El problema psicológico como dificultad de adaptación. I:

The goal of treatment in women with GDM is to achieve blood glucose level control.

Diabetic control in pregnancy and obstetric management will be associated with a reduction in the severity of neonatal complications and improve the adverse outcomes for the mother. In terms of the management of GDM, effective treatment demonstrates that diagnosis and treatment of GDM results in a reduction in adverse effects for both mother and child. In two randomized control trials, it has been shown that interventions

in women diagnosed with GDM using dietary advice, monitoring and management of blood glucose, are effective in reducing birth weight, the rate of growth for gestational age infants, and perinatal morbidity. The authors of the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS), a large randomized control trial (RCT) of treatment for GDM, concluded that treatment of GDM reduced the risk of serious perinatal complications and may also improve women’s health-related quality of life during pregnancy and after delivery (Crowther et al., 2005). The authors of another RCT in 2009, The Maternal Foetal Medicine Units network (MFMU) study, found that treatment of mild GDM did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications but did reduce the risk of foetal overgrowth, shoulder dystocia, caesarean section, and hypertensive disorders (Landon et al., 2009). In the ACHOIS, a significant decreased risk in the composite outcome was demonstrated, but in the MFMU study the risk of composite outcome was not significantly different. The authors of a systematic review of treatment of women with GDM stated that treatment for GDM, including treatment to control blood glucose alone or with other specific treatment, seems to lower the risk for some perinatal complications in both mother and child (Horvath et al., 2010). In addition, untreated carbohydrate intolerance during pregnancy was associated with increased risk of maternal and perinatal morbidity (Pettitt et al., 1980). Bellamy and colleagues found that proper tests and management such as dietary, lifestyle and pharmacological intervention, might prevent or delay the onset of type 2 diabetes in women with GDM (Bellamy et al., 2009).

There are a substantial number of treatments for GDM. This review divides these into two main groups, non-pharmacological and pharmacological, based on the Scottish Intercollegiate Guidelines Network for the management of diabetes (SIGN) and the National Institute for Health and Clinical Excellent (NICE) guidelines for antenatal care diabetes in pregnancy (SIGN, 2010) (NICE, 2008d). Management of GDM in these guidelines are the same, including dietary therapy and blood glucose monitoring on the one hand, and pharmacotherapy (Glibenclamide and Metformin) or insulin therapy (Regular insulin, Insulin aspart and Insulin lispro).

4.6.1 Dietary therapy

Dietary therapy is the primary GDM treatment strategy for controlling glucose levels and ensuring appropriate maternal weight gain. A good diet is important for women during pregnancy, as food provides the mother’s energy requirement and supplies the foetus with the nutrients it needs to develop. All women should receive nutritional advice from an appropriately skilled dietician. For women with diabetes before pregnancy,

pre-pregnancy nutritional assessment and care from a dietician may improve the patient’s chance of achieving the best possible diabetes control before conception. Dietary programmes need to conform to the principles of dietary management of diabetes in general and meet the nutritional requirements of pregnancy. In addition, dietary therapy should be individually tailored for each woman with GDM and take account of maternal weight and body mass index. The dietary recommendations generally include avoiding sugar, convenience foods and junk foods. Small frequent meals and a very small breakfast should be eaten and fat intake reduced. Generally, daily calorie needs for women of normal weight in the second half of pregnancy are 30 – 32 kcal per kilogram of body weight. Dietary therapy plans control blood sugar by controlling the amount of carbohydrate food consumed during a day. Eating less carbohydrate may decrease blood sugar level. Some carbohydrates are digested more slowly and raise blood sugar level more than others (Diabetes prevention and control program, 2007).

Carbohydrate counting for meals and snacks are considered in most dietary programme recommendations. The American Diabetic Association (ADA) recommends an intake of calories and nutrients sufficient to decrease maternal hyperglycemia. The dietary programme recommended a 30-33% reduction of calories for those pregnant with diabetes, with at least 40% daily carbohydrate intake. The ideal allocation would be 50-60% carbohydrates (complex and high fiber), 10 -20 % protein, and 25 - 30 % fat (<

10% saturated). In 2003, the British Diabetic Association recommended not less than 45% carbohydrates with a low glycaemic index, and a limited proportion of dietary fats.

The Fifth Workshop Conference on GDM in Chicago in November 2005 suggested an optimal carbohydrate content in pregnancy of 175 g/day including 140g for the mother and 35g for foetal brain metabolism (Cianni D G et al., 2008).

Major and co-workers found that women with GDM who received dietary treatment and who obtained less than 40 percent of their total calories from carbohydrates, had babies with lower birth weights and had lower risk of caesarean delivery than women with higher intakes(Major et al., 1998). Magee and colleagues, who performed a randomized control trial in obese women with GDM, stated that restriction of carbohydrates by 50% (1,200 kcal/day) improved glycaemic control but, significantly increased the risk of ketonemia and ketonuria (Magee et al., 1990). The authors of a systematic review of the evidence for screening for GDM found that more than 70% of patients with GDM have mild hyperglycemia and are usually treated with diet alone (Brody et al., 2003).

4.6.2 Blood glucose Monitoring

Once patients with GDM start a dietary programme, it is important to monitor capillary blood glucose levels. Patients and health care providers have to increase the frequency of the monitoring of daily blood glucose levels. Monitoring the blood glucose is important in evaluating the efficacy of the exercise and eating programme by testing blood sugar levels at the proper times during each day. In the self-monitoring of blood glucose, a drop of blood is tested for blood glucose levels by using a special device. Patients should do this test three times a day, as shown in Table 4.2. Occasionally, some patients may ask to test more frequently during a day or at night.

The Australasian Diabetes in Pregnancy Society (ADIPS) recommends self-monitoring of blood glucose, obtaining at least one fasting and one 1 or 2 hour postprandial (5.5, 8.0 and 7.8 mmol/L respectively) tests daily (Hoffman et al., 1998).

The Fourth International Workshop Conference on Gestational Diabetes Mellitus suggested maintaining fasting blood glucose concentrations at less than 5.3 mmol/L, and for one or two hours after a meal at less than 7.8 and 6.7 mmol/L respectively, glucose levels which are lower than ADIPS (Metzger and Coustan, 1998). The clinical practice recommendation of the American Diabetes Association (ADA) on GDM is to perform fasting glucose 5.8 mmol/L and 2-hour postprandial plasma glucose 6.7 mmol/L tests. Self-monitoring of blood glucose in glycaemic control is a controversial issue (American Diabetes Association, 1997). Several studies had shown that more frequent self-monitoring improved glycaemic control. Postprandial hyperglycemia is more closely related to fetal macrosomia than preprandial hyperglycemia in pregnancy with diabetes.

In one randomised study of postprandial and preprandial blood glucose monitoring in women with GDM who required insulin treatment, patients who measured their glucose levels after a meal had infants with lower birth weight, and had fewer caesarean deliveries (de Veciana et al., 1995).

Table 4.2 Treatment targets for women with gestational diabetes mellitus according to the guidelines for self-monitoring blood glucose levels, because of a lack of effectiveness of dietary therapy in controlling these levels. The decision regarding starting insulin therapy differs greatly from centre to centre and is based on many factors, including effectiveness of screening, local incidence, mode of surveillance, individual obstetrical, medical and psychosocial factors, and local resources (Firth, 1996).

Various criteria have been proposed for starting insulin therapy in women with GDM. The American College of Obstetricians and Gynaecologists Committee (ACOG) recommends insulin therapy for women whose fasting glucose level is over 5.2 mmol/L, whose one-hour postprandial glucose level is over 7.1 to 7.7 mmol/L, or whose two-hour postprandial glucose level is over 6.6 mmol/L (ACOG 2001). The ADA recommends a higher glucose level for starting insulin therapy: between 5.0 to 5.5 mmol/L in the fasting state, less than 7.7 mmol/L at one hour after eating, and less than 6.65 to 7.05 mmol/l at two hours after eating (Metzger et al., 2007). Buchanan and colleagues recommend initial insulin therapy to reduce risk of macrosomia when abdominal circumference (AC) measured by ultrasound is higher than the 75^th percentile for gestational age (Buchanan et al., 1994).

Insulin is the first-line pharmacologic therapy for GDM. Human insulin has several theoretical and practical advantages for GDM. It does not cross the placenta and is highly effective. In gestational diabetes, mothers require insulin for the duration of

the pregnancy period (Firth, 1996). Regular insulin, which is used in pregnancy for treatment of diabetes, has some limitations: it becomes effective from 30 – 60 minutes after subcutaneous injection, the effect peaks after 2 – 3 hours and the duration of the effect is too great (about 8 – 10 hours). Currently available insulin analogues include rapid-action mealtime insulins Lispro (Humalog) and Aspart (Novolog), and long-acting basal insulin Glargine (Lantus). Mealtime insulins (Lispro, Aspart) are used to control post-meal blood glucose level. For controlling between-meal and overnight blood glucose levels a basal insulin is used (NPH, Glargine, Lente and Ultralente). Lispro and Aspart are categorised as class B drugs in The United States of America. However, ACOG and the ADA have not yet officially recommended their use. In contrast to Lispro and Aspart, there is little information on the use of the long-acting insulin analogues Glargine (Lantus) and Detemir (Levemir) in pregnancy. HPN is the intermediate-acting option of choice for those who require pharmacologic treatment.

Initially, the insulin dose can be calculated on the basis of the patient’s weight.

The first doses depend on gestational age, capillary blood glucose monitoring levels, current body weight at the start of therapy, further adjustments, base activity, meal plan and other factors, as shown in Table 4.3. Most gestational diabetic patients require an insulin dose of 0.6 U/kg body weight or more. Patients may safely be given an initial total daily dose of 0.4 U/kg by giving two-thirds of it in the morning and one-third in the evening (Firth, 1996). The normal dose for diabetes patients is 0.8 U/kg, and 0.9 -1.0 U/kg for overweight and obese women.

Table 4.3 Total suggested daily insulin during pregnancy Gestational weeks Total daily insulin

Week 1-18 0.7 U/kg actual body weight Week 18 – 26 0.8 U/kg actual body weight Week 26 – 36 0.9 U/kg actual body weight Week 36 – 40 1.0 U/kg actual body weight

In most, but not all, prospective trials of insulin therapy in women with GDM, a reduction has been shown in the risk of neonatal macrosomia (Turok et al., 2003).

Coustan and Lewis reported that treatment of women with diabetes with insulin (20 units NPH and 10 Units regular) was effective in reducing the incidence of foetal macrosomia (Coustan and Lewis, 1978). Similarly, the authors of a study in Alabama in 1990 using the same insulin dose reported a successfully reduced mean birth weight, macrosomia rate, and ponderal index (Thompson et al., 1990). In contrast, little effect on birth weight, birth trauma, operative delivery, or neonatal metabolic disorder was found in a randomised controlled trial of intensive treatment of GDM (Garner et al., 1997).

4.6.4 Pharmacotherapy

Oral hypoglycaemic agents are not currently used in treating GDM because these medications cross the placenta and could stimulate the foetal pancreas. For this reason, tolbutamide, chloropropamide, and other sulfonylureas are not used in pregnancy (Langer, 1993) (Hoffman et al., 1998). Nevertheless, glyburide therapy is an alternative for women who are unable or unwilling to take insulin, and is recommended in several practices as a first-line therapy (Serlin and Lash, 2009). Glyburide, an oral glucose lowering agent often used in the treatment for type 2 Diabetes mellitus, has been shown not to cross the placenta and has been studied for use in pregnant women (Elliott et al., 1994). Moore stated that the safety of glyburide is difficult to establish because of the relatively small number of patients with GDM in the study (Moore, 2007).

201 glyburide-treated women were compared to 203 insulin-treated women. The study showed gyburide to be a clinically effective alternative to insulin therapy in women with GDM (Langer et al., 2000). In a secondary analysis of a previous paper by Langer and co-workers, it was also found that glyburide and insulin are equally efficient in the treatment of GDM at all levels of disease severity (Langer et al., 2005). In addition, metformin (Glucophage) may be another option for treatment of GDM. In a randomised controlled trial of 751 women with diabetes in urban obstetrical hospitals in New Zealand and Australia, in which treatment with metformin (plus insulin, if needed) and treatment with insulin alone were compared, neither were associated with an increase in perinatal complications (Rowan et al., 2008). In another randomised study, metformin was compared with insulin treatment in patients with GDM. Rowan and colleagues reported that glycaemic control in patients with GDM treated with metfomin and/or insulin was strongly related to pregnancy outcomes (Rowan et al., 2010).

During pregnancy, the NICE and SIGN guidelines recommend that women with GDM receive interventions that include dietary control, home glucose monitoring and pharmacotherapy, as well as insulin therapy when needed (SIGN, 2010) (NICE, 2008d).

Pharmacotherapy or insulin should be considered when dietary therapy results are ineffective in controlling blood glucose levels, when there is a lack of expected weight loss following calorie restriction, or when patients are consistently hungry (Serlin and Lash, 2009). GDM treatment should be focused on the prevention of both mother and foetal complications (Kjos and Buchanan, 1999). A team focused treatment for managing GDM in women is ideal, if possible. The teams would usually include an obstetrician, diabetes physician, a diabetes educator (diabetes midwifery educator), dietician, midwife and paediatrician. The number of maternal care visits per mother is significant in confirming whether GDM is being managed properly. Bryson and colleague stated that where the number of maternity clinic visits were 80% less than expected,

women with GDM were found to have a higher risk of both eclampsia (convulsions from high blood pressure) and preeclampsia (swelling of kidney problems from high blood pressure) than women with GDM who complete prenatal care (Bryson et al., 2003).

Women with GDM should be closely monitored until the early postpartum period.

4.7 Guidelines: screening and diagnostic test thresholds