Diabetes Mellitus

د. حسين محمد جمعه

اختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2011

Diabetic problems in pregnancy

©BMJ Learning 2011

Key points

The oral hypoglycaemic agents metformin and glibenclamide can be used to treat gestational diabetes if diet and exercise are not sufficient. At every contact with a woman of childbearing age who has diabetes, healthcare professionals should consider checking whether the patient is using effective contraception, and, if not, offering prepregnancy counselling.

Prepregnancy counselling and care should include advice and practical measures to help achieve tight glycaemic control before pregnancy. This has been shown to reduce the risk of congenital malformation and adverse events, such as miscarriage, stillbirth, and neonatal death.
It is also an opportunity to discontinue teratogenic medication and optimise other complications

All women with pregestational diabetes should receive high dose folic acid (5 mg once daily) preconceptually until the end of the first trimester .
Obstetricians should offer women elective delivery after 38 weeks’ gestation, by induction of labour or elective caesarean section, if the fetus is normally grown.
Care should be provided by a multidisciplinary team, including an obstetrician, diabetologist, dietitian, diabetes specialist nurse, and a midwife with an interest in diabetes .


Clinical tips
NICE has approved the use of metformin and glibenclamide for managing pregnancy complicated by type 2 diabetes, or gestational diabetes, or both.
Glibenclamide is recommended only for use after the first trimester of pregnancy. But use of these medicines in pregnant women is not a licensed indication in the UK, and you should discuss this (and document your discussion) with the patient.

For women with type 1 diabetes and those with type 2 diabetes requiring insulin therapy, a basal bolus insulin regimen (for example, isophane and analogue rapid) is preferred for managing and achieving tight glycaemic control.
NICE does not recommend the use of analogue basal insulins (glargine, detemir), but many maternity units do not convert patients’ medication back to isophane, and probably most believe the reduction in nocturnal hypoglycaemia on basal analogues is advantageous to tight control .

You should inform women using insulin therapy that they might experience

reduced hypoglycaemic warning signs and symptoms, particularly during the first trimester. You should discuss (and document) safe driving if the patient drives.
You should also discuss management of hypoglycaemia and consider prescribing oral glucose preparations and glucagon .
Target blood glucose levels should be individualised, discussed, and documented.

Table 1. WHO thresholds for the 75 g oral glucose tolerance test

Fasting blood sugar
Two hours blood sugar after glucose tolerance test
Normal
<6.1 mmol/l
<7.1 mmol/l
Gestational diabetes
≥6.1 mmol/l
>7.8 mmol/l
Diabetes mellitus
≥7.0 mmol/l
≥11.1 mmol/l
• Diagnostic criteria for diabetes in pregnancy
• Gestational diabetes is diabetes first detected during pregnancy. Clearly, some people may have previously undiagnosed diabetes, but this cannot be assumed or confirmed until postnatal testing is undertaken. Unless the patient presents with symptoms, it is usually diagnosed using a 75 g oral glucose tolerance test. The World Health Organization (WHO) thresholds for this test are given in Table 1.


Gestational diabetes
Physiology
In normal pregnancy glucose metabolism is altered leading to a state of relative insulin resistance. This is due to hormones, whose actions are antagonistic to insulin, produced predominantly by the placenta, which include human placental lactogen, glucagon, and cortisol. During a pregnancy in a person without diabetes it is usual for insulin production to double from the first to the third trimester. In women with gestational diabetes there is insufficient secretion of insulin to overcome this relative insulin resistance, and the increased insulin requirements.

Gestational diabetes is glucose intolerance or diabetes first detected in pregnancy. It affects around 20 000 women a year in the UK, which is about 3.5% of all pregnancies. Evidence based guidelines published in 2008 recommend using an abnormal result from an oral glucose tolerance test to make the diagnosis. Before this recommendation there was a large variation in regional practices across the UK, in the screening, diagnosis, and management of gestational diabetes.

Previously, a borderline diagnosis of “impaired glucose tolerance of pregnancy” was recognised (defined as a blood glucose of 7.8-11.1 mmol/l after an oral glucose tolerance test) but not universally treated. In 2005, the Australian Carbohydrate Intolerance Study (ACHOIS) showed that women with impaired glucose tolerance of pregnancy randomised to treatment (dietary advice, home monitoring, and insulin if required) had an improved outcome compared with those randomised to routine obstetric care. In the treated group there was a 1% incidence of serious perinatal outcomes, compared with 4% in the untreated group.

As a result it is now recommended that women are either diagnosed as having gestational diabetes (which includes those previously diagnosed as having impaired glucose tolerance of pregnancy) and treated accordingly, or reassured that their glucose tolerance is currently normal.

Screening

All women should be screened for the risk factors for gestational diabetes at booking. These include:
Body mass index (BMI) over 30
Previous macrosomic baby weighing 4.5 kg or above
Previous gestational diabetes
First degree relative with diabetes
Family origin with a high prevalence of diabetes (South Asian, Caribbean, or Middle Eastern).

Women with one or more risk factor should be screened for gestational diabetes with an oral glucose tolerance test at 24-28 weeks.
In women who have previously had gestational diabetes, screening should start early, with an oral glucose tolerance test at 16-18 weeks. If this is negative, you should repeat it at 28 weeks. Alternatively you might offer such women home blood glucose monitoring to start as soon as their pregnancy is confirmed.


In gestational diabetes there is an increased incidence of:
Babies with macrosomia, which may lead to a difficult delivery
Induction of labour
Caesarean section (elective and emergency)
Neonatal hypoglycaemia
Perinatal death.
The incidence of these adverse events can be reduced by good glycaemic control.
Risk to pregnancy

Pregnant women with gestational diabetes

Initial management
You should refer women diagnosed with gestational diabetes to a specialist clinic. Here they can receive expert advice about the implications of the diabetes for themselves and their pregnancy from a multidisciplinary team. Women need initial advice about diet, managing their weight, and exercise and to be taught how to check their blood sugars. Patients should record at least four values a day; prebreakfast and one hour after each meal.

Glucose targets should be set individually, but reasonable starting values would be around 3.5-5.9 mmol/l for fasting glucose (prebreakfast) and less than 7.8 mmol/l one hour after a meal.
The specialist team will usually discuss the options for fetal growth surveillance and delivery with the patient, as well as the risk of postnatal diabetes and the implications for surveillance and future pregnancies.

Diet

Women should aim to reduce postprandial hyperglycaemia by changing their carbohydrates to those with a low glycaemic index (eg whole grain bread) and increasing their fibre intake to reduce peaks in blood glucose. However, it can be difficult to achieve acceptable postprandial glucose, especially after breakfast, without risking hypoglycaemia. It may therefore be necessary to find a compromise level of treatment.

Weight loss

You should advise women with gestational diabetes and a BMI over 27 to consider adopting a calorie restriction diet of 25 kcal/kg/day.
In a 90 kg woman this would result in a restriction to 2250 kcal/day. This has been shown to improve glycaemic control with no increased risk of ketonuria.


Exercise
Women should be advised about the safety and benefits of exercising.
Evidence based guidelines recommend 30 minutes of moderate exercise a day.
You can reassure pregnant women that moderate exercise is safe in all trimesters of pregnancy

Hypoglycaemic therapy

After two weeks of lifestyle changes and home blood glucose monitoring you should review the patient’s glycaemic control. If they have not achieved glycaemic targets you should start hypoglycaemic drugs such as metformin or glibenclamide (after the first trimester), or rapid acting insulin analogues (such as aspart or lispro), or both. You should individualise the choice of hypoglycaemic agent depending on the woman’s glycaemic profile. In patients with markedly raised blood sugars, insulin is the preferred treatment because it will be difficult to achieve adequate control with oral hypoglycaemic drugs.

Metformin is now approved in national guidelines for treating women with gestational diabetes.
Metformin has the following advantages over insulin and glibenclamide:
It is not associated with hypoglycaemia
It promotes weight loss in the first six weeks postpartum .It is well tolerated by patients.

The Metformin in Gestational Diabetes (MiG) trial found no difference in perinatal outcomes when comparing 751 women with gestational diabetes treated initially with insulin or metformin, although 46% of the metformin group had insulin added to achieve hypoglycaemic targets.6 Notably, the women for whom insulin was added gained less weight and had lower insulin requirements than the women who were allocated to insulin alone.

Glibenclamide can be used from 11 weeks’ gestation, which is after organogenesis is complete. The largest study on glibenclamide in gestational diabetes involved 404 women randomly assigned to either insulin or glibenclamide. In this study only eight women treated with the oral drug needed additional insulin, and perinatal outcomes were not significantly different. This study involved a mainly Hispanic population.

National guidelines support the use of metformin and glibenclamide in pregnancy to treat gestational diabetes following a systematic review of all trial data.3 Metformin crosses the placenta, while glibenclamide does not. Data from observational studies suggest metformin and glibenclamide do not have any teratogenic effects, but there are no large randomised control trials of their use in early pregnancy.

But as there are more data from the use of metformin to treat women with polycystic ovary syndrome (many of whom became pregnant while taking the drug), this is recommended in earlier pregnancy in preference to glibenclamide.
Gestational diabetes is generally diagnosed in the second trimester after organogenesis is complete.


Insulin is generally well accepted by women if needed to achieve glycaemic control.
National guidelines advocate the use of short acting insulin analogues (insulin aspart, or insulin lispro, or both).
These tend to be better than human insulin because they are associated with fewer hypoglycaemic episodes.

Antenatal monitoring and delivery

Antenatal monitoring and delivery in women with gestational diabetes is the same in women with diabetes diagnosed before pregnancy, and outlined later in this module.

Postnatal care

Immediately after delivery, women with gestational diabetes should stop all hypoglycaemic medications. You should offer a blood glucose check before discharge, and advise on the symptoms of hyperglycaemia.
At six weeks after the birth you should check fasting blood glucose to determine a return to normal glucose homoeostasis.

Even if the fasting blood glucose is normal annual testing is recommended, because women with gestational diabetes have a 2.6-70% lifetime risk of developing type 2 diabetes. Women should be advised about healthy lifestyle choices, including weight management and exercise, to reduce the risk of developing type 2 diabetes.

You should advise these women that they are at risk of developing gestational diabetes in future pregnancies.
They should tell their midwife as soon as pregnancy is confirmed, so they can be referred early for home blood glucose monitoring or offered an early glucose tolerance test.

Pregnant women with pre-existing (pregestational) type 1 or type 2 diabetes

There are 1800 (0.3%) and 1200 (0.2%) pregnancies complicated by type 1 and 2 diabetes, respectively, in England each year. There is no difference between type 1 and type 2 diabetes in obstetric outcome, as measured by perinatal mortality or incidence of shoulder dystocia.

Organogenesis occurs during the first 12 weeks of gestation and hyperglycaemia is teratogenic, so you should aim to achieve good glycaemic control before conception. There is a threefold increase in cardiac and neural tube defects in diabetic pregnancies. These organs form before the sixth week of gestation, which is before most women realise that they are pregnant.


An HbA1c level over 10% has been shown to be associated with a 35% risk of congenital malformations and an increased miscarriage rate.
You should advise women to avoid pregnancy until their glycosylated haemoglobin levels have fallen. You should offer women monthly HbA1c measurements before conception to monitor their control.

Women should aim to achieve an HbA1c level below 6.1% if safely achievable.

This value is recommended in evidence based guidelines because it is associated with the lowest incidence of congenital malformation. Women should be advised it minimises but does not eliminate all the risks.

This target will not always be safely achievable, particularly without unacceptable levels of hypoglycaemia. Also, it may be difficult to maintain an HbA1c level of <6.1% until pregnancy is achieved. Clinicians should support women in their attempts to achieve tight control, but compromise HbA1c values may need to be agreed. Before the NICE guidelines, the accepted level many clinicians used was <7%.

Prepregnancy counselling and care

CEMACH reported only 17% of UK diabetic units in 2002-3 were able to offer prepregnancy counselling that was structured and multidisciplinary; and only 35% of patients achieving pregnancy had documented prepregnancy counselling.

At every consultation you should ask every woman with diabetes who is of childbearing age whether she is planning a pregnancy. If she is, you should refer her for specialist advice. If not, you should advise her to use effective contraception.
Advice should include glycaemic control and targets, medication review, complication screening and management, delivery, and postnatal care.

Medication review

The CEMACH report found that only 39% of patients with diabetes were taking folic acid at either standard or high dose before conception. The uptake was higher in patients with type 1 diabetes than in those with type 2 diabetes (42% compared with 29%).
You should ensure that patients start folic acid at a high dose (5 mg not 400 µg daily) ideally at least three months before conception, and continued until the end of the first trimester.

You should review oral hypoglycaemic agents and convert to insulin therapy if necessary, and stop any teratogenic medication (such as statins) and fetotoxic agents (such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB)) while the patient is trying to conceive.

Preventing and managing complications

Diabetic nephropathy
You should check for microalbuminuria in all women with diabetes during prepregnancy counselling.
Pregnancy per se in women with diabetes is not associated with the development of nephropathy. It is associated with the progression of nephropathy, if moderate to advanced nephropathy is present. This may then progress to end stage renal failure.

Those with significant renal impairment (serum creatinine >120 μmol/l or estimated glomerular filtration rate (eGFR) <45) should be referred to
arenal physician before stopping contraception. They can advise on the risks and benefits of stopping ACE inhibitors or ARBs as soon as conception is confirmed as opposed to before conception.

However, diabetic nephropathy is associated with an increased risk of adverse pregnancy outcomes, including fetal growth restriction, chronic hypertension, pre-eclampsia, and preterm birth.
Development of pre-eclampsia has been found to be markedly increased (about sevenfold more) in pregnant women with diabetic nephropathy.

So you should offer these women low dose aspirin as prophylaxis against pre-eclampsia. If proteinuria is greater than 3 g/day you should start thromboprophylaxis with low molecular weight heparin. You should not use eGFR in pregnant women to monitor renal function because it underestimates glomerular filtration rate (GFR). This is because the blood flow through the kidney increases dramatically, up to 80% in pregnancy. Therefore, GFR increases and creatinine clearance rises by 50% leading to a fall in serum creatinine. As the eGFR is based on serum creatinine this is no longer an accurate measure of the GFR.

Diabetic retinopathy

At the first appointment for pre-pregnancy counselling you should offer digital retinal assessment to all women with diabetes.
Rapid optimisation of glycaemic control should be avoided before pregnancy until after retinal assessment or treatment is undertaken.
This is because, paradoxically, tighter control is associated with progression (usually temporary) of retinopathy. If a woman with known retinopathy presents already pregnant the benefits to the fetus of rapid glycaemic control outweigh the risk of visual deterioration to the mother.

Once pregnant, you should ensure retinal screening is arranged at the first antenatal appointment and, if normal, at 28 weeks. If retinopathy is present women should be rescreened at 16-20 weeks and followed up six months postpartum.
Laser treatment can be performed during pregnancy, and retinopathy is not a contraindication for vaginal delivery.

Hypertension

If the patient is taking drugs for hypertension you should change teratogenic and fetotoxic medication to those recognised as safe in pregnancy, such as labetalol, methyldopa, a calcium antagonist
(slow release nifedipine, amlodipine), or an alpha adrenergic blocker (doxazosin).


Antenatal care
Antenatal monitoring for women with gestational or pregestational diabetes is similar. Ideally it should be undertaken jointly by a diabetologist and obstetrician, supported by specialist nurses and midwives.
Booking should be early; before 10 weeks is optimal. You should ensure that patients have regular reviews (typically every two weeks) to assess glycaemic control, as well as blood pressure and urinalysis (because of the increased risk of pre-eclampsia).

Achieving glycaemic control in pregnancy

Type 1 diabetes
Methods of achieving tight glycaemic control vary from patient to patient. In the first trimester insulin requirements may fall. At 18-20 weeks insulin requirements start to increase. They reach, on average, an increase of 40% by term. Women should have the opportunity to consult a dietitian if not already undertaken before pregnancy.

A basal bolus regimen is the preferred treatment because it gives tighter control and patients have greater flexibility compared with regimens using premixed insulins. Rapid acting insulin analogues (aspart, lispro) are superior to regular soluble insulins because they are associated with fewer hypoglycaemic episodes, and, in general, patients prefer them.

NICE recommends that you use isophane as the longer acting insulin because it has more safety data than other preparations. The longer acting insulin analogues, detemir and glargine, have been used in pregnancy and observational data suggest that there is no difference in fetal outcome. When a patient is already established on detemir or glargine, they should be counselled about the risks and benefits of continuing on these insulins.
Target glucose levels should be determined individually for each patient, but starting points for determining targets are given in Table 2.

Table 2. Blood glucose targets for type 1 diabetes

Fasting
One hour post meal
Blood glucose
3.5-5.9 mmol/l
<7.8 mmol/l
• If patients have disabling hypoglycaemia episodes, continuous subcutaneous insulin infusion (pump therapy) can be offered by centres with the relevant expertise.


Type 2 diabetes
Management of type 2 diabetes in pregnancy has changed following the NICE guidelines. Previously, all women with type 2 diabetes had their oral hypoglycaemic drugs stopped, ideally before pregnancy, and were started on insulin.
NICE guidelines state that metformin can be used as an adjunct or alternative to insulin in the preconception period and during pregnancy, when the likely benefits from improved glycaemic control outweigh the potential for harm.

Metformin has long been used in early pregnancy as it is used to promote fertility in women with polycystic ovary syndrome. Several studies have shown that metformin exposure in the first trimester is not associated with an increase risk of major congenital malformations.
You should document that women who choose to continue with metformin have given informed consent because it is not currently licensed for use in pregnancy in the UK, although the British National Formulary now states it can be used in pregnancy. All other oral hypoglycaemic agents should be stopped before pregnancy and insulin substituted if required.

Table 3. Blood glucose targets in type 2 diabetes

Fasting
One hour post meal
Blood glucose
3.5-5.9 mmol/l
<7.8 mmol/l
• Insulin regimens should be individualised as for type 1 diabetes, but starting points for determining individualised targets are given in Table 3.

Diabetes ketoacidosis

Hyperemesis puts women with type 1 diabetes at a higher than usual risk of developing diabetic ketoacidosis, which is associated with fetal death.
Because of the risks to the pregnancy, you should admit any pregnant patient with type 1 diabetes who becomes unwell and develops vomiting and has blood glucose above target levels. Pregnant women are susceptible to euglycaemic acidosis, and the fetus is very sensitive to ketotic states.

Admission should preferably be to a level 2 critical care bed for obstetric and medical care.
Many patients now have home ketone monitors, which operate on principles similar to home blood glucose monitors. National guidelines recommend that all women should be offered ketone monitoring equipment and advised to test if they become unwell, and seek medical advice.


Hypoglycaemia unawareness
Hypoglycaemia unawareness occurs when patients are unable to mount a sympathetic nervous system response to their blood sugars becoming low. Early pregnancy is associated with an increased frequency of hypoglycaemia, with a peak incidence between 10 and 15 weeks. Contributing factors include striving to achieve tight glycaemic control, hyperemesis, and an impairment of counter-regulatory hormonal systems.

Frequent episodes of hypoglycaemia may lead to reduced warning signs and this should be discussed with each patient. It is good practice to offer glucose solutions and glucagon pens, and instruct patients’ partners on how to use them. National guidelines recommend that HbA1c targets should be pursued only if safely achievable.3 In a patient with hypoglycaemic unawareness, it may be necessary to set higher targets after discussion between the physician and the patient. Disabling hypoglycaemia is associated with road traffic accidents and death.

You should discuss safe driving (and document this discussion), and advise women to stop driving until a consultant or GP report shows they have regained hypoglycaemia awareness. They must also tell the Driver Vehicle and Licensing Agency (DVLA). You should advise women who have regained hypoglycaemia awareness to check their blood glucose before driving.

Fetal monitoring

Fetal growth is assessed by ultrasound scans at 28, 32, and 36 weeks. These scans will assess the amniotic fluid volume and look for macrosomia, in particular looking at the abdominal circumference.
Increase in abdominal circumference can be an indication of poor glycaemic control and efforts will be made to improve glycaemic control. Growth may still accelerate despite good glycaemic control and there is evidence that this is influenced by periconceptional glycaemic control.

There are two types of macrosomia:

Symmetric – an overall large baby, which can be associated with trauma during birth
Asymmetric - where the abdominal circumference is relatively larger than the head size. This may put the baby at risk of developing shoulder dystocia if delivered vaginally.
As well as routine anomaly screening, women with pregestational diabetes should be offered a specialist scan of the fetal heart at 20 weeks because of the increased risk of fetal anomalies.

Labour

Neonatal hypoglycaemia requiring intervention is reduced if the woman maintains her blood glucose between 4 mmol/l and 7 mmol/l during labour. This can be achieved by using either an insulin sliding scale or continuing the woman’s normal insulin or oral hypoglycaemic regimen.

Delivery

The obstetrician will use all the information gained from antenatal care when discussing each woman’s birthing plan. National guidelines advise obstetricians to offer elective delivery after 38 weeks either by induction of labour or caesarean section to all women with diabetes (gestational, type 1, and type 2) who have normally grown fetuses.


Early delivery of a normally grown fetus in women with diabetes is indicated because of the increased incidence of stillbirths, especially late stillbirths in these women. CEMACH found that in diabetic pregnancies the incidence of stillbirth was raised, from a national stillbirth rate of 5.7 per 1000 births to 26.8 stillbirths per 1000 births. Some 27% of these stillbirths in women with diabetes occurred after 37 weeks’ gestation. There was no significant difference in rates between type 1 and 2 diabetes.

Due to this increased risk of late intrauterine death most maternity units will recommend delivery at the latest by 39 weeks. Tests of fetal wellbeing have a low predictive value apart from in those women at high risk of intrauterine growth restriction.
Women with a macrosomic fetus need to be counselled about the increased risk of obstructed labour, and particularly shoulder dystocia with vaginal delivery. Fetal growth scans can also pick up intrauterine growth restriction, which may necessitate early delivery.

CEMACH reported that 36% of patients with diabetes had a preterm delivery and 67% had a caesarean section, compared with 7% and 22%, respectively, in the general population. Diabetes in itself is not a contraindication for vaginal delivery or for vaginal delivery after a previous caesarean section.

Neonatal care

Newborns of women with diabetes are at risk of hypoglycaemia after delivery, a consequence of relative maternal hyperglycaemia and fetal hyperinsulinaemia. You should ensure that mothers are made aware of this possibility before delivery.
The baby should stay with the mother unless there is a medical indication for admission to the neonatal unit.

Women should feed their babies, ideally, within 30 minutes of giving birth and then at frequent intervals. The neonate should not have a blood glucose level taken until two to four hours after delivery unless it is showing signs of hypoglycaemia. Admission to neonatal intensive care may be necessary for intravenous dextrose and monitoring if the baby has difficulty feeding or signs or hypoglycaemia with abnormal signs. These include:
Jitteriness ,Irritability ,Seizures ,Poor tone.
Other indications for transfer to neonatal intensive care include respiratory distress, jaundice, cardiac decompensation, or gestation of less than 34 weeks.

Postnatal care

Women with any type of diabetes should be offered a minimum stay of 24 hours in hospital so that the baby can be monitored and be shown to maintain their blood glucose and feed well.
Mothers with diabetes should have a documented plan for glycaemic control as part of their birthing plan so that during and after delivery everyone is aware of the need (or not) for a sliding scale, with or without basal insulin and so on. Insulin doses will need to be reduced immediately after delivery to prepregnancy levels.

Insulin levels may need to be reduced below prepregnancy levels if the mother decides to breast feed. Women with type 1 diabetes who were controlled prepregnancy on twice daily mixed insulin and converted onto a basal bolus regimen may prefer to continue the basal bolus regimen at a lower dose post delivery.


Those with type 2 diabetes previously controlled with oral medication alone can revert back to oral medication, providing it is compatible with breast feeding. You should encourage women with diabetes to breast feed. Breast feeding helps protect the infant against infections, asthma, eczema, and obesity. Women should have carbohydrates available before and during breast feeding.

Women with type 2 diabetes can continue metformin or glibenclamide while breast feeding but no other oral hypoglycaemic medications.
Before discharge it is imperative to advise all women with diabetes about the importance of contraception and to advise attendance at a prepregnancy clinic before the next pregnancy to ensure they have a full medical review.

National guidelines on gestational diabetes advise performing an oral glucose tolerance test screening if any of the following risk factors are present:
• BMI over 30
• Previous macrosomic baby weighing over 4.5 kg
• Previous gestational diabetes
• First degree relative with diabetes
• South Asian, black Caribbean, or Middle Eastern origin

Glycosuria in pregnancy is common because the renal tubular threshold for glucose falls in pregnancy. Most women have glycosuria at some point in their pregnancy and in the context of normal growth it is not worrying.

National guidelines now support the use of metformin throughout pregnancy, but not pioglitazone. If the patient does not achieve tight glycaemic control using a maximum dose of metformin and lifestyle changes, she may need to start insulin. If insulin is added now before she tries the higher dose metformin, she could gain more weight, which is associated with reduced fertility.

There are few data on pioglitazone in pregnancy, but there is limited evidence to suggest that it is associated with postimplantation fetal losses, delayed development, and reduced fetal weight.18 So you should stop her pioglitazone and increase her metformin.
A systematic review found metformin to be safe in pregnancy.
Metformin crosses the placenta, but observational data have not shown any teratogenic effects.

Retinopathy can deteriorate in pregnancy, but she has mild retinopathy and a short duration of diabetes. The chance of her retinopathy progressing is small and should not be a contraindication for pregnancy.


• This woman is 42 so her chance of conceiving is reduced due to her age. A delay of a year will reduce her age related fertility further. Prepregnancy counselling should be a supportive process, and if you wanted to take this approach monthly reviews would be better. In view of her age and reducing fertility, you should encourage her to gain tight control rapidly so that her HbA1c ideally comes down before attempting to conceive.

Hypoglycaemia unawareness is a common problem in pregnancy. The DVLA medical rules clearly state that if a patient develops impaired hypoglycaemic awareness or disabling hypoglycaemia while at the wheel they must inform the authority and stop driving until they regain hypoglycaemia awareness (documented by a medical report). A consultant or GP must write the report because having your driving licence removed is a disruptive life event.

You should advise all patients with diabetes to carry glucose with them. This patient has hypoglycaemic unawareness; even if she carries glucose with her she will not realise that she needs to take it, unless she undertakes frequent home monitoring of blood glucose. You could be negligent if you do not advise her to stop driving, so it would be sensible to record that you told her this.

This does not address the problem of a patient driving with hypoglycaemia. All patients with type 1 diabetes who are pregnant should have a glucagon pen. The whole family should be familiar with how to inject glucagon because they will be giving it if the patient has a severe hypoglycaemic event

It is likely that it will improve during pregnancy, but this does not address the driving issue and she must stop driving. During the first trimester there is an increased frequency of hypoglycaemia, with a peak incidence between 10 and 15 weeks. Some contributing factors are tight glycaemia control and an impairment of counter-regulatory hormonal systems.

Pregnant women with diabetes have an increased risk of complications during delivery and labour. There is an increased incidence of perinatal death in newborns born to mothers with diabetes. Evidence shows that women who have maternal hyperglycaemia during labour have a higher incidence of fetal distress and fetal hypoglycaemia.19 These women need close monitoring and prompt intervention, which would not be possible outside of a hospital environment

Pregnant women with diabetes do not automatically need a caesarean section.

Her fetus is not macrosomic on ultrasound scanning so there is no medical indication for a caesarean section. She should discuss the method of delivery with her obstetrician

It is better for her to have a hospital birth because of the risks associated with labour and delivery in women with type 2 diabetes. She does not necessarily need to be attached to an intravenous insulin infusion. CEMACH found that women were being put on sliding scales unnecessarily during labour.2 Such sliding scales were often poorly managed with suboptimal monitoring of blood glucose leading to hypoglycaemia.

During labour the patient should aim to keep blood glucose between 4 mmol/l and 7 mmol/l. Women can maintain control of their diabetes with multiple dose injections, leading to greater mobility in labour. You should consider a sliding scale for mothers with type 1 diabetes and in any patient whose blood glucose is not maintained between 4 mmol/l and 7 mmol/l.

There is an increased risk of a neonate born to a diabetic mother becoming hypoglycaemic within the first 24 hours after birth. Maternal hyperglycaemia causes fetal hyperinsulinaemia. After delivery this excess production of insulin in the neonate can lead to hypoglycaemia. This can be reduced by tight glycaemic control during labour and feeding the baby within the first half hour after birth.


Women become more insulin resistant during pregnancy due to placental production of hormones including human placental lactogen and cortisol. You should be able to control her diabetes on her prepregnancy regimen once the placenta is delivered. Because she was not on insulin before she became pregnant and she is breast feeding, she should maintain euglycaemia on metformin alone before becoming pregnant she was controlled on metformin alone, so this should be sufficient to control her diabetes post delivery.

National guidelines now support the use of metformin during breast feeding because less than 0.3% passes into the breast milk, and conclude from this that it is safe to use.
The BNF endorses its use in breast feeding.
Both metformin and glibenclamide are compatible with breast feeding, which you should encourage.