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parag

Dr. Parag Biniwale

Pune
Chairperson, Young Talent Promotion Committee, FOGSI
E-mail: paragbin@hotmail.com / sauravakshay@yahoo.com

Gestational diabetes mellitus (GDM) is a common disorder affecting ~ 7% of pregnancies each year. It is on the rise in our population, the rise is attributed to our dietary pattern & lifestyle.

GDM is characterized by carbohydrate intolerance that begins or is first diagnosed during pregnancy. Some researchers are recommending universal screening of all pregnant women during pregnancy; however, the American Diabetes Association (ADA) recommends screening of only moderate- and high-risk pregnancies. Early diagnosis & management of GDM helps in reducing maternal and fetal complications. Patients with GDM are at higher risk for excessive weight gain, preeclampsia, and having cesarean delivery. Babies of mothers with GDM are at higher risk for macrosomia, birth trauma, and shoulder dystocia. After delivery, these infants have a higher risk of developing metabolic derangement (hypoglycemia, hypocalcemia, hyperbilirubinemia), respiratory distress syndrome, polycythemia. These babies are at risk of being obese and suffer from type 2 diabetes.

Screening

For many years, screening for GDM was only by taking patients’ history. The first concept of biochemical screening was introduced by Mahan and O’Sullivan. They proposed using the 1-hour 50-g oral Glucose Challenge Test (GCT) for screening. Risk factors for GDM include being overweight before pregnancy (BMI > 25kg/m2), having a first-degree relative with diabetes, previous H/O GDM, previous macrosomia or large-for gestational- age baby, polycystic ovarian syndrome, age > 25 years. Multiparous women have a very high prevalence of GDM (~ 13%) as compared to primigravida. At patients’ first antenatal visit, providers should assess which category patients fit best. For normal-risk patients, it is widely recommended to screen with a nonfasting, 1-hour, 50-g GCT at 24–28 weeks’ gestation. Cosson et al performed an observational study comparing universal screening versus selective screening for GDM. They found that the universally screened group had more favourable outcomes. Williams et al. studied 25,118 deliveries to find out prevalence of GDM in low risk population. They found that ~ 10–11% of women who delivered would never have been screened for GDM, and they were missing 4% of women with GDM.

For higher-risk patients, screening is warranted earlier in pregnancy. Patients with symptoms of polyphagia, polyuria and polydypsia, may be diagnosed with a random blood glucose test result >_ 200 mg/dl. Screening with a fasting blood glucose test has been shown to have a sensitivity of 70–90% and a specificity of 50–75%10 and is therefore not considered an adequate screening method. It is observed that a single fasting glucose screen failed to identify 60% of women with abnormal 2-hour blood glucose levels. Metzger et al. found that a 1-hour 50-g GCT value >_ 140 mg/dl would have an ~ 80% sensitivity and a proportion of women with a positive test of 14–18%. Using a cut off value of >_ 130 mg/dl increases sensitivity to ~ 90%. A positive test requires further diagnostic testing.

Diagnosis

When diagnosing GDM, clinicians must keep in mind that patients may in fact have 1) undiagnosed type 2 diabetes, 2) mild abnormal glucose tolerance before pregnancy that worsens in pregnancy because of increased insulin resistance, 3) normal glucose tolerance before after an overnight fast of at least 8 hours but not more than 14 hours and after at least 3 days of unrestricted diet including >_150 g of carbohydrate per day. If using the 100-g OGTT, the cutoff values should be fasting < 95 mg/dl, 1- hour >_ 180 mg/dl, 2-hour >_ 155 mg/dl and 3-hour > 140 mg/dl .Two or more abnormal values must be measured for the test to be considered a positive diagnostic test. When using the 2-hour 75-g OGTT, the cutoffs are the same at 1 and 2 hours. Two or more abnormal values indicate diagnosis of GDM. However, studies have shown that mothers with only one abnormal value are at increased risk for macrosomic infants and other morbidities.

Maternal and Fetal Complications

Maternal complications. Women with GDM are more prone to develop hypertensive disorders and preeclampsia. They have moderate to high risk of nongestational diabetes in the first several years postpartum. This risk is particularly high in women with marked hyperglycemia, obesity, and a diagnosis of GDM earlier than 24 weeks gestation. They are more likely to have operative delivery; caesarean or operative vaginal delivery.

Fetal complications. Fetuses born to mothers with GDM have higher risks of developing macrosomia, hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, polycythemia, hypertrophic cardiomyopathy, and hypocalcemia, and these complications have been reported with varying frequency. Macrosomia is the most common morbidity, occurring in 15–45% of infants exposed to hyperglycemia. This occurs when excess glucose is transferred to the fetus as a result of maternal hyperglycemia resulting in fetal hyperinsulinemia, which is responsible for increased growth. Other maternal factors like fetal macrosomia include obesity and high concentrations of lipids and amino acids. In subjects with preexisting diabetes, 1-hour postprandial glucose levels were more predictive of fetal Macrosomia than were fasting values. Not only are there immediate risks to the fetus, but infants exposed to maternal diabetes in utero have an increased risk of diabetes and obesity in childhood and adulthood.

Treatment

Diet and exercise. The first line of management of GDM is changes in dietary habits & exercise. Patients benefit significantly by receiving dietary counselling to plan meals & thus learn to count carbohydrates. The ADA recommends that women of normal weight in the second half of pregnancy consume 30–32 kcal/kg body wt. Carbohydrate intake should be ~ 40% of total calories and should be selected from carbohydrate foods with a low glycemic index. In overweight women, this requirement should be reduced to 25 kcal/kg. Excessive calorie restriction can be monitored by checking for fasting ketonuria, especially when there is a caloric restriction > 30%.

Insulin. For years, human insulins were the only insulin options available for the treatment of GDM. The recent advent of newer insulin analogs that mimic physiological insulin action calls for more information regarding the safety and applicability of their use in GDM. The insulin analogs lispro and aspart have proven to be more effective than regular human insulin in achieving goal glucose levels and reducing the risk of fetal macrosomia. Using analogs has the advantage of dosing 5–10 minutes before meals, versus 30–45 minutes insulin and has been found to be as effective as insulin therapy for GDM treatment. Langer et al. found that glyburide was as effective as insulin for the treatment of GDM in 404 patients, despite severity of disease when fasting plasma glucose on a glucose tolerance test was between 95 and 139 mg/dl. More than 80% of GDM patients were found to achieve the established levels of control with glyburide; 71% of patients required an average dose of 10 mg of glyburide daily. There was no significant difference in neonatal birth weight, metabolic complications, and composite outcome between the two groups. Markers for advancement to insulin include inadequate glycemic control, severe restriction of carbohydrates and calories necessary to meet glycemia goals, and a fetus that is large for gestational age. Glyburide is contraindicated in those with an allergy to sulfa. The main risk of taking glyburide, as with insulin, is hypoglycemia.

Metformin. The biguanide metformin during pregnancy has mostly been studied in the first 12 weeks of gestation for patients with polycystic ovary syndrome (PCOS). Preliminary studies have shown that in women with PCOS, metformin may be safe and may reduce risk of miscarriage and development of GDM when used for the entire pregnancy. Metformin may also have a role in therapy forGDM; a multicenter trial is underway in New Zealand to address this question.

Managing delivery A policy of induction of labour at 38 weeks of gestation in diabetic women treated with insulin was associated with a reduction in the frequency of birth weight above 4000 g and above the 90th percentile. This intervention did not appear to increase the risk of caesarean section. Neonatal morbidity was rare and similar between groups. However, only one randomized controlled trial was conducted to assess this intervention. Fifty percent of women in the expectant management group had labour induction for various obstetric indications. This decreases the power of the study to show differences between groups. Only 13 women with pregestational diabetes were included. Therefore, no conclusion can be generalised to this sub-group of women.

Postpartum follow-up. Maternal insulin requirements drop markedly in the postpartum period. Because patients with GDM have a high risk of developing type 2 diabetes, it is important to continue screening these patients. After child birth, Patients should attempt to minimize insulin resistance through exercise, maintenance of normal weight, and avoidance of drugs that induce insulin resistance. The ADA has recommended an annual fasting blood glucose test, a 6-week postpartum 75-g 2-hour OGTT, and contraception to ensure that patients will not conceive in the face of marked hyperglycemia, which could lead to increased congenital malformations. Patients who had GDM in a previous pregnancy have a 33–50% likelihood of recurrence in a subsequent pregnancy. Given the well-known sequelae of diabetes, which include macro- and microvascular disease and cardiovascular disease, it is important to recognize the risk and prevent the development of diabetes in the future in women with GDM. In the Diabetes Prevention Program, intensive lifestyle modification to promote weight loss and increase physical activity resulted in a 58% reduction in the relative risk of type 2 diabetes in adults with impaired glucose tolerance. In another study with 1,079 participants aged 25–84 years, weight loss was the dominant predictor of reduced diabetes risk. Every kilogram of weight loss resulted in a 16% reduction in risk.

Summary

GDM is associated with a number of fetal and maternal complications especially if glucose levels are uncontrolled. Diagnosing women with GDM early through screening at appropriate gestational age is crucial to avoiding unfavourable outcomes. Several drugs that are both effective and safe are being used to treat women with GDM if diet and exercise fail; these include human insulin, insulin analogs, and glyburide. Studies are underway to test the safety and efficacy of metformin in pregnancy. Women with GDM should be followed postpartum and monitored for type 2 diabetes to reduce the risks for complications of diabetes. Suitable contraceptives should be recommended to the couple so that immediate conception is avoided.

Suggested reading

  1. American Diabetes Association: Gestational diabetes mellitus (Position Statement). Diabetes Care 23 (Suppl. 1):S77–S79, 2000
  2. Elective delivery in diabetic pregnant women, The Cochrane Library 2009, Issue 3
  3. Metzger BE, Coustan DM, Organizing Committee: Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 21 (Suppl. 2):B161–B167, 1998
  4. National Collaborating Centre for Women’s and Children’s Health: Antenatal Care: Routine Care for the Healthy Pregnant Woman. London, Royal College of Obstetricians and Gynaecology, 1993
  5. American Diabetes Association: Gestational diabetes mellitus (Position Statement). Diabetes Care 29 (Suppl. 1):S88–S90, 2004