Gestational diabetes mellitus: Practice guidelines

Jiji Elizabeth Mathews; RN Preethi; HS Asha

doi:10.4103/cmi.cmi_64_17

PRACTICE GUIDELINES

Year : 2017 | Volume : 15 | Issue : 3 | Page : 216-221

Gestational diabetes mellitus: Practice guidelines

Jiji Elizabeth Mathews¹, RN Preethi², HS Asha²
¹ Department of Obstetrics and Gynaecology, Christian Medical College, Vellore, Tamil Nadu, India
² Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India

Date of Web Publication

7-Aug-2017

Correspondence Address:
Jiji Elizabeth Mathews
Department of Obstetrics and Gynaecology, Christian Medical College, Vellore - 632 004, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/cmi.cmi_64_17

Abstract

Gestational diabetes melliturs is defined as carbohydrate intolerance of varying severity, detected for the first time in pregnancy. Since the Indian population is at moderate to high risk, screening is recommended for all pregnant women. Peri-conceptional glycemic control is the hallmark of optimal management of pregestational diabetes. 80% of the women with gestational diabetes can be treated with MNT and only 20% need additional therapy. Of the women requiring additional therapy, only 25% need insulin therapy. Oral hypoglycemic agents have been shown to be comparable with insulin in treating women with moderate gestational diabetes and can be safely used.

Keywords: Congenital anomalies, maternal complications, neonatal complications

How to cite this article:
Mathews JE, Preethi R N, Asha H S. Gestational diabetes mellitus: Practice guidelines. Curr Med Issues 2017;15:216-21

How to cite this URL:
Mathews JE, Preethi R N, Asha H S. Gestational diabetes mellitus: Practice guidelines. Curr Med Issues [serial online] 2017 [cited 2023 May 29];15:216-21. Available from: https://www.cmijournal.org/text.asp?2017/15/3/216/212379

Introduction

Even though the definition of gestational diabetes mellitus (GDM) has remained the same over several years, opinion regarding the detection and clinical management of GDM varies widely.

There are two aspects in the management of this condition. At one end is the fact that failure to recognize GDM leads to unnecessary morbidity. At the other end, overly aggressive treatment of GDM results in unnecessary intervention including small for gestational age babies.

Definition and Classification

GDM ^[1] is defined as carbohydrate intolerance of varying severity, detected for the first time in pregnancy.

Diabetes in pregnancy can be classified practically as gestational diabetes and pregestational diabetes which includes Type 1 and Type 2 diabetes. There is usually an overlap between GDM and type 2 diabetes which is identified for the first time in pregnancy during routine analysis. In India, the prevalence of gestational diabetes is between 14% and 22%.^[2],[3],[4]

Risk Factors

The common risk factors ^[1] for developing gestational diabetes mellitus are:

Prior GDM (in preceding pregnancy)
Obesity
Acanthosis nigricans
Family history of diabetes.

Maternal and fetal complications of gestational diabetes mellitus

The detection and treatment of GDM is important as it has consequences for both the mother and child.

Key points

Gestational diabetes mellitus[1] is defined as carbohydrate intolerance of varying severity, detected for the first time in pregnancy
Since the Indian population is at moderate to high risk, we recommend that all Indian women should be screened. Currently, the best screening modality in our population is the 75 mg oral glucose tolerance test using the IADPSG criteria
Eighty percentage of women with gestational diabetes can be treated with medical nutritional therapy and only 20% need additional therapy
Peri-conceptional glycemic control is the hallmark of the management of pregestational diabetes
Oral hypoglycemic agents have been shown to be comparable with insulin in treating women with moderate gestational diabetes and can be safely used. Both metformin and glibenclamide may be used, but metformin is recommended.
Glycemic goals in day-to-day practice are as follows:
Fasting blood glucose level. <100 mg/dl
1-h postprandial glucose level. <140 mg/dl
2-h postprandial glucose level. <120 mg/dl.
During the intrapartum period, maintain plasma glucose levels between 70 and 140 mg/dl.
Hypoglycemia. (blood glucose. <45 mg/dl) is a common problem in the neonates and is seen in 50% of macrosomic infants and in 5.15% of neonates with optimally controlled GDM in the mother.

Maternal complications

Women with preexisting diabetes have a risk of worsening of preexisting long-term complications such as retinopathy, proteinuria, and decline in glomerular filtration rate. There is also a higher risk of hypertension and cardiovascular disease and infection in this population
Important materno-fetal risks include macrosomia and cesarean delivery, spontaneous abortion, polyhydramnios, preeclampsia, preterm delivery, respiratory distress syndrome, and perinatal mortality
The mother has a strong risk of developing diabetes later (50% of mothers with GDM, in a study done by O'Sullivan et al., with a 28-year follow-up).

Neonatal complications

Macrosomia with or without birth injury (shoulder dystocia, brachial plexus injury)
Neonatal metabolic abnormalities: Hypoglycemia, hypocalcemia, and hypomagnesemia. Both hypoglycemia and hypocalcemia can increase the risk of seizures in neonates
Hyperbilirubinemia and respiratory problems
Risk of obesity and diabetes (in the child) later in life.

Congenital anomalies

Congenital anomalies are more common in mothers with GDM in the first trimester of pregnancy and when diabetes is poorly controlled (A1C <10.4% - risk of 4%–5%, A1C >10.4% - risk of 11%)

Two-third of anomalies involve the cardiovascular or central nervous system. Cardiac anomalies are most common (including great vessel anomalies)
Other anomalies include the following:
- Central nervous system (spina bifida/anencephaly): 7.2%
- Skeletal: cleft lip/palate
- Caudal regression syndrome is specific to diabetes

Screening and Diagnosis

Who should be screened?

Screening for GDM can be either selective based on the risk factors (obesity, previous diabetes, etc.) or it can be universal screening.

Since the Indian population is at moderate to high risk,^[2],[3],[4] we recommend that all Indian women should be screened. Currently, the best screening modality in our population is the 75 mg oral glucose tolerance test (OGTT) using the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria [Table 1].^[5]

Table 1: The International Association of Diabetes and Pregnancy Study Group consensus panel criteria to diagnose gestational diabetes mellitus

Click here to view

In June 2008, the IADPSG organized an international Workshop-Conference on Gestational Diabetes Diagnosis and Classification in Pasadena, California. The objective was to provide an internationally endorsed criterion for diagnosis and classification of diabetes in pregnancy.^[5] Around 225 conferees from forty countries reviewed the results of hyperglycemia and adverse pregnancy outcomes (HAPO) study,^[6] unpublished data of the HAPO study, and other studies that analyzed the effect of maternal glycaemia and perinatal and long-term outcomes in offspring.

The consensus panel identified the threshold value for diagnosis of GDM and overt diabetes in pregnancy.

This is a test done at 24–28 weeks' gestation – on those who have not been diagnosed to be diabetic as the contrainsulin hormones of pregnancy are maximum at this gestation.

Diagnosis

Diagnose as overt diabetes if fasting plasma glucose (FPG) level ≥126 mg/dl
Diagnose as GDM if one or more values equal or exceed thresholds
Diagnose as normal if all values on OGTT are less than thresholds.

Management of Gestational Diabetes Mellitus

Treatment of overt diabetes with FPG values >126 mg/dl and postprandial glucose value of >200 mg/dl is obvious. But should pregnant women with milder elevations of blood glucose levels be treated?

Two large randomized trials were conducted in an attempt to answer this question. A study involving 1000 women over a period of 10 years was conducted in Australia by Crowther et al.^[7] to assess the effect of intervention in pregnant women with mild diabetes (24–34 weeks of gestation with FPG levels <130 mg/dl and 2-h postprandial glucose measurement <200 mg/dl. The serious complications including perinatal death, shoulder dystocia, bone fracture, and nerve palsy were significantly lower in the intervention group than the control group. The number needed to treat to avoid one adverse outcome was 43. There was, however, no decrease in cesarean rates with the treatment of maternal hyperglycemia. Another multicenter, randomized trial for the treatment of mild gestational diabetes was done by Landon et al. in 2009 on pregnant women at 24–30 weeks' gestation with glucose challenge test values between 130 and 200 mg/dl.^[8] The women were then assigned to the control group who received routine obstetric care and treatment group who received nutritional counseling, diet therapy, and insulin if required. The major outcomes including macrosomia, large for gestational age, fat mass, cesarean delivery, shoulder dystocia, preeclampsia, and weight gain in pregnancy were significantly lower in the treatment group. In contrast to the previous study, they found that the cesarean rate was lower in those who had intervention.

The consensus was that moderate improvement was attained in neonatal outcome even when women were treated for milder degrees of hyperglycemia. Does this mean that there is no doubt regarding whether we need to screen and treat milder degrees of gestational diabetes? Is it cost-effective? The answer is not a straightforward yes.

Currently, according to the U. S. Preventive Services Task Force, the U. K. National Health Service, and Canadian Task Forces, there is no sufficient high-level evidence to make a recommendation for, or against, screening for GDM. Meanwhile, a recent study undertaken by the U. K. National Institute for Clinical Excellence concluded that “screening, diagnosis, treatment of GDM is cost-effective.”

Glycemic Control in Pregnancy

The objective of care in “diabetes in pregnancy” is to achieve pregnancy outcomes similar to those without diabetes. The management is straightforward – good glycemic control.

Type I diabetes is always controlled with medical nutritional therapy (MNT) and insulin. Most women with Type II diabetes would need similar treatment but with metformin now being safely used in the first trimester; this seems to be the acceptable mode of treatment in milder forms of Type II pregestational diabetes.

Peri-conceptional glycemic control is the hallmark of the management of pregestational diabetes [Table 2].

Table 2: Glycemic goals as suggested by the American Diabetes Association

Click here to view

Glycosylated hemoglobin level ≥10.4% is associated with 11% risk of congenital anomalies, as compared to 4%–5% risk below hemoglobin A1c (HbA1c) of 10.4%.

It should be emphasized that 80% of the women with gestational diabetes can be treated with MNT and only 20% need additional therapy. Of the women requiring additional therapy, only 25% need insulin therapy. The majority, i.e. 75% have moderate hyperglycemia (i.e., FPG levels ≥99 mg/dl and ≤130 mg/dl and/or 2-h postprandial levels ≥120 mg/dl and ≤250 mg/dl) and they can be treated only with oral hypoglycemics and may not need additional insulin.

Medical nutrition therapy

The goals of MNT are as follows:

Achieve normoglycemia
Prevent ketosis
Provide adequate weight gain
Contribute to fetal well-being.

Calorie allotment

The caloric requirement [Table 3] depends on the body mass index. A minimum of 1600–1800 kcal is required to prevent ketosis during pregnancy. Carbohydrates should contribute only 33%–40% of calories, proteins - 20%, and fats - 40%.

Table 3: Calorie requirement according to body mass index

Click here to view

Calorie distribution

Breakfast should contain the least proportion of calories - 10% of total calories, and should predominantly contain protein. Carbohydrate intake at breakfast should be limited because insulin resistance is greatest in the morning.

Lunch — 30% of total calories
Dinner — 30% of total calories
Snacks — 30% (distributed in three snacks)

Bedtime snack should be emphasized to prevent early morning hypoglycemia.

Recommended breakfast in South India

The recommended breakfast in South India is “Sundal” (boiled lentils) with milk or Ragi “kanji” (porridge/gruel) with roasted chana/moong dal.

Recommendations for diet control and medication

If the FPG at diagnosis is ≥120 mg/dl, consider immediate pharmacological therapy
If FPG at diagnosis is <120 mg/dl, MNT is recommended for 1–2 weeks, with glucose monitoring (fasting and 1 h postmeal)
If majority of FPG is >95 or 1-h postprandial plasma glucose is >140 mg/dl, then start on oral antihyperglycemic drug/insulin.

Oral hypoglycemic agents in pregnancy

The main concerns with the use of oral hypoglycemic agents (OHAs) in pregnancy are that there is limited experience, limited literature, doubts about teratogenicity, concerns about prolonged neonatal hypoglycemia, and controversy about placental transfer. However, over the years, evidence for the use of OHAs has shown that they are comparable with insulin in treating women with moderate gestational diabetes and can be safely used. When using OHAs, the following can be observed:

Risk of hypoglycemia is less
Less chance of insulin resistance
It is less expensive and
Compliance is better.

Glibenclamide and metformin are the two most studied drugs in pregnancy.

Glibenclamide

Glibenclamide acts by releasing insulin from β-cells. There is a reduction of serum glucagon levels and it potentiates the action of insulin on the target organ. Recent studies have shown that cord plasma levels of glibenclamide are almost 70% of maternal concentration.

Dosing

Glibenclamide can be started with 2.5 mg once a day and can be increased to a maximum of 7.5 mg twice daily. This is given before food.

Metformin

Metformin is a much better drug than glibenclamide. It is well known to improve insulin sensitivity, cause suppression of hepatic glucose output, cause increased insulin-mediated glucose disposal, and increase intestinal glucose use. It crosses the placenta but has no effect on placental transport or placental glucose uptake. In pregnancy, it is a class B drug with no adverse fetal effects. It is the only drug shown to be safe in the first trimester.

Dosing

Metformin can be increased gradually from a dose of 500 mg/day to a maximum of 3 g/day. It is given after food. Dose is increased every week. Duration of action is 10–12 h, so dosage has to be twice a day. It is contraindicated in liver impairment and renal insufficiency. Lactic acidosis and gastritis are the main side effects but these are not common.

Comparison between glibenclamide and metformin

Both glibenclamide and insulin can cause weight gain and hypoglycemia, but this is rare with metformin therapy. Metformin has the added advantage of being able to decrease appetite.

Glibenclamide increases fasting insulin levels while metformin decreases the fasting insulin levels. Metformin increases insulin sensitivity.

Evidence for the use of oral hypoglycemic agents in pregnancy

Initial evidence of the safety of use of OHAs in pregnancy was from South Africa where OHAs were being used for over 30 years. A cohort study published by Coetzee and Jackson ^[9] showed that there was no difference in perinatal mortality rate. Interestingly, the authors had started using OHAs because women refused to take insulin. In 2000, a landmark randomized controlled study published by Langer et al.^[10] confirmed that pregnancy outcomes with the use of glyburide (glibenclamide) were similar to insulin. This study was done on 404 women – 201 got glyburide and 203 got insulin. The diagnosis of gestational diabetes was based on a 100 g OGTT. They found that hypoglycemia, hypocalcemia, hyperbilirubinemia, and polycythemia were similar between the two groups. Perinatal mortality, still births, and neonatal death rates were similar. About 4% of women on glyburide had to switch to insulin. Four women in glyburide and 41 in insulin group had hypoglycemic episodes with blood glucose levels <39.6 mg/dl (P = 0.03). There were no episodes of severe hypoglycemia in either group. Incidence of preeclampsia and cesarean section was similar in both groups.

In 2008, the Metformin in Gestational diabetes study ^[11] published in the New England Journal of Medicine reported that 751 women were randomized into two groups –373 were given metformin and 378 were given insulin. Composite neonatal complications were similar in both groups. Neonatal hypoglycemia rates in neonates of women treated with metformin were (highly) significantly lesser than in those given insulin.

Insulin

Insulin is safe throughout pregnancy. The dose is 0.7–2 units/kg (present weight during pregnancy). Requirements are lower in the first trimester and become higher as the pregnancy advances.^[1]

Insulin regimens in pregnancy

The best regimen is the basal-bolus regimen as it is more physiological.

Basal-bolus regimen

The regimen is 3–4 injections/day (0.7–2 units/kg body weight).

And, thrice-daily regular insulin (or short-acting analogs) prior to meals plus neutral protamine Hagedorn once/twice daily (as a basal insulin).

It is easy to achieve targets with this regimen as it is more physiological.

Premixed insulin is used occasionally for the following reasons:

Convenient twice daily injections
Easy to learn dose adjustment.

Insulin pump may be required in persons in whom blood glucose levels are difficult to control.

Glycemic Goals

In day-to-day practice in our institution, the glycemic goals followed are:

Fasting blood glucose level <100 mg/dl
1-h postprandial <140 mg/dl
2-h postprandial <120 mg/dl.

During the intrapartum period, the plasma glucose levels are maintained between 70 and 140 mg/dl.

Patient education is very important and is the key to achieve these targets. Group education often helps because the feeling of loneliness is overcome.

Obstetric Management

Fetal monitoring

A baseline ultrasound must be done to assess fetal size
At 18–22 weeks, ultrasound screening for major malformations and fetal echocardiogram is recommended.
Recommendations for timing of delivery (weeks of gestation):
- AWomen on MNT (diet control) alone – 40–41 weeks
- Women on OHAs alone (easily controlled blood sugars) – 39–40 weeks
- Women on OHAs alone (difficult to control blood sugars) – 37–39 weeks
- Women on high doses of insulin – 37–38 weeks
- Vaginal delivery is preferred. Cesarean section is only for obstetric indication or fetal weight >4000 g.

Management of labor and delivery

Maternal hyperglycemia in labor worsens neonatal hypoglycemia. It should be noted that insulin requirements come down during labor
During the intrapartum period, the plasma glucose levels are maintained between 70 and 140 mg/dl. If the level goes beyond 140 mg/dl, insulin infusion needs to be given according to a sliding scale protocol
Glucose should be monitored at 1–4 hourly intervals during labor
In later stages of labor, dextrose should be started (nutritional requirement) and hourly blood glucose monitoring should be continued.

Immediate management of neonate

Hypoglycemia is a common problem. It is seen in 50% of macrosomic infants and in 5%–15% of neonates with optimally controlled GDM in the mother. Hypoglycemia in a neonate is defined as a blood glucose <45 mg/dl.

Management

A bolus of 2–4 ml/kg intravenous (IV) 10% dextrose should be given, should be checked after 15 min, and feeds should be started. If blood glucose is persistently low, IV dextrose infusion must be started.

Encourage early breastfeeding
Examine the infant for congenital anomalies.

Postpartum follow-up

In women with pregestational diabetes, the tight control is relaxed. For those on insulin, one-third to half of end pregnancy insulin dosage is usually recommended. We have to be very careful to avoid hypoglycemia because that may be fatal. Hypoglycemia kills, but hyperglycemia does not kill. Lactating mothers need less insulin.

In gestational diabetes, treatment in the postpartum period will need to be individualized. Those on diet control or on OHAs during pregnancy usually do not need any treatment in the postpartum period.

Women with gestational diabetes should be asked to have their blood glucose levels checked 6 weeks after delivery as they may be reclassified as type 2 diabetes and will need continued treatment.

Points to note

Check blood glucose before discharge for women who were on oral antidiabetic drugs or insulin.
Breastfeeding helps in weight loss
Insulin is compatible with breastfeeding
Glibenclamide is not secreted in breast milk.
Metformin is secreted in breast milk but is not associated with adverse effects
Lifestyle modification should continue irrespective of glucose levels to prevent permanent diabetes.

Future risks to mother

A 75 g OGTT should be done for all women with GDM, 6–12 weeks after delivery. About 75%–80% are normoglycemic and 20% have impaired glucose tolerance.

The risk of developing type 2 diabetes is 3.7% at 6 months, 4.9% at 15 months, and 35%–60% develop diabetes over the next 10 years. The risk of recurrence of GDM is 30%–69%.^[12]

Risk of developing diabetes mellitus in offspring

If the father has type 1 diabetes, the risk is 6%–8%, it is 2%–5% if the mother has type 1 diabetes, and is 10%–25% if both are affected.^[13],[14]

In type 2 diabetes mellitus, if a single parent is diabetic, the risk is as follows:^[13],[14]

Fourteen percentage if the parent was diagnosed at <50 years of age
Eight percentage if the parent was diagnosed at >50 years of age
The risk is 50%–60% if both are affected.

Preconception counseling

Contraception should be advised for spacing until glycemic control is achieved. Injection Depot Provera 150 mg every 3 months is a good temporary method of contraception for individuals with diabetes.

Preexisting diabetes

Glycemic control should be achieved to target HbA1c <6.5%.

Folic acid supplementation: 5 mg/day (should begin 3 months before planning pregnancy).

Try and achieve normal body weight with diet modification and exercise
Stop unsafe OHAs, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, β-blockers, statins, fibrates, and niacin.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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