Current Management of Gestational Diabetes Mellitus

Guido Menato; Simona Bo; Anna Signorile; Marie-Laure Gallo; Ilenia Cotrino; Chiara Botto Poala; Marco Massobrio

Disclosures

Expert Rev of Obstet Gynecol. 2008;3(1):73-91. 

In This Article

Treatment of Gestational Diabetes Mellitus

Diet is the mainstay of treatment in GDM whether or not pharmacologic therapy is introduced. Dietary control with a reduction in fat intake and the substitution of complex carbohydrates for refined carbohydrates seeks to achieve and maintain the maternal blood glucose profile essential during gestation. Two approaches are recommended: decreasing the proportion of carbohydrates to 40% in a daily regimen of three meals and three or four snacks, or lowering the glycemic index so that carbohydrates make up approximately 60% of the daily intake.[9,10,11,12]

The ADA also recommends nutritional counseling, if possible by a registered dietitian, with individualization of the nutrition plan based on height and weight.[13]

For normal-weight women (BMI: 20-25 kg/m2) 30 kcal/kg should be prescribed; for overweight and obese women (BMI > 24-34 kg/m2) calories should be restricted to 25 kcal/kg, and for morbidly obese women (BMI > 34 kg/m2) calories should be restricted to 20 kcal/kg or less.[12] In normal pregnancy expected weight gain varies according to the prepregnancy weight. The Fifth International Workshop-Conference on GDM recommends a relatively small gain during pregnancy of 7 kg (15 lb) or more for obese women (BMI ≥ 30 kg/m2) and a proportionally greater weight gain (up to 18 kg or 40 lb) for underweight women (BMI < 18.5 kg/m2) at the onset of pregnancy. However, there are no data on optimal weight gain for women with GDM.[14] Caloric composition includes 40-50% from complex, high-fiber carbohydrates, 20% from protein, and 30-40% from primarily unsaturated fats. The calories may be distributed 10-20% at breakfast, 20-30% at lunch, 30-40% at dinner and 30% with snacks, especially a bedtime snack in order to reduce nocturnal hypoglycemia.[15]

Caloric restriction should be approached with caution, because two studies have reported a relationship between elevated maternal serum ketone levels and reduced psychomotor development and IQ from the third to the ninth year of age in the offspring of mothers with GDM.[16,17] Levels of glucose, free fatty acids and ketone bodies have been assessed during each trimester in long-term follow-up studies of infants of women with and without diabetes. These studies have reported an inverse association between maternal circulating levels of ketone acids in the second and the third trimesters and psychomotor development and intelligence in the offspring at 3-5 years of age through to 9 years of age.[16,17] Even when investigators re-evaluated their findings by taking into account socioeconomic status, race or ethnicity and the presence of gestational or pre-existing diabetes, this association persisted. Although the correlation between IQ and ketone levels was weak, it was statistically significant; therefore, it would be prudent to avoid excessive ketonemia or ketonuria during pregnancy.[18]

Very few studies or reports on the effects of physical activity for the prevention or treatment of gestational diabetes are available at present.

Research has shown that the most physically active women have the lowest prevalence of GDM.[19]

Dempsey et al. in a prospective study and in a case-control study showed that lean as well as overweight women who were physically active before and/or during pregnancy experienced statistically significant reduced risks of GDM (48% risk reduction). Compared with inactive women, women who participated in any physical activity the year before pregnancy experienced a 56% risk reduction of GDM.[20,21] In 2006, Zhang et al. found that vigorous physical activity before pregnancy and continuation of activity during early pregnancy may reduce the risk of developing abnormal glucose tolerance and GDM.[22]

The ADA has endorsed exercise as 'a helpful adjunctive therapy' for GDM when euglycemia is not achieved by diet alone.[23,24] Dietary strategies are the mainstay of therapy for patients with GDM. However some women suffering from GDM cannot be managed with diet alone to optimize pregnancy outcomes and need to use insulin. Insulin corrects hyperglycemia without affecting peripheral insulin resistance. Thus, the most appropriate intervention would be exercise, which affects insulin resistance and, in the absence of either medical or obstetric complications, is certainly the most suitable intervention for GDM women.[25]

In 1985, Artal et al. conducted the first pilot study on the efficacy and safety of an exercise program in pregnant patients with GDM. It culminated with the following recommendation by the Second International Workshop-Conference on Gestational Diabetes Mellitus: women with an active lifestyle may continue a program of moderate exercise under medical supervision during the pregnancy.[26] In 1989 Jovanovic-Peterson et al. published a study that tested the use of arm ergometry for 6 weeks as a method to improve glucose tolerance in women with GDM.[27]

In another study, Avery et al. (1997) randomized a group of women into an exercise-training program and diet versus diet alone. In contrast to the Jovanovic-Peterson study, they did not identify significant metabolic effects due to exercise.[28] In 2001, the American College of Obstetricians and Gynecologists (ACOG) suggested that 'women with GDM who lead an active lifestyle should be encouraged to continue a program of exercise approved for pregnancy'.[29] In 2004, the ADA suggested encouraging women without medical or obstetrical contraindications to start or continue a program of moderate exercise as part of treatment against GDM. Avery and Walker showed that, compared with rest, a single period of 30 min of cycle exercise at 35% of VO2 max improved glucose excursion.[25] In 2004, Brankston et al. found that exercised overweight women were less likely to need insulin compared with overweight women who received only a diet intervention.[30]

The Cochrane Collaboration has recently carried out a meta-analysis on physical activity in pregnant women with GDM. Four trials involving 114 women with GDM were included in the review. Women were recruited during the third trimester of pregnancy and the intervention was performed for approximately 6 weeks. The authors found no significant difference between exercise and no exercise and between exercise and insulin in all the outcomes evaluated (perinatal outcomes, pregnancy complications and maternal morbidity). The conclusion is that there is insufficient evidence to recommend, or advise against, pregnant women with GDM enrolling in exercise programs. Even if exercise is not beneficial during pregnancy, this change in lifestyle may persist after delivery and may help to prevent the onset of Type 2 diabetes and its long-term complications.[31]

Therefore, exercise is considered to be a valuable adjunctive therapy and preliminary results are encouraging. However, until guidelines from well-controlled studies are unavailable, the actual effectiveness of a specific structured exercise program remains unknown.[32]There are no specific guidelines on exercise useful to prevent and manage pregnancies complicated by gestational diabetes. As for pregnancy without complications, it is possible to follow the ACOG guidelines.

There are no data that support preventing pregnant women from participating in many activities, although some activities carry more risk than others (see "Guidelines of the ACOG for Exercise During Pregnancy").[33] "Contraindications to Aerobic Exercise During Pregnancy" lists the absolute and the relative contraindications to aerobic exercise during pregnancy. Similarly to any form of exercise prescription, these recommendations also include the warning signs to terminate exercise while pregnant.[29]

Dietary therapy is the key element in treating patients with GDM. Once patients start a dietary therapy, it is important that capillary glucose levels are monitored to determine the efficacy of this treatment. Patients should check their fasting and 1- or 2-h glucose levels after each meal.[34] There is neither objective evidence nor a clinical guideline to support the frequency for glucose monitoring in patients with diet-controlled gestational diabetes.[35] A large, prospective trial compared seven-times-daily self-glucose monitoring using memory-based reflectance meters to weekly fasting and 2-h laboratory glucose determinations supplemented by four-times-daily self-monitoring with only test strips and no meters. Although daily self-glucose monitoring has not been demonstrated to reduce perinatal mortality in women with GDM, it appears to be useful in reducing potentially adverse outcome such as macrosomia.[36]

In nonpregnant individuals, diabetes is most often managed using preprandial glucose determinations.[37] However, the fetus may be more sensitive to glucose excesses than to the nadirs of glucose values at different moments of the day. A randomized trial compared preprandial to 1-h postprandial glucose measurements: glycohemoglobin levels, macrosomia, neonatal hypoglycemia and caesarean deliveries were significantly lower among those who had postprandial monitoring.[38]

Recently the newly available technology of continuous glucose monitoring (CGM) has been developed. The CGM measures interstitial glucose levels in subcutaneous tissue within a range of 50-400 mg/dl every 5 min. CGM can accurately detect high postprandial blood glucose levels and nocturnal hypoglycemic events that may go unrecognized by intermittent blood glucose monitoring. It is not recommend that CGM replace self-monitoring of blood glucose, but the intermittent application of CGM could be used to fine-tune glycemic control and assess patient compliance.[39,40,41] A large prospective study is needed to evaluate the clinical implications of this new monitoring technique.

When diet and exercise fail to maintain euglycemia, exogenous insulin is used.[42] According to the ACOG, insulin is required when the fasting plasma glucose is more than 95 mg/dl or when 1-h postprandial values are over the 130 to 140 mg/dl range and when 2-h postprandial values exceed 120 mg/dl.[37] Similarly, based on the 4th International Workshop - Conference on Gestational Diabetes, the ADA recommends maintaining a fasting plasma glucose below 95 mg/dl, with holding levels below 140 mg/dl 1-h postprandial and below 120 mg/dl 2-h postprandial.[5]

Some studies recommend starting insulin therapy when the fetal abdominal circumference (AC) measured by ultrasound is higher than the 75th percentile for gestational age.[43] The limitation of the use of AC as a measure for insulin initiation is that it is a snapshot information, whereas fetal growth is longitudinal. It should not be used as a single predictor, but in conjunction with GDM severity parameters and level of glycemic control throughout pregnancy.[1] Fetal macrosomia is related to maternal glucose levels, and in particular to 1-h postprandial glucose values.[38,44] A longitudinal study reveals a significant correlation between postprandial blood glucose levels and the growth of insulin-sensitive fetal tissues and, in particular, between 1-h postprandial blood glucose values and fetal AC.[45]

The glucose profiles of normal pregnant women without diabetes are based on two recent studies,[46,47] but the results of both studies imply that currently recommended normoglycemic criteria as targets for glycemic control in women with diabetes do not target the actual normal levels in nondiabetic women's pregnancies[1]: the fasting blood glucose level was 75 mg/dl and the postprandial peak glucose value level was 110 mg/dl. Glycemic profile in nondiabetic subjects provides a measure for the desired level of glycemic control in pregnancy that is complicated with diabetes mellitus.

Although paucity of information exists as regards the length of time that diet should be maintained before insulin initiation, one study suggests 2 weeks before adding insulin if the initial fasting plasma glucose level is 90 mg/dl or less.[47] In women with GDM with initial fasting values above 95 mg/dl, the results of diet therapy alone were less salutary.[37] When GDM is diagnosed after 30 to 33 weeks of gestation, and short time is available to achieve targeted glycemic control, pharmacologic therapy should be initiated.[1]

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