Gestational Diabetes

Introduction

Resistance to insulin is a normal physiological response in pregnancy, thought to be induced by maternal hormones.  However, in some women, this is severe enough to result in gestational diabetes mellitus (GDM). In these women, there is reduced ability of the pancreas to produce enough insulin to overcome the insulin resistance.
Gestation diabetes is defined as – Any hyperglycaemia with first onset or presentation during pregnancy.
The incidence of gestational diabetes is increasing, in line with type 2 diabetes. It affects 2-10% of pregnancies (varies due to the criteria used) in developed countries such as the UK and Australia.
In most cases, it is asymptomatic and diagnosed on routine testing between 24-28 weeks.
The complications of gestational diabetes are similar to those of overt diabetes and include macrosomia (large baby for gestational age – which can cause problems in labour), neonatal hypoglycaemia and hyperbilirubinaemia. Treating GDM reduces these risks back to the baseline level of normal pregnancy.
Women with pre-existing type 1 or type 2 diabetes should be considered separately (see “Diabetes in Pregnancy” below) – and are usually referred to a endocrinologist or specialist diabetes in pregnancy service at the start of their pregnancy.

Epidemiology and Aetiology

  • Affects 2-10% of pregnancies
  • Risk factors:
    • Previous GDM
    • >35 years
    • Obesity (BMI >25, especially BMI > 35)
      • Note that women with BMI >27 should be given advice on weight loss if planning pregnancy
    • PCOS
    • Smoking
    • Previous stillbirth
    • Previous ‘large’ baby (>4.5Kg)
    • FH of type 2 diabetes
    • More common in Asians, those from the middle east and Black Africans
    • 40% of women with GD have none of these risk factors!
  • Regular exercise during pregnancy is protective against development of gestational diabetes

Diagnosis

  • Guidelines are not always clear, or conflict, as to who to test and when
  • Most guidelines agree that an Oral Glucose Tolerance Test is the most useful diagnostic investigation, and that the best time to do this is between 24-28 weeks
  • NICE recommends testing any women with previous GDM at any stage of pregnancy (with OGTT), and repeating at 24-28 weeks if the first test is normal, AND women with any other risk factor be tested at 24-28 weeks
  • The Australasian Diabetes in Pregnancy Society recommends ALL pregnant women should be tested between 24-28 weeks, and women with any risk factors should have a random blood sugar level in their initial routine ante-natal blood tests
    • If BGL >7 – do OGTT
    • If BGL <7 or OGTT performed and is normal, repeat at 24 weeks
  • Interpreting the oral glucose tolerance test
    • 75g of glucose is given – usually in the form of a drink – to a fasted (>8 hours) patient. Usually the test is performed in the morning (e.g. 8 or 9am, with the patient fasted from midnight the night before)
    • Blood sugar readings are taken at 1 hour and 2 hours after the test
    • An abnormality in ANY of the below is enough to diagnosed gestational diabetes (note that different guidelines have “abnormal” values – which is very confusing for medical students and also doctors practising in this field. The values given below are the “new” revised values from the Australasian Diabetes in Pregnancy Guidelines – I chose these because they are the most recent guideline that I came across):
      • Fasting >5.1 mmol/L
      • 1 hour post glucose >10.0 mmol/L
      • 2 hours post glucose >8.5 mmol/L
  • These testing regimens try to avoid a common pitfall of diagnosis – which is that glucose levels naturally rise in the third trimester, and thus relying purely on a glucose level, especially if only mildly elevated in the third trimester, may not necessarily indicate GDM
  • With these “new” cut-off values for diagnosis, the rate of GDM is expected to be about 12-14%. This is likely to have significant impacts on service provision

The role of HbA1c testing in gestational diabetes is still debated. It is recommended to check HbA1c in all women who are diagnosed with GDM – however, if the result is abnormally high this is usually an indicator or pre-existing Type 2 Diabetes, rather than an indicator or useful assessment of gestational diabetes.

All patients with GDM should have foetal USS every 4 weeks from 38 to 36 weeks to assess foetal growth and amniotic fluid volume.

Pathology

During pregnancy, maternal insulin sensitivity is naturally reduced. This increases maternal blood glucose levels, in order to provide enough glucose for the foetus, particularly in the third trimester. This means that mildly glucose levels in the third trimester should be interpreted with caution.
  • The hormone Human placental lactogen (aka Human Chorionic Somatomammotropin) is responsible for reduce insulin sensitivity. It also alters maternal fat metabolism, releasing fatty acids as an alternate energy source for the mother, freeing up glucose for the foetus.
  • The normal physiological response to this increased insulin resistance is for the body to produce more insulin. However, in some women this does not occur, resulting in hyperglycaemia
  • It is often genetic – and tends to occur more in those who have a genetic predisposition for T2DM

Clinical features and presentation

Diagnosis is not always very easy. It is often asymptomatic, and only discovered on screening. The common diabetic symptoms (thirst, hunger, polyuria, tiredness) are not particularly common, but are also seen in normal pregnancy in the third trimester anyway.
Baby’s risk with diabetic mother
  • The risk of baby’s problems is greatest when glycaemic control is poor around the time of conception.
  • Fetal macrosomia – this means big baby! The excess maternal glucose the baby is exposed to results in the storage of more fat than normal. Definition – abdominal circumference >70th percentile.
  • The newborn may be hypoglycaemic, as they have been producing their own endogenous insulin during pregnancy to counteract they hyperglycaemia of the mother. This is usually self-limiting, but may require IV glucose.
  • Increased risk of shoulder dystocia during delivery
  • Increased risk of jaundice
  • Increased risk (2x) of congenital defects: congenital heart disease, respiratory distress syndrome, NTD’s. the risk of defects is inversely related to level of control of the gestational diabetes.
    • The risk of congenital defect is highest in type II diabetes, and lowest in type I. the risk in gestational diabetes is moderate.
  • Increased risk of type II diabetes in later life
  • Increased risk of obesity in childhood
  • Increased risk of stillbirth

 

Mother’s risks

  • Increased risks of vaginal tears
 

Complications

Increased risk of type II diabetes in the mother

  • 50% will develop type II diabetes within 15 years
  • 50% of those requiring insulin will develop type II within 5 years
  • Increased risk of cardiovascular disease – independent of T2DM

Increased risk of stillbirth – to reduce this risk, the many mother have a caesarean at 38-39 weeks (instead of the usual 40)

  • All mothers shuld be offered caesarean or induced birth after 38 full weeks. Those with proven Macrosomia should be informed of the risks of vaginal birth.

Increased risk of GD in subsequent births (30-85%) – particulary if pregnancy occurs within 1 year.
Type I diabetes – any women with type I diabetes who becomes unwell during pregnancy should have DKA excluded as a differential!

 

For the baby

  • Increased risk of obesity
  • Impaired intellectual achievement
  • Birth injuries – shoulder dystocia, fractures, nerve palsies – these are all problems associated with macrosomia (large baby)

Classification

Some classify gestational diabetes into two types:
  • Type A1 – abnormal OGTT, but normal glucose levels during fasting and two hours after meals
    • Can usually be controlled with diet and exercise
  • Type A2 – abnormal OGTT and high levels of glucose during fasting and 2 hours after meals
    • More likely to require pharmacological intervention

Treatment

Evidence for the effectiveness of treatment is mixed. It is thought that treatment reduces the risk of congenital defects and labour complications, but does not necessarily reduce the risk of caesarean section or perinatal mortality.
Glucose levels should be monitored every 1-2 weeks during pregnancy
Similar to the normal management of type II diabetes: try diet and exercise modifications first, e.g.:

Exercise – low impact activities are encouraged – such as walking, swimming, yoga and pilates. Particularly important in those with BMI >27Kg. These women may also be instructed to restrict calorie intake.

  • Aim for 30 minutes a day of “moderate intensity” exercise (“sufficient to induce slight breathlessness”). This is proven to reduce insulin resistance.
  • Weight loss is not advised, but limiting weight gain may be appropriate

Meals – eat regular meals, focus on the quantity and quality of carbohydrates and control fat intake. Aim for 175g of carbohydrates daily. Recommend use of complex carbohydrates, which reduce high peaks of glucose, and are digested slowly (“low GI foods”). Also, peak glucose levels are associated with breakfast more than with other meals, so it may be necessary to restrict carbohydrate intake at breakfast.

  • GI – foods are given a rating from 1- 100, e.g. glucose (100) and spaghetti (41). Foods below 55 are considered low GI.
  • Salt – monitor salt intake
  • Fruit + Veg – at least 5 portions a day!
  • Oily fish, lean meat, and polyunsaturated fats are also recommended
  • Consider referral to dietician
  • Be wary of severe calorie restriction, which can cause ketonuria and is related to adverse pregnancy outcomes – such as small for gestational age baby

Advise patients to check blood sugar level daily at home:

  • On waking, first thing int he morning, whilst still fasted – aim for <5.3 mmol/L
  • 2 hours after each meal (i.e. 3x per day) – aim for <6.4 – 6.8 mmol/L
For most (80-90%) patients, diet and exercise measures are enough. If diet and exercise are unable to bring glucose levels under control within 2 weeks, then medical interventions may be considered. Usually this is done with the support of an endocrinologist or a specialist diabetes in pregnancy service – and patients will require a referral from primary care to access these services.

Metformin +/- Insulin

Until 2008, it was recommended that type II diabetic mother considering pregnancy, and those with gestational diabetes should avoid oral medications, and go on to using insulin for the duration of the pregnancy. However a large study in Australia and NZ confirmed that oral treatments are as effective, and do not increase the risk of birth defects relative to insulin.

Metformin is thought to be particularly useful in obese women.

Indications for insulin

  • Glucose not controlled with diet + exercise + metformin
  • Patients with a fasting sugar >7.0 mmol/L at diagnosis
  • Patients with evidence of complications (e.g. macrosomia, hydramnios) and a fasting BSL >6.0 mom/L

Rapid acting insulins (aspart and lispro) are more effective than endogenous insulins for controlling diabetes during pregnancy.
Insulin pumps should be recommended to those whose diabetes is not adequately controlled by multiple daily manual injections.

  • If insulin is used during pregnancy, the dose is usually increased by 50%
  • Warn about the risk of hypoglycaemia, how to recognise it and how to treat it
  • Women on insulin should always carry within them a rapid acting glucose – e.g. glucose-containing drinks or dextrose tablets
  • Any women who is on insulin and unwell should have ketones checked

Other oral agents

  • Only metformin is usually recommended
  • In circumstances where sugars are not controlled with metformin and lifestyle measures, and the patient declines insulin, the glibenclamide may be considered
  • Other oral agents are not recommended
Glucose during labour
Should be monitored every hour, and kept between 4-7 mmol/L
  • Consider Insulin + dextrose infusion in those with type I, or poorly controlled diabetes.

The time of birth

  • Patients should deliver no later than 40+6 weeks
  • If they have not delivered by this stage, offer induction or caesarian section
  • Consider earlier elective than this if there is any evidence of complications (e.g. macrosomia, polyhydramnios). GDM in itself without complication is not an indication for pre-term induction
  • GDM alone is NOT a contraindication to vaginal birth in the context of previous caesarian section
After Birth
Feeding of the baby should be encouraged – to reduce risks of hypoglycaemia in the newborn.
  • Treatment can be ceased immediately after birth in GDM
  • In T1DM and T2DM, treatment should continue, but doses of medications may need to be altered
  • Breastfeeding – glibemclamide and metformin are safe to take whilst breastfeeding. Other oral agents should be avoided.
    • Breastfeeding itself is thought to have advatanges to both the mother and the baby in reducing their risk of being overweight.

Treatment can usually be stopped after birth, as the insulin resistance returns to normal. NICE recommends a random glucose test at the 6 week checkup, and if this normal, treatment can be stopped. If this is not normal, then patients should undergo further investigation for T2DM – e.g. OGTT or HbA1c).

  • In Australia, an OGTT is recommended at 6 weeks – but HbA1c is considered a suitable alternative. Fasting blood glucose is not recommended.

Follow-up

  • Recommend ongoing diet and lifestyle advice after birth (the same as given during GDM in pregnancy)
  • Patients have an increased risk of T2DM in the long term
    • Also have a 50% of GDM in any future pregnancy
  • In UK, recommended to perform annual HbA1c annually to all patents with previous GDM
  • In Australia – recommended to perform an OGTT at 6-12 weeks postpartum to screen for T2DM, and then a fasting blood sugar every 3 years

Diabetes in Pregnancy

Before pregnancy
Education of diabetic women of childbearing age from adolescence upwards is important. Tell them about the need to plan pregnancies so that they can unsure:

The diabetes is under control before pregnancy to give them the greatest chance of keeping it under control during pregnancy. Control should be measured with HbA1c test (should be below 6.1 for those planning on / who are pregnant. Those with HbA1c >10 should be strongly advised to avoid pregnancy!
The need to take folic acid supplements – 5mg/day when planning pregnancy and for 3 months after.
In type II diabetic mothers – Increased risk of birth defects

  • Advise to take 5mg folic acid supplements when planning to conceive and for the first 12 weeks of pregnancy
  • Risks include:
    • Birth defects mentioned above
    • Increased risk of miscarriage
    • Increased risk of stillbirth and neonatal death
  • Women with BMI >27 who are planning to become pregnant should be given advice on how to lose weight

Targets for control in pregnant diabetics:

  • Fasting glcusoe – 3.5 – 5.9
  • 1 hour post prandial <7.8

Investigations and screening

  • Fetal USS – four chamber view of heart and outflow tracts at 18-20 weeks
  • Routine monitoring of fetal wellbeing is not recommended, unless pregnancy continues past 39 weeks.

Control of diabetic complication risk factors

  • HypertensionACE-i and angiotensin-II antagonists should not be used in pregnancy! Use alternative treatments if planning a pregnancy or as soon as pregnancy is known. Use
    • Methydopa
    • Methynifedipine
  • Statins – should be discontinued if planning pregnancy or as soon as pregnancy is known
  • Retinopathy – up to 20% will experience some retinopathy during pregnancy
  • Nephropathy – may worsen during pregnancy, avoid pregnancy is severe (e.g. creatinine >100, urea >4.5).

Antenatal care in diabetes

There is an increased level of care and surveillance for diabetic mothers. Typical measures, in addition to the normal antenatal care, may include:

Blood glucose monitoring – targets should be set, and reviewed every 2 weeks with a medical professional
Retinal digital screening

  • As soon as pregnancy confirmed (if not screened for >12 months)
  • Perform at first ante-natal appointment
    • Perform at 16-20 weeks if previous result positive
    • Perform at 28 weeks if previous result negative
  • 20% of diabetic mothers will develop proliferative retinopathy during pregnancy

Renal screening

  • At first appointment – dipstick for protein, albumin, creatinine. Refer to nephrologist if creatinine >120, or protein >2g/day
  • Thromboprophylaxis should be given to all those with protein excretion >5g/day

References

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