Treatment and Prevention of Gestational Diabetes Mellitus

The goal of medical management of women with gestational diabetes mellitus (GDM) is to prevent maternal and fetal diabetic complications. By normalizing the level of glycemia and other metabolites (lipids and amino acids), perinatal mortality and morbidity can be prevented. Patients diagnosed with GDM should monitor their blood glucose levels, exercise, and undergo nutrition counseling in order to maintain normoglycemia. Maternal surveillance should include blood pressure and urine protein monitoring to detect hypertensive disorders. If patients cannot maintain their glucose levels with dietary changes, insulin therapy should be introduced. If diabetes is controlled, there is no need to pursue delivery before 38 weeks of gestation. In patients who have comorbid conditions or who require insulin, antenatal screening with nonstress tests and an amniotic fluid index should be initiated at 32 weeks of gestation.[1,2]

Blood glucose monitoring

The accepted treatment goal for GDM is to maintain a fasting plasma glucose level ≤105 mg/dL (5.8 mmol/L). The postprandial plasma glucose level should be ≤155 mg/dL (8.6 mmol/L) at 1 hour and ≤130 mg/dL (7.2 mmol/L) at 2 hours. Postprandial testing is preferred to preprandial glucose testing.[1] Daily self-monitoring of blood glucose levels is recommended (minimum 4 times a day).[1,2]

Medical nutrition therapy

Nutritional counseling is the mainstay of therapy. The optimal dietary prescription would be the one that provides the calories and nutrients necessary for maternal and fetal health, resulting in normoglycemia and appropriate weight gain and preventing ketosis. The American Diabetes Association (ADA) recommends restriction of carbohydrates to 35% to 40% of daily calories, protein to 20% to 25%, and fat to 30% to 35%. Complex carbohydrates are preferred, as simple carbohydrates tend to produce postprandial hyperglycemia. Carbohydrate intake should be minimal at breakfast. Hypercortisolemia that occurs early in the morning in normal pregnant women increases insulin resistance. Once cortisol levels decrease, carbohydrate intake can increase. The ADA diet provides 30 Kcal/kg for nonobese women (body mass index [BMI] 20 to 26). If BMI is greater than 30, the ADA suggests lowering the daily caloric intake by 30% to 33%.[1-4] Caloric intake should be spaced evenly throughout the day as shown in Table 1.[3] Sweeteners should be used cautiously. The Food and Drug Administration (FDA) and the ADA have approved the use of the following low-calorie sweeteners: aspartame (Nutrasweet®), acesulfame (Sweet One®), and sucralose (Splenda®).[5]

Table 1. Distribution of calories in a diabetic diet[3]

A Cochrane review found no difference in the prevalence of birth weights greater than 4,000 g (8 lb, 13 oz) or caesarean deliveries in women with GDM who randomly received primary dietary therapy or no specific treatment and concluded that insufficient evidence exists to recommend only dietary therapy.[1,6]

Exercise therapy

Exercise depends on prior activity. Regular exercise may be useful in the treatment and prevention of GDM. Cardiovascular conditioning (aerobic exercise) has both acute and long-term effects on insulin sensitivity, insulin secretion, and glucose metabolism. Exercise training with weight control or weight reduction is associated with lower fasting and postprandial insulin concentrations and apparent increases in insulin sensitivity.[1,2,3,7,8]

Insulin therapy

Prospective trials involving insulin therapy in patients with GDM have shown a reduction in the incidence of neonatal macrosomia. To identify the women who will require insulin, circulating glucose levels should be monitored at frequent intervals. The ADA and the American College of Obstetricians and Gynecologists (ACOG) recommend glucose measurements be taken both fasting and after meals at 1- to 2-week intervals. Insulin therapy should be initiated if fasting glucose levels exceed 105 mg/dL and/or if the 2-hour postprandial levels exceed 120 mg/dL on 2 or more occasions within a 2-week interval.[1] ACOG recommends a more conservative goal of a fasting capillary blood glucose level below 95 mg/dL (5.3 mmol/L).[1,9]

There are no definite studies regarding the superiority of one type of insulin or regimen on the perinatal outcome. The simplest regimen that will control the blood glucose level is generally recommended. Collaborative care with an obstetrician or perinatologist is indicated. Insulin dosage usually increases as the pregnancy progresses and insulin resistance increases. Typically, the initial dosage is 0.7 units per kg per day; a regimen of one dose consisting of two thirds of the total amount given in the morning and one dose consisting of one third of the total amount given in the evening is preferred. One third of each dose is given as regular insulin, and the remaining two thirds as NPH (neutral protamine Hagedorn) insulin.[1] ADA recommends the use of human insulin, as the use of insulin analogs has not been adequately tested in GDM.[2]

Oral hypoglycemic agents

Use of these agents to treat GDM is not recommended, due to concerns about potential teratogenicity and prolonged neonatal hypoglycemia. Recent evidence shows that glyburide does not enter the fetal circulation, but additional trials are necessary to support its safety and effectiveness.[1,2]

In a prospective study of patients with polycystic ovary syndrome, metformin therapy has been shown to decrease the incidence of GDM, reduce insulin resistance and insulin secretion, reduce first-trimester miscarriage rates, and result in no apparent increase in congenital anomalies. Further studies are needed to demonstrate the safety and effectiveness of metformin (Glucophage®) in pregnancy.[1,10]

Obstetric management

Antepartum care

Surveillance for fetal well-being should begin between 28 and 32 weeks. Fetal surveillance methods may include ultrasound, fetal kick counts, the nonstress test (NST), the contraction stress test (CST), and the biophysical profile. The frequency and timing of fetal surveillance may depend on the severity of the disease and the degree of glycemic control.[1,3,11]

Intrapartum and postpartum management

Induction of labor is recommended at 38 weeks in patients with poor glucose control and macrosomia. The possibility of shoulder dystocia in a macrosomic infant must be considered, and caesarean section may be indicated to avoid the trauma of delivering a large infant (>4,000 g). Patients with diet-controlled diabetes need to have their glucose levels checked on admission to labor and delivery. For patients on insulin who are in active labor, the capillary blood glucose levels should be monitored hourly. Target values are 80 to 110 mg/dL (4.4 to 6.1 mmol/L).[11]

Women with GDM rarely require insulin in the postpartum period but should be screened for diabetes 6 weeks after delivery and then annually.[1] Patients should be encouraged to breastfeed, as it improves glycemic control.[2]

Long-term considerations

Contraception should be discussed, as these patients are likely to have the same condition in subsequent pregnancies and are at an increased risk of developing type 2 diabetes in the future. Low-dose estrogen-progestogen oral contraceptives may be used in women with prior histories of GDM, as long as no medical contraindications exist. Children of women with GDM should be followed for the development of obesity and/or abnormal glucose tolerance. Medications that worsen insulin resistance (eg, glucocorticoids, nicotinic acid) should be avoided if possible.[1,2]

Prevention

An awareness of risk factors and prenatal screening at 24 to 28 weeks of pregnancy can lead to early detection of gestational diabetes. As there is an increased risk of fetal and neonatal death with gestational diabetes, this risk can be lowered with effective treatment and surveillance of the mother and fetus.

Women who have had GDM should be provided with health education on reducing cardiovascular risk factors. The importance of weight maintenance and exercise should be stressed. Regular follow-up would allow diabetes to be diagnosed earlier, and this should result in earlier treatment and reduction of complications.[12]

Many women who have GDM go on to develop type 2 diabetes years later. Certain basic lifestyle changes may help prevent diabetes after gestational diabetes. In a study that presented an economic model of the health care dollars that could be saved by promoting postpartum lifestyle changes in women diagnosed with GDM, it was postulated that $32, $140, or $331 million could be saved over 10 years assuming the incidence of diabetes could be reduced by 10%, 25%, or 50%, respectively.[13,14] Lifestyle changes include weight reduction and physical activity.[13]

Weight reduction

If patients are more than 20% over their ideal body weight, losing even a few pounds can help avoid developing type 2 diabetes. Watching portion size, limiting fat intake to 30% or less, and healthy eating habits can go a long way in preventing diabetes and other health problems.

Physical activity

Regular physical activity allows the body to use glucose without extra insulin, thus combating insulin resistance. Before starting an exercise program, it is advisable to check with the doctor.

Two recent large studies have shown that decreasing insulin resistance through diet, physical activity, or metformin can decrease the development of diabetes in individuals at high risk.[15]

According to an ADA-funded study, it might be possible to determine who is at risk for GDM before it actually develops, by looking for a marker in the blood. Early research in a small number of women indicates that low levels of proteins (sex hormone binding globulin [SHBG]) early in pregnancy are related to increased risk of GDM. A larger study is being conducted as an ongoing research program at the Harvard Medical School to determine if women who have low levels of SHBG at about 12 weeks go on to develop GDM. If so, SHBG could be a predictor, and early intervention can be started.[16]

References

1. Turok DK, Ratcliffe SD, Baxley EG. Management of gestational diabetes mellitus. Am Fam Physician. 2003;68:1767-1772.
2. ADA. Gestational diabetes mellitus. Diabetes Care. 2004;27(suppl 1):S88-S90.
3. Vidaeff AC, Yeomans ER, Ramin SM.Gestational diabetes: a field of controversy. Obstet Gynecol Surv. 2003;58:759-769.
4. Tamas, G, Kerenyi Z. Gestational diabetes: current aspects on pathogenesis and treatment. Exp Clin Endocrinol Diabetes. 2001;109(suppl 2):S400-S411.
5. ADA website. Sweeteners & desserts. Available at: http://www.diabetes.org/nutrition-and-recipes/nutrition/sweeteners.jsp. Accessed June 28, 2004.
6. Walkinshaw SA. Dietary regulation for 'gestational diabetes'. Cochrane Database Syst Rev. 2000;(2):CD000070.
7. Diet and exercise in noninsulin-dependent diabetes mellitus. NIH Consensus Statement Online 1986. Dec 8-10;6:1-21.
8. ADA. Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl 1):S4-S36.
9. American College of Obstetricians and Gynecologists Committee on Practice Bulletins - Obstetrics. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 30, September 2001 (replaces Technical Bulletin Number 200, December 1994). Gestational diabetes. Obstet Gynecol. 2001;98:525-538.
10. Glueck CJ, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril. 2002;77:520-525.
11. Siccardi DC. Gestational diabetes. Available at: http://www.medstudents.com.br/ginob/ginob4.htm. Accessed October 25, 2004.
12. Girling J, Dornhorst A. Pregnancy and diabetes mellitus. In: Pickup JC, Williams G, eds. Textbook of Diabetes 2. 3rd ed. Malden, Ma: Blackwell Science; 2003:65.1-65.39.
13. Carr DB, Gabbe S. Gestational diabetes: detection, management, and implications. Clin Diabetes. 1998;16:4-11.
14. Gregory KD, Kjos SL, Peters RK. Cost of non-insulin-dependent diabetes in women with a history of gestational diabetes: implications for prevention. Obstet Gynecol. 1993;81:782-786.
15. Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with type 2 diabetes. Diabet Med. 2004;21:103-113.
16. ADA. Diabetes forecast January 2004. Available at: http://www.diabetes.org/diabetes-forecast/jan2004/research.jsp. Accessed June 28, 2004.