Gestational diabetes mellitus

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Following a diagnosis of GDM, offer the woman a review in a joint diabetes and antenatal clinic within a week and ensure that her primary care team is informed.[4]

This clinic should be in contact with the woman every 1 to 2 weeks throughout pregnancy for assessment of glycaemic control.

For patients diagnosed with GDM, the main goal of treatment is good glycaemic control throughout pregnancy in order to reduce the risk of fetal macrosomia, trauma during birth (for mother and baby), induction of labour and/or caesarean section, neonatal hypoglycaemia, and perinatal death.[4][23]

In addition, treatment for GDM reduces the risk of pre-eclampsia and hypertensive disorders in pregnancy.[56][57] One Cochrane systematic review on the effect of various management strategies on maternal and infant outcomes found that specific treatment for mild GDM, including dietary advice and insulin, reduced the risk of maternal and perinatal morbidity, although it was associated with a higher risk of labour induction.[58] [ ]

Test urgently for ketonaemia if a woman with GDM presents with hyperglycaemia or acute illness.[4]

Education

The first step in managing gestational diabetes is to discuss the implications of the diagnosis (both short and long term) for the woman and her baby:[4]

Explain that good blood glucose control throughout pregnancy reduces the risk of fetal macrosomia, trauma during birth (for mother and baby), induction of labour and/or caesarean section, neonatal hypoglycaemia, and perinatal death.[Evidence C]
Explain that lifestyle interventions, including diabetes self-management education, healthy eating, physical activity, and self-monitoring of blood sugar levels, are essential for women with GDM.[3][59]
Depending on the regulations where you practise, this may include giving localised advice on driving with diabetes for those requiring pharmacological treatment (e.g., Driver and Vehicle Licensing Agency [DVLA] rules in the UK).
DVLA: diabetes and driving Opens in new window

Glucose monitoring

Self-monitoring of blood glucose is initiated to assess fasting and post-prandial glycaemia and guide therapy.[4] The UK National Institute for Health and Care Excellence (NICE) recommends the following:[4]

Advise all women with GDM to test their fasting and 1-hour post-meal capillary glucose levels daily
If a woman with GDM is on multiple daily insulin injections, advise her to also test glucose levels before meals and at bedtime.

Advise women with GDM to maintain their capillary plasma glucose below the following target levels:[4]

Fasting: 5.3 mmol/L (95 mg/dL)
1 hour after meals: 7.8 mmol/L (140 mg/dL)
2 hours after meals: 6.4 mmol/L (115 mg/dL).

These target levels are the same as for any pregnant woman with any form of diabetes.

If the above targets cannot be achieved without problematic hypoglycaemia, agree individualised targets that take account of that risk.[4]

Women taking insulin should also aim to keep their capillary glucose levels above 4 mmol/L (72 mg/dL).[4]

In women treated for GDM, higher median fasting glucose during the first 2 weeks of diet therapy was associated with increased neonatal fat mass and elevated C-peptide; during the last 2 weeks before delivery it was associated with macrosomia, large-for-gestational-age fetus, and elevated C-peptide.[60]

Diet and exercise

Dietary advice is central to the control of GDM, and many women are adequately treated with diet and lifestyle modification alone. However, data are limited concerning different types of dietary advice.[61]

NICE recommends a 1 to 2 week trial of diet and exercise changes alone for women with GDM who have a fasting plasma glucose (FPG) <7 mmol/L (<126 mg/dL) at diagnosis (and who have no complications such as a large-for-gestational-age fetus or hydramnios).[4][Evidence C]

Refer any woman with GDM to a registered dietitian, if available.[3][4][21]

Expert opinion suggests that women should be advised to choose carbohydrates from low glycaemic index (GI) sources and lean proteins.[4]
Caloric needs are determined by pre-pregnancy ideal body weight according to expert opinion: 30 kcal/kg for those with normal weight and 35 kcal/kg for underweight patients.[62]
Evidence suggests that a low GI diet may be the best option for women with GDM. While some studies have suggested reducing carbohydrates to 40% to 45% of total daily calories reduces post-prandial hyperglycaemia, one meta-analysis of dietary interventions concluded that a low GI diet was associated with a less frequent need for insulin and lower infant birth weights than calorie-restricted diets, low carbohydrate diets, or other diets.[63][64]
The American Diabetes Association recommends a diet with a balance of macronutrients (i.e., carbohydrates, protein, fats), including nutrient-dense whole foods such as fruits, vegetables, legumes, whole grains, and foods containing healthy fats with n-3 fatty acids (e.g., nuts, seeds, fish).[3] A diet that severely restricts any macronutrient class should be avoided.[3]

Moderate-intensity exercise during pregnancy (e.g., brisk walking, easy jogging, or swimming) is recommended and has been associated with lowering of maternal glucose levels in some, but not all, studies.[65]

NICE recommends that women with GDM should be advised to exercise regularly (e.g., walking for 30 minutes after a meal).[4]

Metformin

Guidelines differ on the use of oral anti-hyperglycaemic agents in women with GDM whose glucose levels are not controlled by diet and exercise. Their role remains a matter of debate, largely owing to historically sparse data on long-term offspring outcomes, although in practice they are widely used.[66] Check your local protocol.

One large, register-based cohort study from Finland found no increased long-term risk to offspring associated with pregnancy exposure to metformin compared with insulin.[67] Following a European review of data from this study, the metformin prescribing information now states that it can be considered for use during pregnancy and the periconceptional phase as an addition or an alternative to insulin, if clinically needed. Thus, while metformin is not specifically licensed in the UK for the treatment of gestational diabetes, it can be used in pregnancy for both pre-existing and gestational diabetes.

NICE concluded that metformin is a safe option that can enable some women with GDM to achieve euglycaemia without the need for insulin treatment.[Evidence B] NICE recommends to:[4]

Offer metformin if a woman’s capillary plasma glucose levels are persistently above target levels after 1 to 2 weeks of dietary and exercise changes. If metformin is contraindicated or not tolerated, offer insulin instead.
Consider metformin as an adjunct for any woman with GDM who is treated with insulin.

Metformin reduces hyperglycaemia by decreasing hepatic gluconeogenesis and glycogenolysis. Limited evidence is available to suggest that it decreases the composite outcome of infant mortality or serious morbidity. [ ] One systematic review comparing outcomes of GDM treated with oral antihyperglycaemic agents versus insulin found that metformin and insulin therapy yielded similar outcomes.[68] One meta-analysis of 35 randomised controlled trials (RCTs) reporting on pregnancy outcomes in women who used metformin for any indication found that gestational weight gain was lower in women randomised to metformin versus other treatments (1.57 kg ± 0.60 kg). The risk of pre-eclampsia was also reduced (OR 0.69, 95% CI 0.50 to 0.95) but the risk of gastrointestinal side-effects was greater in women taking metformin compared with other treatment groups.[69]

Metformin freely crosses the placenta to achieve measurable concentrations in cord blood at concentrations similar to or higher than the maternal concentration.[70][71][72] Despite this, follow-up data have suggested no adverse developmental effects and no early differences in overall body composition in offspring.[67][73][74] Some commentators have recommended that due to the potential for growth restriction or acidosis in the setting of placental insufficiency, metformin should not be used if the fetus is at risk of experiencing an ischaemic environment, including placental insufficiency, hypertension, pre-eclampsia, or growth restriction.[66]

The efficacy of metformin alone is unclear; in one large RCT, 50% of women in the metformin group required supplemental insulin for maintenance of glycaemic control, particularly those with fasting hyperglycaemia, and nearly all women required the maximum metformin dose.[75] Another study concluded that metformin can provide adequate glycaemic control in around two-thirds of women with GDM who require pharmacological therapy.[76] One RCT examining the use of insulin with metformin or placebo in women with type 2 diabetes in pregnancy found no difference between women who received metformin and those receiving placebo in a composite of neonatal morbidity and mortality. However, women treated with metformin had better glycaemic control, lower insulin requirements, less gestational weight gain, and fewer caesarean births than women in the placebo group. Infants of mothers taking metformin weighed less, were less likely to be extremely large for gestational age (birthweight >97th centile), and were less likely to weigh 4 kg or more at birth, compared with infants born to mothers taking placebo. Additionally, metformin-exposed infants displayed reduced adiposity with reduced skinfold thicknesses, abdominal circumference, and fat mass. However, a higher proportion of babies were small for gestational age (birthweight <10th centile) in the metformin group than in the placebo group.[77]

One systematic review and meta-analysis comparing glibenclamide or metformin versus insulin or versus each other in women with gestational diabetes requiring drug treatment found that metformin was superior to glibenclamide. Glibenclamide was shown to be inferior to both insulin and metformin, while metformin (plus insulin when required) performed slightly better than insulin alone. The authors concluded that glibenclamide should not be used for the treatment of women with gestational diabetes.[78] However, there are limited data comparing metformin with glibenclamide. [ ]

Insulin therapy

NICE recommends immediate initiation of insulin, with or without metformin, for women with GDM who:[4]

Have FPG level ≥7.0 mmol/L (≥126 mg/dL) at diagnosis
Have FPG level of 6.0 to 6.9 mmol/L (108-124 mg/dL) at diagnosis in the presence of a large-for-gestational-age fetus or polyhydramnios.

This is in order to get glucose levels controlled as quickly as possible. Patients started on insulin are likely to have insulin prescribed throughout pregnancy.

In addition, insulin should be offered as an additional therapy for women with FPG <7.0 mmol/L (<126 mg/dL) at diagnosis who cannot achieve satisfactory glycaemic control with metformin combined with diet changes and exercise.[4]

Insulin therapy is also an alternative to metformin for women whose capillary glucose levels are not controlled by diet and exercise alone and in whom metformin is contraindicated, unacceptable, or not tolerated.

Insulin needs are highly variable. Requirements increase throughout pregnancy and average 0.8 units/kg/day in the first trimester, 1 unit/kg/day in the second trimester, and 1.2 units/kg/day in the third trimester.[62]

Insulin therapy requires highly individualised titration.
For isolated fasting hyperglycaemia, use intermediate-acting insulin (e.g., insulin isophane NPH [Neutral Protamine Hagedorn]) or long-acting insulin (e.g., insulin detemir, insulin glargine) at bedtime and then adjust the dose to achieve fasting blood glucose <5.3 mmol/L (<95 mg/dL).[79]
To address post-prandial hyperglycaemia, one approach is to use intermediate-acting or long-acting insulin once or twice daily, with short- or rapid-acting prandial insulin (e.g., insulin lispro, insulin aspart) titrated to meet glycaemic targets.[79]
Insulin is titrated according to maternal dietary intake to meet target blood glucose levels.[3][49]

In the UK, NICE recommends insulin isophane NPH as the first choice for background insulin during pregnancy, given once (to provide night-time coverage) or twice daily, although insulin detemir and insulin glargine are also commonly used. NICE also states that the rapid-acting insulin analogues, insulin lispro and insulin aspart, have advantages over soluble human insulin during pregnancy.[4]

Human and analogue insulins are the most extensively studied in pregnancy and are generally considered safe. Evidence suggests that the rapid-acting insulin analogues, insulin lispro and insulin aspart, are also safe in pregnancy.[4][21][80][81] These rapid-acting insulins offer increased convenience and improved post-prandial control; however, there is little information to support superiority of any insulin analogue type either during or outside of pregnancy.[79][82] None of the current human insulins cross the human placenta at normal therapeutic doses.[3][79] Although there is more limited experience with long-acting insulin detemir and insulin glargine, there is no evidence of adverse maternal or fetal outcomes.[81][83][84] Experience in pregnancy with the rapid-acting insulin glulisine is limited, and this insulin analogue should be used only when benefit is thought to outweigh risk relative to other insulins.[85]

Advise any woman who is taking insulin about the risks of hypoglycaemia and impaired awareness of hypoglycaemia during pregnancy.[4]

Pregnant women taking insulin should always have a fast-acting form of glucose available (e.g., dextrose tablets or glucose-containing drinks).

Antenatal fetal monitoring

Protocols for antenatal fetal monitoring for women with GDM vary, so check your local protocol.

In the UK, NICE recommends the following:[4]

Offer ultrasound assessment of fetal growth and amniotic fluid volume every 4 weeks from 28 to 36 weeks of gestation.
- If problems are identified, more frequent ultrasound assessments may be required. In line with the NHS England Saving Babies’ Lives Version Three Care Bundle, all women should be made aware of the importance of monitoring fetal movements and seeking medical review if their baby’s movements are reduced.[86]

Ultrasonographic estimates of fetal weight may be useful in planning timing and route of delivery, with recognised limitations.

NICE recommends against the routine use of fetal artery doppler recording, fetal heart rate recording, and biophysical profile testing before 38 weeks of gestation, unless there is a risk of fetal growth restriction.[4]

Timing and mode of delivery

Advise women with GDM to give birth no later than 40 weeks and 6 days of gestation.[4]

For women with maternal or fetal complications, earlier delivery may be indicated.
Some maternity units will also offer delivery before 40 weeks and 6 days for women with GDM who are taking insulin or metformin.

Offer elective birth by induced labour or (if indicated) by caesarean section to women who have not given birth by 40 weeks and 6 days.[4]

Diabetes should not be considered a contraindication to vaginal birth after a previous caesarean section.

If ultrasound assessment shows the fetus is large for gestational age, explain the relative risks and benefits of vaginal birth, induction of labour, and caesarean section to the woman.[4]

As increasing fetal size is associated with increased risk of shoulder dystocia and birth trauma, assessment of fetal size, either clinically or with ultrasound, may be useful in planning delivery route. Ultrasound overestimates the prevalence of large-for-gestational-age fetal weight in women with GDM.[87]
Although it is reasonable to offer caesarean delivery to reduce the risk for shoulder dystocia if the estimated fetal weight is >4.5 kg, the estimation of fetal weight is imprecise regardless of modality, and therefore counselling should be individualised.[88]

Labour

Advise women with GDM to deliver in a hospital with 24-hour advanced neonatal resuscitation capacity.[4]

Capillary plasma glucose should be monitored every hour during labour and birth or from the morning of elective caesarean section.[4][89] If general anaesthesia is used, monitoring should be every 30 minutes until the woman is fully conscious.[89]

There are no large RCTs addressing whether intrapartum compared with antenatal glycaemic control lessens the risk of neonatal hypoglycaemia; however, based on limited evidence, avoiding maternal hyperglycaemia during labour in women with GDM is recommended. Intravenous insulin may sometimes be needed to achieve this.[90]

NICE recommends that women whose capillary glucose levels cannot be maintained between 4 and 7 mmol/L (72-126 mg/dL) should be started on intravenous dextrose and insulin infusions.[4]
The Joint British Diabetes Societies for Inpatient Care Group recommends that glucose levels (capillary, flash, or continuous glucose monitoring ) are maintained during labour in either the target range advocated in the NICE guidelines (4 to 7 mmol/L [72-126 mg/dL]) or in the more liberal range of 5 to 8 mmol/L (90-144 mg/dL) due to lack of randomised controlled trial evidence for either target.[89] Some women with GDM may require variable rate intravenous insulin infusion to achieve target glucose levels.[89]

Immediately after placental delivery, a large reduction in insulin requirement occurs, and this must be anticipated to avoid hypoglycaemia.

Most women with GDM can stop insulin after delivery.

After delivery

Stop all glucose-lowering therapies after delivery.[4]

Repeat blood glucose monitoring before discharge from hospital, either as a one-off or as a period of continued postnatal monitoring, to exclude persistent hyperglycaemia.
Women should be reminded of the symptoms of hyperglycaemia, the risk of recurrence in future pregnancies, and the risk of developing type 2 diabetes in the future.

Some women with GDM will have persistent hyperglycaemia in the days after delivery that will justify medical management for diabetes and perhaps for hypertension, microalbuminuria, and dyslipidaemia.[91] See Monitoring.

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