endometrium. Both incomplete spiral arterial modification and aberrant NK cell function have been linked with pre-eclampsia, a syndrome that is more prevalent in diabetic women. Since previous in vitro studies have shown that changes in decidual endothelium induced by type 1 diabetes (T1D) reduce its interactions with circulating leucocytes, we hypothesized that diabetes additionally has direct effects on circulating CD56(+) NK cells that impair their decidual homing potential. Serial blood samples were collected from control, T1D and T2D pregnant women throughout and after pregnancy. In vitro adhesion under shear forces was used to assay the functional capacity of circulating leucocytes and of CD56(+) cells to adhere to endothelium in cryostat sections of gestation day (gd) 7 normal mouse decidua, pancreas and lymph node. Fewer CD56(+) cells from diabetic compared with control women adhered to normal decidual endothelium. The CD56(+) cell/total cell adhesion ratio was also lower in diabetics. More diabetic CD56(+) cells adhered to pancreatic endothelium and their proportion was greater than for controls. Neither absolute nor proportional adhesion of CD56(+) cells to lymph node endothelium differed between diabetics and controls. The CD56(+) cell adhesion patterns of T1D and T2D women differ from those of non-diabetic women and support the hypothesis that diabetes impairs mechanisms that could be used by CD56(+) cells for egress into decidua.
    Preview · Article · Jul 2011 · Human Reproduction
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    ABSTRACT: Pregnant women with diabetes have to manage both the effect of pregnancy on glucose control and its effect on pre-existing diabetic complications. Most women experience hypoglycaemia as a consequence of tightened glycaemic control and this impacts on daily living. Less commonly, diabetic ketoacidosis, a serious metabolic decompensation of diabetic control and a medical emergency, can cause foetal and maternal mortality. Microvascular complications of diabetes include retinopathy and nephropathy. Retinopathy can deteriorate during pregnancy; hence, regular routine examination is required and, if indicated, ophthalmological input. Diabetic nephropathy significantly increases the risk of obstetric complications and impacts on foetal outcomes. Pregnancy outcome is closely related to pre-pregnancy renal function. Diabetic pregnancy is contraindicated if the maternal complications of ischaemic heart disease or diabetic gastropathy are known to be present before pregnancy as there is a significant maternal mortality associated with both of these conditions.
    No preview · Article · Feb 2011 · Best practice & research. Clinical obstetrics & gynaecology
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