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Preconception care for women with pregestational diabetes is associated with better outcomes (10,11). Women with pre-existing vascular complications are more likely to have poor pregnancy outcomes, and there may be progression in the degree of vascular damage (7). Women with type 1 (22,23) and type 2 diabetes (24) should have ophthalmological assessments before conception, during the first trimester, as needed during pregnancy and within the first year postpartum (25,26).
The incidence of hypertension complicating pregnancy is 40% to 45% in women with type 1 and type 2 diabetes (29). There is conflicting information on whether first-trimester exposure to angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) is associated with an increased risk of congential malformations.
Although rare, cardiovascular disease (CVD) can occur in women of reproductive age with diabetes. Care by an interdisciplinary diabetes healthcare (DHC) team composed of diabetes nurse educators, dietitians, obstetricians and diabetologists both prior to conception and during pregnancy, has been shown to minimize maternal and fetal risks in women with diabetes (53–56). An important first step in achieving good glycemic control is to set target glucose levels (2,54).
The limiting factor when seeking euglycemia in women with pregestational diabetes is the increased risk of hypoglycemia during pregnancy, particularly in the first trimester (60–64). Frequent self-monitoring of blood glucose (SMBG) in pregnant women with type 1 diabetes is essential during pregnancy in order to obtain the level of glycemic control associated with better outcomes (57). Insulin Insulin therapy must be individualized and regularly adapted to the changing needs of pregnancy (82–85). CSII While use of CSII may be preferred by some women with type 1 diabetes, studies have not demonstrated superiority over basal-bolus regimen (89,96–99), and, in some studies, there have been more adverse outcomes with CSII (89,99). Oral antihyperglycemic agents and type 2 diabetes A meta-analysis of first-trimester use of either glyburide or metformin and 1 meta-analysis of metformin alone did not show an increased incidence of congenital anomalies (100,101). Metformin and polycystic ovary syndrome Considerable research has been done on the use of metformin in women with polycystic ovary syndrome (PCOS) around the time of conception and during pregnancy.
In summary, higher-level evidence has not shown metformin to be of benefit in women with PCOS in pregnancy.
In order to justify mass screening for a medical disorder, a set of criteria needs to be met (Table 1). There should be an accepted treatment or useful intervention for patients with the disease.
Treatment started at an early stage should be of more benefit than treatment started later. The cost should be economically balanced in relation to possible expenditure on medical care as a whole.
Up until the publication of the 2 large-scale RCTs, the benefit of treatment of varying degrees of hyperglycemia in pregnancy was unclear (119,120). The HAPO study, published in 2008, was a prospective observational study designed to determine if hyperglycemia during pregnancy was associated with an increased risk of maternal or fetal complications, and whether a diagnostic threshold value based on adverse perinatal outcomes could be calculated (4).
Obviously, adopting these recommendations in Canada will profoundly impact the healthcare system, healthcare providers and our pregnant patients. Assuming universal screening, the method of screening can be either a sequential or a 1-step process. The most common glucose test used in sequential screening is the 50 g GCT performed between 24 to 28 weeks of gestation, and it is the screening test recommended by the CDA in the 2008 guidelines. The best data regarding the GCT as a screening test come from the Toronto Tri-Hospital study. An additional question is whether there is a GCT threshold above which GDM can be reliably diagnosed. Those who subscribe to the notion that all cases of hyperglycemia in pregnancy need to be diagnosed and treated (i.e. Given this lack of evidence, it is possible that the decision regarding the recommended screening method will be determined by the economic implications on the healthcare resources.
There are no economic analyses of the impact of the newly proposed IADPSG guidelines, although the impact on workload is expected to be substantial (152). The original criteria for diagnosis of GDM were defined solely on the basis of their ability to identify a prediabetic state in the mother (153). Given the controversy that persists in the international community about the diagnosis of gestational diabetes, there is no clear answer as to what is ideal. During pregnancy, women should be evaluated and followed by a registered dietitian to ensure that nutrition therapy promotes euglycemia, appropriate weight gain and adequate nutritional intake (154–157). Insulin If women with GDM do not achieve glycemic targets within 2 weeks from nutritional therapy alone, insulin therapy should be initiated (177,178). In 2008, Rowan et al (194) studied 751 women with GDM who were randomly assigned to open treatment with metformin (with supplemental insulin if required) or insulin.
When comparing metformin to glyburide, there is a 2:1 failure of control of patients on metformin vs.
The primary goal of intrapartum management is to prevent neonatal hypoglycemia, which is thought to occur from the fetal hyperinsulinism caused by maternal hyperglycemia (202).
Neonatal hypoglycemia There has been much disagreement over the definition of neonatal hypoglycemia because of the lack of rigorous scientific studies. Longer term follow-up found that infants with neonatal hypoglycemia had increased rates of neurological abnormalities at 18 months (208,209) and 8 years of age (210). Risk of neonatal hypoglycemia is related to maternal glucose levels Maternal hyperglycemia during labour, even when produced for a few hours by intravenous fluids in mothers without diabetes, can cause neonatal hypoglycemia (205,211). Insulin requirements decrease intrapartum, and some patients with type 1 diabetes even do not require exogenous insulin to maintain good glucose control during labour (219,220).
Breastfeeding Women with GDM may have more difficulty breastfeeding due to increased operative deliveries and obesity.
Long-term maternal risks With the diagnosis of GDM, there is evidence of impairment of both insulin secretion and action (231,232). Long-term fetal risks There is increasing interest in determining how long the adverse effects of diabetes on pregnancy persist. Information has been collected from the Pima Indians since 1965 examining the impact of maternal diabetes on children and adolescents (270). Since that time, the great majority of studies (270) continue to show an increased risk of obesity and metabolic abnormalities in childhood extending into adolescence and early adulthood (273–275).
How are the long-term consequences of maternal diabetes caused and could they be prevented? LGA infants of diabetic mothers and accelerated third-trimester growth have widely been found to be independent risk factors for offspring obesity and metabolic syndrome (272–283).
Firm conclusions about the benefits of modifying these risk factors are limited by the lack of intervention studies. Women with previous GDM should plan future pregnancies in consultation with their healthcare providers (289,290). 1.All women of reproductive age with type 1 or type 2 diabetes should receive advice on reliable birth control, the importance of glycemic control prior to pregnancy, the impact of BMI on pregnancy outcomes, the need for folic acid and the need to stop potentially embryopathic drugs prior to pregnancy [Grade D, Level 4 (11)].
4.Women with type 2 diabetes who are planning a pregnancy should switch from noninsulin antihyperglycemic agents to insulin for glycemic control [Grade D, Consensus]. 6.Women should be screened for chronic kidney disease prior to pregnancy (see Chronic Kidney Disease chapter, p. 9.Detemir [Grade C, Level 2 (95)] or glargine [Grade C, Level 3 (94)] may be used in women with pregestational diabetes as an alternative to NPH.
11.Women should receive adequate glucose during labour in order to meet their high-energy requirements [Grade D, Consensus]. 12.Women with pregestational diabetes should be carefully monitored postpartum as they have a high risk of hypoglycemia [Grade D, Consensus].
15.All women should be encouraged to breastfeed since this may reduce offspring obesity, especially in the setting of maternal obesity [Grade C, Level 3 (224)].
17.If there is a high risk of GDM based on multiple clinical factors, screening should be offered at any stage in the pregnancy [Grade D, Consensus]. Reference values for 3 hour oral glucose tolerance test Reference values for 3 hour oral glucose tolerance test ogtt perinatology com the 3 hour ogtt is a diagnostic test for gestational diabetes Reference values for 3 hour oral glucose tolerance test. Do you know free movies to watch online now is most likely the hottest topics on this category?
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The American Diabetes Association (ADA) released standards of medical care in diabetes for 2014.
Gestational diabetes increases the risk of gestational hypertension, preeclampsia, cesarean delivery, and developing diabetes later in life. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference.
At conception and during the first trimester, hyperglycemia increases the risk of fetal malformations. The prevalence of pregestational diabetes has increased in the past decade, primarily as a result of the increase in type 2 diabetes (6). Type 1 diabetes is more often associated with preeclampsia and type 2 diabetes with chronic hypertension.
Microalbuminuria and overt nephropathy are associated with increased risk of maternal and fetal complications (34–39). Some (47), but not all (48), cohort studies have demonstrated an increased risk of malformations. Myocardial infarction in pregnancy is associated with poor maternal and fetal outcomes (51,52).
An early working relationship should be established between the woman and the DHC team to optimize care, facilitate the planning of pregnancy, ensure adequate self-care practices and discuss the need for social support during pregnancy.
The risk of severe hypoglycemia ranged from 22% to 71%, with the likely predictors being a history of severe hypoglycemia and hypoglycemic unawareness.
Preprandial determinations, which are needed to guide the meal-time insulin dose adjustment and, postprandial testing to achieve targets are associated with less macrosomia and preeclampsia (58,59,76). Intensive insulin therapy with basal-bolus therapy or continuous subcutaneous insulin infusion (CSII or the insulin pump) is recommended to achieve glycemic targets prior to pregnancy. Therefore, women with type 2 diabetes who find themselves on metformin or glyburide when they conceive should continue these agents until insulin is started. A number of these studies have evaluated metformin for use in ovulation induction and infertility in this population; however, there are conflicting data regarding the benefits of metformin use in this population. The evidence, therefore, does not support the practice of continuing metformin after conception in women with PCOS and normal glucose tolerance. For GDM, screening programs became widespread despite not meeting many of these traditional criteria and, thus, have led to numerous debates regarding the utility and methodology of GDM screening (116,117).
The results of these 2 trials, despite some methodological differences, show a benefit to treatment over no treatment of diagnosed GDM with regard to select perinatal outcomes. This large study (n=23 316) confirmed the findings from 2 previous large-scale, prospective, observational studies (126,127) that the incidence of select adverse maternal and fetal outcomes increases along a continuum of increasing maternal hyperglycemia. The goal of risk factor–based screening would be to ideally identify through historical and clinical risk factors those patients who would benefit most from biochemical screening while allowing those at lower risk to avoid the screening process. Methods for sequential screening include the use of glycosuria, A1C, fasting plasma glucose (FPG), random plasma glucose and a glucose load.
The performance of the GCT as a screening test depends on the cutoff values used, the criteria for diagnosis of GDM and the prevalence of GDM in the screened population. An excellent review of the literature on cost effectiveness of different screening strategies for GDM can be found in Health Technology Assessment 2010. In summary, most cost analysis evaluations support a sequential screening approach to GDM; thus, our preferred approach is to continue with this strategy.
Thus, all of the recent diagnostic thresholds for GDM have been determined by consensus agreement of various national and international professional organizations (see Table 2 ). Ideally, the diagnostic thresholds would be based on their ability to predict clinically relevant perinatal outcomes, such as perinatal mortality, birth trauma or birth asphyxia.
Meal planning should emphasize moderate carbohydrate restriction and distribution over 3 meals and 3 snacks, one of which should be at bedtime.
Both fasting and postprandial testing are recommended to guide therapy in order to achieve glycemic targets (164,165).
In some cases, assessment of fetal growth by early third-trimester ultrasound can be used to guide therapy (179,180).


Women who are older, are diagnosed earlier than 25 weeks and have higher fasting and postprandial glucose values on their OGTT are less likely to respond to glyburide (187,190). Studies have generally been performed in mothers with pregestational diabetes or insulin-treated GDM. There are very few studies (although many published protocols) as to the best method of managing glycemia during labour (221,222).
Women with GDM should be encouraged to breastfeed immediately after delivery and for at least 3 months postpartum, as this may reduce neonatal hypoglycemia and offspring obesity, and prevent the development of metabolic syndrome and type 2 diabetes in the mother (224–230). These defects persist postpartum and increase the risk of impaired fasting glucose, IGT and type 2 diabetes (233,234). Freinkel (268) extended the original Pedersen hypothesis of fuel-mediated teratogenesis to suggest that abnormal metabolism during pregnancy could have long-term effects on the offspring of diabetic mothers (ODM) (269). Children whose mothers had diabetes during pregnancy had a significantly higher incidence of obesity and type 2 diabetes that was detectable by age 9 and persisted into adulthood. Genetics, exposure to abnormal intrauterine metabolism or the family environment all could potentially be involved. Similarly, risk has been shown to be related to maternal glucose levels during pregnancy (281,284,285).
Glucose tolerance should be assessed prior to conception to assure normoglycemia at the time of conception, and any glucose abnormality should be treated.
Women with pregestational diabetes who also have PCOS may continue metformin for ovulation induction [Grade D, Consensus].
S129) [Grade D, Level 4, for type 1 diabetes (39) ; Grade D, Consensus, for type 2 diabetes]. If the initial screening is performed before 24 weeks of gestation and is negative, rescreen between 24 and 28 weeks of gestation. There is debate about the diagnosis and treatment of gestational diabetes, even with large-scale studies on the subject.
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These recommendations have been created in collaboration with the Society of Obstetricians and Gynaecologists of Canada (SOGC). Later in pregnancy, it increases the risk of macrosomia and metabolic complications at birth (1,2). Recent large studies of women with pregestational diabetes continue to show higher rates of complications compared to the general population, including perinatal mortality, congenital malformations, hypertension, preterm delivery, large-for-gestational-age (LGA) infants, caesarean delivery and neonatal morbidities (7–9).
Women who are heavier, younger and smokers, and who have a lower socioeconomic status, lower health literacy and a poor relationship with their healthcare provider, are less likely to receive preconception care (11–14).
Other risk factors for hypertension, such as poor glycemic control in early pregnancy, are potentially modifiable.
An estimated glomerular filtration rate (eGFR) should be used prior to pregnancy to determine risk (40). Women with known CVD should be evaluated and counselled about the significant risks associated with pregnancy. The latter may relate, in part, to the loss of counterregulatory hormones reported in women with pregestational diabetes during pregnancy, particularly growth hormone and epinephrine (65–68). Due to the increased risk of nocturnal hypoglycemia with any intensive insulin therapy, glucose monitoring during the night is often necessary in patients receiving insulin (77). Women using CSII should be educated about the increased risk of diabetic ketoacidosis (DKA) in the event of insulin pump failure because DKA is a potentially fatal complication for the fetus (86).
Lispro does not cross the placenta except at very high doses (>50 units), similar to human insulin (87). A recent meta-analysis of observational studies showed no adverse fetal outcomes in women taking glargine in pregnancy, while maternal outcomes were similar (94). One cohort study of women with type 2 diabetes found an increase in perinatal mortality in women taking metformin compared with insulin; however, the circumstances surrounding these deaths suggest other confounding factors played a role (102). Several observational studies have suggested that metformin may decrease the rate of spontaneous abortions in women with PCOS, prompting many to advocate the use of metformin up to the end of the first trimester or throughout pregnancy in these women (104,105). However, the considerable data available help to confirm the safety of metformin given during pregnancy. A study looking at weight, height and motor-social development up to 6 months of age in children of mothers taking metformin while breastfeeding showed normal development and no difference from formula-fed infants (111). Recent studies and the publication of new guidelines by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) consensus panel have given us the opportunity to revisit the evidence on screening for GDM (118). These findings support the need for a screening strategy for GDM, a largely asymptomatic condition, as there appears to be a beneficial intervention for patients with the disease.
Unfortunately, no outcome-associated glycemic thresholds were identified that could be used to define internationally accepted criteria for the diagnosis of GDM.
Aside from the glucose load, all the other methods mentioned have not been adopted due to their poor performance as screening tests in most populations (133–138). This recommendation is based on a retrospective cohort study in 514 women with a positive 50 g GCT who went on to have a 100 g OGTT (142).
The use of the term screening is misleading in this context as this strategy entails performing the diagnostic test on the entire population at risk. Canadian economic data from a prospective, randomized trial of 3 different screening strategies offers relevant information for the Canadian population (151).
Hypocaloric diets are not recommended, as they result in weight loss and significant ketosis and are likely inadequate in required nutrients, such as protein and calcium.
Thus, until prospective studies of precise targets are available, using the targets in the Maternal-Fetal-Medicine-Unit Network study that were associated with achieving good glycemic control and outcomes appears reasonable (120).
The use of insulin to achieve glycemic targets has been shown to reduce fetal and maternal morbidity (178,181).
Despite the glucose levels, some earlier studies report more adverse outcomes in women treated with glyburide compared to insulin (191,192).
Metformin (alone or with supplemental insulin) was not associated with increased perinatal complications compared with insulin. Mild neonatal hypoglycemia has been found to be associated with transient abnormalities on physical examination (205), neurophysiological testing (206) and brain imaging (207).
These have been observational with no randomized trials deliberately targeting different levels of maternal glycemia during labour.
Rotating intravenous fluids compared with intravenous insulin were no different in controlling maternal glycemia in GDM (223).
The cumulative risk increases markedly in the first 5 years and more slowly after 10 years (235,236). Northwestern University enrolled women with both GDM and pregestational diabetes from 1977 to 1983 and followed their offspring until adolescence. Obesity in adolescence results in an increased risk of metabolic syndrome (277) and coronary artery disease (278). The issue was addressed in the Pima by studying nuclear families with siblings born within 3 years of each other, before and after the mother developed diabetes. In view of the known benefits of breastfeeding and of preventing maternal obesity and LGA infants, it would not be ethical to conduct randomized trials deliberately exposing 1 group to suboptimal levels of 1 of these risk factors. Women with microalbuminuria or overt nephropathy are at increased risk for development of hypertension and preeclampsia [Grade A, Level 1 (39,44)] and should be followed closely for these conditions [Grade D, Consensus]. We took this image from the web that we consider would be probably the most representative pics for 2006 subaru impreza. We took this image on the internet we think would be probably the most representative images for free movies to watch online now. We had taken this picture on the internet we feel would be probably the most representative images for how to unlock outfits advanced warfare.
The American College of Obstetricians and Gynecologists (ACOG) has released a guideline that provides recommendations based on good-quality research and identifies current gaps in knowledge.RecommendationsGOOD AND CONSISTENT EVIDENCEGestational diabetes should be treated with nutrition therapy. As a result, meticulous glycemic control is required for optimal maternal and fetal outcomes. Some, but not all, have shown that women with type 2 diabetes are also less likely to receive preconception care (7,15).
Laser photocoagulation for severe nonproliferative or proliferative retinopathy prior to pregnancy reduces the risk of visual impairment in pregnancy (30). Some (31,32), but not all (33), studies have found that increased urinary protein excretion in early pregnancy raises the risk of developing hypertension. However, during pregnancy, serum creatinine and not eGFR should be used, as eGFR will underestimate GFR in pregnancy (41,42). This risk of hypoglycemia may be ameliorated if efforts are made to achieve good glycemic control preconception and by the use of analogue insulins (64,69,70). Continuous glucose monitoring systems may help identify periods of hyper- or hypoglycemia (78,79) and certainly confirm glycemic variability (80). A randomized trial of detemir use compared with NPH in women with type 1 diabetes has recently been completed, with similar maternal and fetal outcomes in both groups (95).
In another cohort study, there was an increase in perinatal mortality in women taking sulphonylureas, or sulphonylureas plus metformin compared to insulin, but not in those taking metformin alone (103). However, in a meta-analysis of 17 randomized controlled trials (RCTs), metformin use, either alone or with other fertility drugs, had no significant effect on the abortion risk when used preconception (106).
Worldwide, there is currently no agreement regarding the optimal screening strategy for GDM. Despite this, in 2010, the IADPSG consensus panel decided to use the HAPO data to create new diagnostic thresholds for GDM. One cannot directly infer from these studies that there is utility to screening for GDM as they were not designed to assess screening vs. In populations that are older and have increased body mass index (BMI), selective screening ultimately leads to a majority of the pregnant population being screened; thus, universal screening is the pragmatic approach accepted in most North American centers. The 1-step approach includes a 75 g OGTT performed in the fasting state at 24 to 28 weeks of gestation with plasma glucose measured at fasting and 1 and 2 hours after the glucose load. Unfortunately, in this study, no single threshold could be identified that predicted the primary outcome. Prepregnancy body mass is a potent predictor of birth weight and should be considered when making recommendations about energy intake and rate of weight gain (158).
Although the peak for postprandial glycemia occurs at 69 ± 24 minutes (3) and hence may lend support to a 1-hour target being used, in obesity, this peak appears delayed (172). A variety of protocols have been used, with multiple injections being the most effective (182). More recent studies have shown glyburide to be a safe alternative with no dose-related increment in neonatal hypoglycemia (193). There was less severe hypoglycemia in neonates receiving metformin but more spontaneous preterm delivery( i.e.
Most have found that there is a continuous relationship between mean maternal glucose levels during labour and the risk of neonatal hypoglycemia with no obvious threshold. The fact that the risk of the child developing diabetes was significantly higher (OR 3.7) in siblings born after the mother developed diabetes demonstrated that intrauterine exposure per se conveyed the increased risk (279). Studies also have found that adequate breastfeeding is associated with a significant decrease in the risk of childhood obesity (223,283,287). However, it seems reasonable to assume that our current efforts at tight control of maternal nutrition and diabetes during pregnancy and promoting breastfeeding will provide benefits throughout childhood and adolescence. If necessary, medications should also be used to benefit the mother and fetus.Studies show a significant reduction in serious complications with treatment of gestational diabetes. A random albumin to creatinine ratio and serum creatinine should be measured each trimester. Thus, the increased risk of malformations may be more related to the hypertension itself rather than a direct effect of ACE inhibitors and ARBs.
Whether closed loop systems will become practical for use in pregnancy remains to be seen (81).
Cohort studies have shown improved A1C levels and less hypoglycemia in women with pregestational diabetes in pregnancy taking lispro compared with human insulin, while fetal outcomes were similar (88–90). In each of the trials in this meta-analysis, metformin was discontinued at the time of diagnosis of pregnancy.
There are no studies to date looking at thiazolidinedione use, glucagon-like peptide-1 agonist or dipeptidyl peptidase-4 (DPP-4) inhibitor use while breastfeeding; therefore, they should not be taken during breastfeeding. Universal and selective (risk factor based) screening are the most common methods used, but only 1 randomized trial has compared these 2 strategies (121).


It is possible that future analysis of the HAPO data based on GDM risk factors might allow modification of this recommendation (132). Using the data from this study, we need to understand that, by using the sequential 50 g GCT followed by a glucose tolerance test, some 20% of the population will screen positive, of whom 16% will not have GDM.
The IADPSG and the American Diabetes Association (ADA) have supported this option (118,122), while some European guidelines recommend the 75 g OGTT only to women with risk factors but use the IADPSG thresholds for diagnosis of GDM (147–149). The sequential screening strategy was found to be less expensive while having the same diagnostic power as there was no difference in the incidence of GDM in all 3 groups. The continuous association between increasing glucose intolerance and the risk of caesarean section, birth weight >90%, neonatal hypoglycemia and cord C-peptide levels did not permit the determination of new diagnostic criteria. Continuous glucose monitoring systems have been useful in picking up previously undetected hyperglycemia, but it is unproven if they are cost effective (173–175). A recent systematic review of the literature has shown glyburide and metformin have similar outcomes when compared to insulin therapy (201).
Authors have often chosen 2 levels within the range and shown that there is more hypoglycemia with the higher value, but the studies do not arrive at a common value. Given the lack of studies, there are no specific protocols that can be recommended to achieve the desired maternal glucose levels during labour.
While elevated FPG during pregnancy is a strong predictor of early development of diabetes (237,238), other predictors include age at diagnosis, use of insulin, especially bedtime insulin or oral agents, and more than 2 pregnancies (239,240). They found that aberrant maternal metabolism in the second and third trimesters (most often beta-hydroxbutyrate levels) was associated with reduced intellectual and psychomotor development on a number of tests performed up to age 11.
Nutrition therapy includes nutritional counseling, a personalized nutrition plan, and a moderate exercise program, with the goal of achieving normoglycemia, preventing ketosis, facilitating adequate weight gain, and contributing to fetal well-being.If target glucose levels cannot be met with nutrition therapy alone, medical therapy should be initiated.
By discussing pregnancy prior to conception, healthcare providers may be able to improve outcomes by educating women about the importance of strict glycemic control, encouraging folic acid supplementation, discontinuing potentially harmful medications and reducing body weight. A number of antihypertensive medications are known to be safe and effective in pregnancy, including calcium channel blockers, labetalol and methyldopa. Fetal exposure in the second and third trimesters is clearly associated with a fetal renin-angiotensin system blockade syndrome, which includes renal failure, oligohydramnios, hypotension, intrauterine growth restriction and death (50). Maternal hypoglycemia does not increase the risk of congenital malformations in the offspring (53,71,72) or other adverse outcomes (2). Data on glargine are more limited (cohort and case control studies), and theoretical considerations make it less desirable; however, no adverse maternal or fetal effects have been found to date. Currently, a large randomized trial is underway to see if adding metformin to insulin will benefit mothers with type 2 diabetes and their infants (MiTy trial). Other nonrandomized studies have noted benefit in women who used metformin throughout pregnancy (107). In conclusion, metformin and glyburide can be considered for use during breastfeeding, although further long-term studies are needed to better clarify the safety of these drugs. The most common method of screening is with the stepwise 50 g oral glucose challenge test (OGCT) at 24 to 28 weeks of gestation, followed by an oral glucose tolerance test (OGTT) as the diagnostic test if a certain threshold has been surpassed. The utility of screening will vary based on the baseline characteristics of the screened population and the country-specific health economics evaluation. Due to the low sensitivity, almost one-fourth of the patients with GDM will not be diagnosed using this strategy; specifically, the test will not identify those women whose only abnormality is elevated FPG. In March 2013, the National Institutes of Health (NIH) held a consensus development conference to discuss the diagnosis of GDM. This, in itself, is surprising as one would expect the incidence of GDM to be higher in the universally tested group. Physical activity should be encouraged unless obstetrical contraindications exist or glycemic control is worsened by the activity (159,160).
Women with GDM, in an effort to control their glucose by diet, may put themselves and their baby at risk for starvation ketosis.
Although the rapid-acting bolus analogues aspart and lispro can help achieve postprandial targets without causing severe hypoglycemia (181–183), improvements in fetal outcomes have not been demonstrated with the use of aspart or lispro compared to regular insulin (181,182).
Other studies have confirmed the safety of metformin with less neonatal hypoglycemia (195). With respect to growth, neonatal macrosomia had resolved by age 1, and weight was not different from controls until age 5. After examining multiple factors, they found that increased BMI was mediated through an intrauterine mechanism (280).
Although there are no intervention trials to support larger doses of folic acid for women with diabetes, several factors favour recommending a larger dose.
In women with elevated serum creatinine, however, pregnancy can lead to a permanent deterioration in renal function (46). In later pregnancy, maternal hypoglycemia was associated with a nonsignificant increase in fetal movements (73) and had no impact on fetal heart rate (74) and no long-term consequences for the infant (75), although repeated hypoglycemia and associated loss of glycemic control were associated with macrosomia (68). In the meantime, the use of oral agents is not recommended for glycemic control in women with type 2 diabetes during pregnancy.
These arbitrary thresholds, when applied to the HAPO cohort, led to a GDM incidence of 17.8%. We can, therefore, infer from the results of these management studies, along with the data confirming that the incidence of adverse perinatal outcomes increases as glucose intolerance increases, that identification of women with hyperglycemia in pregnancy has clinical significance. The performance of the 50 g GCT can be improved when slightly more complicated strategies are used, such as factoring in certain risk factors, ethnic background or time from last meal (139–141). The authors also indicate that these results might not be applicable to higher-risk ethnic populations (151). Use of these new thresholds without subjecting them to rigorous clinical evaluation will lead to a significant increase in the number of women labeled as having GDM.
Therefore, an alternative approach would be 1-step 75 g OGTT using the glucose thresholds that result in an OR of 1.75 (IADPSG recommended criteria) ( Figures 1 and 2 ). Older studies raised the possibility that elevated ketoacids may be detrimental to the baby (75,176). A recent analysis reveals that glargine is safe in pregnancy and can be considered an option for pregnant patients (184). While metformin appears to be a safe alternative to insulin therapy, it does cross the placenta, plus metformin clearance is increased in pregnancy (196). From age 5 through 16, the BMI of ODM (both GDM and pregestational diabetes) was significantly higher than in control subjects (271).
Obesity, which is more common in women with type 2 diabetes, is associated with lower serum folate levels for the same intake, lower intake of folate rich foods and increased risk of neural tube defects independent of glucose (18,19,20). Perinatal outcomes were similar using insulin aspart and human insulin; however, the study was not powered to show differences in these outcomes (91). A recent Cochrane review of randomized trials found that although metformin was effective in improving ovulation rates and pregnancy rates in women with PCOS, both alone and in combination with clomiphene, this did not translate into a significant increase in live births (108). As hyperglycemia in pregnancy is an asymptomatic condition, diagnosis is dependent on some form of screening. As with all aspects of hyperglycemia in pregnancy, there is evidence that along a continuum of GCT results without a diagnosis of GDM, there is an increase in certain adverse perinatal outcomes (146). This draft statement stated that, as of that time, the NIH panel did not find sufficient evidence to support adopting a 1-step approach, such as that proposed by IADPSG (150). This might prove to have a clinical benefit, but there is also the possibility of causing harm through unnecessary interventions, increased anxiety and an effect on women’s perceptions of their health. While the clinical significance of these findings are doubtful, it appears prudent to check that urine ketones are negative when focusing on diet therapy for GDM. A recent Canadian review of rapid and long-acting basal analogues in GDM for glycemic control and hypoglycemia did not shown superiority (185). Results of the offspring follow-up of the Metformin in Gestational diabetes trial (Mig TOFU), expected in several years, will provide more data on the long-term safety of metformin. Finally, glucose levels in obese, nondiabetic pregnant women were slightly higher than their lean counterparts (5).
Using a mathematical model, a 5 mg intake will be more effective in reducing neural tube defects in this vulnerable population (21). At this point, there is no evidence supporting a specific cutoff value of the 50 g GCT to diagnose GDM.
Some women with GDM, especially lean women <30 years of age who require insulin during pregnancy, progress to type 1 diabetes (244,245).
Metformin also has been associated with improvement in other pregnancy outcomes, including prevention of GDM, in observational studies (109).
Women with positive antibodies (anti-glutamic acid decarboxylase (anti-GAD), anti-insulinoma antigen 2 (anti-IA2)) are more likely to have diabetes by 6 months postpartum (246). If early screening results are negative, screening should be repeated at 24 to 28 weeks' gestation. However, in a recent, randomized, placebo-controlled trial of metformin treatment started in the first trimester of pregnancy in women with PCOS, metformin failed to reduce the rates of preeclampsia, GDM, preterm delivery or a composite of the 3 outcomes (110). There are no data regarding the performance of combinations of risk factor–based screening and a 75 g OGTT or sequential 50 g GCT followed by a 75 g OGTT using the new IADPSG criteria.
Postpartum testing is essential to identify women who continue to have diabetes, those who developed diabetes after temporary normalization and those at risk, including those with IGT.
The screening approach widely used in the United States involves an initial venous glucose measurement one hour after administration of 50 g of oral glucose solution. Only 1 study to date has looked at longer-term outcomes in women with PCOS taking metformin in pregnancy. However, many women do not receive adequate postpartum follow-up, and many believe they are not at high risk for diabetes (247–249). Women who meet or exceed the screening threshold in the initial test then undergo a 100-g, three-hour oral glucose tolerance test.Although there are insufficient data to recommend for or against cesarean delivery in cases of suspected macrosomia to reduce birth trauma, macrosomia is more common with gestational diabetes, and shoulder dystocia is more common in larger newborns whose mothers have gestational diabetes. This small study found no increase in the rate of abnormal growth and motor development in infants at 18 months of age (111).
It is essential that the importance of follow-up be explicitly communicated with women and their caregivers who are responsible for postpartum testing.
Because there is no clear evidence to determine the best threshold, physicians should select either 135 mg per dL (7.5 mmol per L) or 140 mg per dL as a single consistent cutoff for their practice.
Factors such as community prevalence of gestational diabetes should be considered in the decision.
Similarly, no one set of diagnostic criteria can be recommended for the three-hour oral glucose tolerance test.
Postnatal fasting blood glucose has been the most consistently found variable in determining women at high risk for early postpartum diabetes (254).
Although there is insufficient evidence to determine the optimal frequency of glucose monitoring, the general recommendation is four times daily (fasting and one or two hours after each meal). Women should be counselled that the recurrence rate of GDM is high, from 30% to 84%, in subsequent pregnancies (258,259). Monitoring can be adjusted after glucose levels are well controlled by diet.Women with gestational diabetes who have good glycemic control and no other complications can be treated expectantly.
Most women with good glycemic control on medical therapy do not require delivery before 39 weeks' gestation.All women with gestational diabetes should be screened six to 12 weeks postpartum for diabetes, impaired fasting glucose, or impaired glucose tolerance.
Given the increased risk of CVD with metabolic syndrome, consideration should be given for screening for all components of metabolic syndrome in the postpartum care of women with GDM, specifically if there is a family history (263,264). Women with positive screening results should be referred for preventive therapy, and women with negative screening results should receive follow-up testing every three years. High C-reactive protein, high low-density lipoprotein, fibrinogen and uric acid have been described postpartum in women with a history of GDM (265).
A fasting plasma glucose test or a 75-g, two-hour oral glucose tolerance test is appropriate for postpartum screening.Guideline source: American College of Obstetricians and GynecologistsEvidence rating system used?
Education on lifestyle modification to prevent diabetes and CVD should begin in pregnancy and continue postpartum. Awareness of exercise for prevention of diabetes is low (266), and emphasis on targeted strategies that incorporate women’s exercise beliefs may increase participation rates (267).



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