Pregnancy is a time of promise and expectation, but it can also raise the possibility for some women that they will develop gestational diabetes mellitus (GDM). Unlike other types of diabetes, gestational diabetes is not permanent. In most women, the condition disappears within a few days of delivery. GDM is a condition that develops during pregnancy, when the body is not able to make enough insulin to overcome the body’s resistance to insulin. The lack of insulin causes the women’s blood glucose level to become elevated compared to the usual levels seen during pregnancy. In Canada, GDM is higher than previously thought, varying from 3.7 percent in non-Aboriginal women to up to 18 percent in Aboriginal women.
GDM is caused by hormones that are released by the placenta, which in turn can change the way insulin works by blocking the interaction between insulin and glucose. These hormonal changes are a natural part of every pregnancy and usually don’t cause any maternal or fetal health problems. As the placenta grows, it produces more of these hormones, making it increasingly difficult for the body to use insulin, hence creating what’s known as insulin resistance. During this insulin resistance period, the pancreatic beta cells compensate by increasing their insulin production – usually up to three times as much insulin as normal. However, in some women, the pancreas cannot produce an adequate amount of insulin and therefore they will experience higher than normal glucose levels and in turn develop gestational diabetes. The extra blood glucose can also cross the maternal placenta and increase fetal blood glucose levels as well, which in turn will stimulate the fetal pancreas to produce more insulin to normalize fetal blood glucose levels. Some of this high glucose in turn will be converted and stored as fat in the fetus and impact fetal weight, contributing to macrosomis. Upon delivery however, as blood glucose levels normalize, the fetal pancreas will reduce its insulin production.
It is important to recognize and treat GDM promptly to minimize both fetal and maternal complications. In addition, it is important for women with a history of GDM to be screened after pregnancy due to an increased risk of developing type 2 diabetes after delivery, especially the first five years.
RIS K FACTORS FOR DEVELOPING GDM
Based on systematic review of several observational and a large cohort study, risk assessment for gestational diabetes should be done at first prenatal visit. Women with any of the following characteristics are at increased risk of being diagnosed with GDM, compared to women without these characteristics:
- Family history of diabetes, especially in first degree relatives (i.e. parent, sibling);
- Member of a high-risk population, including women of Aboriginal, Hispanic, South Asian, Asian and African descent;
- History of GDM in previous pregnancies;
- Personal history of abnormal glucose tolerance (also called “pre-diabetes”);
- Maternal age greater than or equal to 35;
- Maternal obesity (having a Body Mass Index (BMI) of 30 kg/m2 or higher);
- Previous delivery of a macrosomic infant (birth weight greater than 4.1 kilograms or nine pounds);
- History of Polycystic Ovary Syndrome (PCOS)
- Having Acanthosis Nigricans (a skin disorder characterized by the appearance of darkened patches of skin);
- Use of corticosteroids.
Risks of GDM to infant
By the time gestational diabetes is detected, the fetus is fully formed but still actively growing. This makes the infant vulnerable to the risks associated with untreated diabetes. The fetus may have:
- Increased risk of preterm delivery;
- Macrosomia (large-for-gestational-age infant weighing >4,000 grams);
- Shoulder dystocia;
- Neonatal hypoglycemia (low blood sugar levels after birth);
- Neonatal hyperinsulinemia (excess levels of insulin in the blood);
- Prolonged newborn jaundice (slightly yellow skin colour) due to the build-up of body chemicals called bilirubin;
- Prolonged hyperbilirubinemia;
- Respiratory distress syndrome;
- Increased risk for potential future obesity, glucose intolerance and type 2 diabetes in adolescence and early adulthood.
Risks of GDM to mother
- Increased odds of preterm delivery;
- Increased risk of birth trauma due to large-forgestational-age (LGA) infant;
- Possibility of Cesarean delivery (C-section);
- Increased risk of infection (i.e. vaginal and bladder);
- Higher incidence of development of preeclampsia or toxemia (high blood pressure, swelling and presence of protein in the urine);
- Risk of developing type 2 diabetes. Up to 20 percent of women will develop type 2 diabetes after nine years and up to 60 percent in the following 10 years;
- Cardiovascular disease (CVD) due to increased prevalence of metabolic syndrome in GDM.
Other risk factors as outlined in several international studies include:
- Lower family income;
- Vitamin D deficiency during pregnancy;
- Sleep-disordered breathing in pregnant women;
- High blood pressure before and during pregnancy;
- Women with cystic fibrosis;
- Higher C-peptide levels and lower insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels at 13 weeks gestational;
- Twin pregnancy.
Given the controversy that persists in the international community about the screening and diagnosis of GDM, there is no clear answer to what is ideal. Based on the outcome of the 2008 HAPO study, a prospective observational study, and several other largescale, prospective, observational studies, the 2019 Diabetes Association Clinical Practice Guidelines expert committee have modified its diagnostic criteria for GDM in their new 2019 guidelines. Since hyperglycemia during pregnancy was associated with an increased risk of maternal and/or fetal complications, the most common method of screening in Canada recommended by the CDA expert committee is the sequential two-stage screening approach: a 50-gram oral glucose challenge test (OGCT) performed between 24 and 28 weeks of gestation, followed by a 75-gram oral glucose tolerance test (OGTT) as the diagnostic test if a certain threshold has surpassed.
However, for women with multiple risk factors, this screening test should be offered at any stage in the pregnancy.
The preferred approach consists of a 50-gram glucose drink given any time of the day (non-fasting state), followed by a one-hour plasma glucose (PG) test. If the one-hour PG test is:
- Less than 7.8 mmol/L, no presence of GDM. Reassess at 24-28 weeks if tested earlier or if multiple risk factors for GDM are present.
- Between 7.8 mmol/L and 11 mmol/L, a positive screen is indicated. Then an Oral Glucose Tolerance Test (OGTT) is needed, consisting of 75 grams of glucose drink. Blood glucose measures are taken at fasting, one hour and two hours after. If one value is met or exceeded, GDM diagnosis is established:
- FPG ≥ 5.3mmol/L
- 1h PG ≥ 10.6 mmol/L
- 2h PG ≥ 9.0 mmol/L
- 11.1 mmol/L or larger, GDM diagnosis is confirmed and no further testing needed.
An alternative one-step approach proposed by the International Association of Diabetes and Pregnancy Study Groups may be used to screen and diagnose GDM. Patients are required to consume a 75-gram glucose drink, with no prior screening with the 50 gram GCT. If one of the followign values is met or exceeded, GDM diagnosis is confirmed:
- Fasting Plasma Glucose (FPG) ≥ 5.1 mmol/L
- 1h PG ≥ 10.0 mmol/L
- 2h PG ≥ 8.5 mmol/L
Upon diagnosis with GDM, care by an interdisciplinary healthcare team composed of registered nurses (RN), registered dietitians (RD) and endocrinologists along side the obstetrician/gynecologist is recommended for all women with GDM throughout the remainder of their pregnancies. These professionals will evaluate, assess and follow up with every GDM patient until delivery and several weeks postpartum. The patients will receive instructions regarding monitoring urinary ketones, self monitoring blood glucose (SMBG), insulin (if needed), diet and exercise from this healthcare team.
Although the diagnosis should be taken seriously, GDM can be managed by some of the same measures with which all types of diabetes are managed. The goal of therapy for women with GDM is to normalize the maternal metabolic setting to result in a normal, healthy infant. Therapeutic decisions should be designed to decrease both maternal and fetal morbidity and mortality.
Usual management includes a combination of monitoring urinary ketones and blood glucose, as well as lifestyle interventions such as dietary changes and exercise (unless obstetrical contraindications exist or glycemic control is worsened by the activity). In some cases, daily insulin injections will be necessary.
To help motivate and empower patients, diabetes education and nutrition counselling should be sensitive to cultural preferences and special patient needs. Written material in multiple languages should be available for patients, including menu ideas and food choices that best match their individual food habits and ethnic background.
Let’s look at each treatment modality in more details.
Urinary ketone monitoring
Women with GDM, in an effort to control their glucose by diet, may put themselves and their baby at risk for starvation ketosis. Older studies raised the possibility that elevated ketoacids may have detrimental effects on the fetus. While clinical significance of these findings are doubtful, it appears wise to check for urine ketones daily. Therefore, most Diabetes Education Centres recommend testing for ketones in the urine first thing in the morning after a long period of fasting overnight. A positive ketone test is a result of breakdown of body fat stores. This usually happens if there is insufficient calorie or carbohydrate intake, long periods without food between meals or snacks, or not enough insulin. If this happens there is a need to adjust the meal plan and/or increase bedtime insulin dose. If however it is always negative, one may decrease the frequency of testing to one to two times per week. Patients are encouraged to call the registered dietitian and/or the nurse educator if ketone test results show greater than trace amounts of ketones.
Self Monitoring of Blood Glucose
SMBG is essential in women with gestational diabetes. Both fasting and post-meal testing are recommended to guide therapy in order to achieve glycemic targets. Suggested blood glucose monitoring includes fasting plasma glucose, one- or two-hour post meals and at bedtime, usually four to five times a day. Due to the increased risk of nocturnal hypoglycemia during pregnancy, testing during the night is often necessary in patients receiving insulin. Recommended blood glucose and glycated hemoglobin (A1C) levels during pregnancy are considered lower than in nonpregnant adults. Target values are:
- Fasting plasma glucose (FPG) < 5.3 mmol/L
- One-hour postprandial PG <7.8 mmol/L
- Two-hour postprandial PG <6.7 mmol/L
If glucose levels are consistently elevated, treatment with insulin is usually recommended. If however, blood glucose levels are consistently within target, the frequency of testing can sometimes be decreased.
Cardiovascular conditioning appears to improve glycemic control primarily from increased tissue sensitivity to insulin. As a result both fasting and postprandial blood glucose concentration can be reduced and, in some women with GDM, the need for insulin may be obviated. Therefore, physical activity is encouraged as an addition to nutrition therapy unless obstetrical contraindications exist or glycemic control is worsened by the activity. The frequency, amount and type of exercise however, need to be addressed on an individual basis.
The 2013 Clinical Practice Guidelines promote moderate level of activity most days of the week as part of the treatment plan. Taking a 20- to 30-minute walk after meals can help lower blood glucose levels. Many women find that a walk after breakfast is especially helpful, while others need to walk after each meal. Other good exercise choices include swimming, yoga and prenatal stretching classes.
Very intense exercise activities are not generally recommended during pregnancy because they can cause a rise in blood glucose. These include jogging, tennis, racquetball, volleyball and water skiing. Also it is not recommended to exercise for a long period of time.
Multiple, short exercise sessions lasting at least 10 minutes each in the course of the day should be considered.
Nutrition therapy is an integral part of the management of GDM. Every woman with GDM should be evaluated and followed by a registered dietitian to ensure that nutrition therapy promotes normal levels of blood glucose, appropriate weight gain and adequate nutritional intake. Although overall nutrition requirements during pregnancy are similar for women with or without diabetes, specific nutrition management for women with GDM consists of the following:
Weight gain. Recommendations for weight gain in GDM are currently similar to national guidelines in healthy women, and vary somewhat from country to country. In Canada, readers should refer to Health Canada guidelines, “Nutrition for a Healthy Pregnancy”. The 2010 guidelines for weight gain during pregnancy vary by pre-pregnancy BMI and are at right. Inadequate weight gain during pregnancy increases risk of having a low birth weight baby (<2,500 grams) and with excessive weight gain, there is a risk of having a large-for-gestational-age baby (>4,000 grams). Weight should be checked at each visit. The dietitian should review food intake with the patient at clinic visits. Unexpected weight gain or loss may indicate a need for further diet review or revision of the meal plan. Patients may inappropriately restrict food intake to levels less than recommended on their meal plan in an effort to control post meal blood glucose values and avoid insulin therapy.
Energy intake should take into consideration pre-gravid BMI. Calorie requirements are calculated from the Harris Benedict Equation and are based on ideal body weight. General daily calorie requirements in women with normal pre-gravid body weight range between 1,800 to 1,900 calories a day in the first trimester, with energy needs increasing during the second and third trimesters for optimal fetal growth, being 340 to 452 extra calories more a day. Hypocaloric diets are not recommended as they may result in maternal weight loss, starvation ketosis and poor intake of nutrients such as protein and calcium. However, energy intake for overweight or obese women may be slightly restricted as long as the rate of weight gain is appropriate and provided ketosis is avoided. Ketones should be monitored to verify that adequate calories are provided to prevent ketone formation as recommended in the CDA Clinical Practice Guidelines.
Amount and distribution of carbohydrate in the diet should be individualized based on clinical parameters such as gestational weight gain, blood glucose levels, ketones and level of serum triglycerides. It is generally recommended:
- Total carbohydrates comprise 45 to 50 percent, but up to 60 percent of total energy may be acceptable for pregnancy and provide no fewer than 175 grams of carbohydrate a day to prevent ketosis. Expectations to these recommendations may be made based on individual nutrition prescription, personal preferences and glycemic response. Carbohydrates should primarily be coming from slow-released carbohydrate sources (low to medium glycemic index) which raise post-meal blood glucose concentrations less than simple carbohydrate or high glycemic index types. Slowly released carbohydrates include whole grain products (breads, pita, tortilla, cereals, pasta), brown rice, quinoa or barley; starchy vegetables (new or white potato, yam/sweet potato, corn); most fruits; milk and alternatives (lower fat milk, yogurt, kefir, soy/rice/almond milk). The remaining calories should be divided between protein and fat.
- Simple sugars are best to avoid or limit. They include sugar (white, brown), honey, syrup, molasses, jam, jelly, marmalade, sweets/hard candy, jello, fruit juice, regular pop, regular tonic water. Refined flour products, pasta and white rice also belong in this category. These foods provide sweetness and calories, but few nutrients. Excess sugar can contribute to excess calories and can raise blood sugar levels quickly in people with diabetes.
- Consumption of the following non-nutritive sweeteners during pregnancy and while lactating are acceptable: Acesulfame Potassium (Acyl-K), Aspartame (Equal, Nutrasweet), Sucralose (Splenda), Steviol Glycosides (Stevia), Saccharin and sugar alcohols (xylitol, mannitol and sorbitol), but they should be consumed in moderation to not replace more nutritious food and fluid choices. Cyclamate is not recommended during pregnancy.
- Carbohydrate is recommended to be distributed throughout the day over three meals plus two to three snacks, one of which can be an evening snack, which may prevent overnight ketone formation. Expectant moms should not go more than four waking hours without eating. The amount of carbohydrate at breakfast may need to be limited if morning glucose intolerance is present. A general guideline is 15 to 45 grams (one to three servings) of carbohydrate sources of food at breakfast and 45 to 60 grams (three to four servings) at lunch and dinner. Snacks would generally consist of 15 grams of carbohydrate during the day and 15 to 30 grams at bedtime. This should comprise 175 grams of carbs in total. A protein-containing food may accompany the day snacks, but is strongly recommended at bedtime. The carbohydrate regimen may require adjustment if insulin therapy is initiated. More information on serving sizes and food groups is available in Eating Well with Canada’s Food Guide (healthcanada.gc.ca/foodguide) as well as on the nutrition facts tables that appear on all packaged food.
Protein intake recommendations are similar to that of non-pregnant women, recommending 1.1g/kg/day or an additional 25 g/day to meet increased needs during pregnancy. Vegetarian and vegan patients should be offered plantbased protein choices and should consider the carbohydrate content of these foods.
Fat can comprise up to 40 percent of total energy intake during pregnancy. Women should be advised to follow the nutrition recommendations for general health by consuming a diet low in saturated fat, trans fat and cholesterol. This can be achieved by reading food labels, choosing leaner meats and dairy products as well as using lower fat cooking methods.
Requirements of energy, protein and many nutrients will be further increased in adolescent and multiple pregnancies.
Women with GDM should take a daily multivitamin containing 0.4 to 1.0 mg (400 to 1,000 mcg) folic acid to reduce the risk of congenital abnormalities and 16 to 20 gram iron.
Individualized meal and snack plans should take into consideration food availability, literacy, cultural preferences and lifestyle. A diet history will allow the dietitian to assess current eating patterns and food preferences. Counselling may be provided as needed for other therapeutic diet issues including heartburn, hyperemesis or food allergies/ intolerances. Referral to community programs may be appropriate if food availability is an issue.
If women with GDM do not reach the recommended blood glucose target levels within two weeks of nutrition therapy alone, insulin therapy may be initiated. The use of insulin to achieve glycemic targets has been shown to reduce fetal and maternal morbidities. Certain types of insulin can be safely used during pregnancy. Dose and frequency of insulin injection depends upon blood glucose levels, may start with once daily injection at bedtime. The insulin choice is usually either an intermediate acting (NPH) or a long acting, basal analogue detemir (Levemir) or glargine (Lantus). If post-meal blood glucose levels remain elevated, up to four injections a day are usually recommended. Post meal insulin choice includes rapid-acting bolus analogue aspart (Novorapid) or lispro (Humalog) over regular insulin, taken before meals, although perinatal outcomes are similar. All these insulins have enough research to support their safety during pregnancy. Insulin requirements increase with the progression of pregnancy. Education on insulin therapy is generally conducted by a Diabetes Educator, and injection techniques should be reviewed at each visit, as well as how food affects blood glucose and pattern management.
Oral antihyperglycemic agents
Glyburide or metformin may be used for glycemic control in women who are nonadherent or refuse to take insulin. Use of oral agent in pregnancy is off-label and should be discussed with the patient.
In addition to the above mentioned management tools, assessment of the GDM patient’s emotional and psychosocial states are also important and consideration should be given to professional referrals as needed.
Women who have had GDM are at increased risk of developing type 2 diabetes later in life by up to 12 fold, the highest prevalence being usually in the first five to 10 years postpartum. Therefore screening with a 75 g OGTT (twohour) should be done between six weeks and six months postpartum to rule out diabetes, prediabetes or undiagnosed type 1 or type 2 diabetes during pregnancy.
To reduce the risk of developing type 2 diabetes, Impaired Glucose Tolerance (IGT) or metabolic syndrome in the future, women with previous GDM should:
- Be encouraged to breastfeed for at least three months postpartum in order to reduce offspring obesity, especially in the setting of maternal obesity;
- Follow a healthy lifestyle that includes healthy eating to meet daily need of nutrients, vitamins and minerals for breastfeeding and regular physical activity;
- Strive to reach a healthy BMI of 18.5 to 25 kg/m2;
- Be screened regularly for the development of type 2 diabetes or prediabetes;
- Consult their physician and be screened for type 2 diabetes when planning another pregnancy.
With prompt diagnosis and good management, women with GDM can expect to have a healthy pregnancy and a happy, healthy baby.