Section 1 – Holly

Holly is a 31-year-old lady who is now 26 weeks into her first pregnancy. She sees you with a 3-day history of dysuria and frequency of micturition. There is no history of abdominal pain or fever.

A urine dipstick reveals a positive test for nitrites and the presence of white cells. It also shows glycosuria ++.

What is your assessment of Holly’s situation?

Section 2

Holly appears to have a lower urinary tract infection (UTI). The glycosuria suggests she may have gestational diabetes (GDM), although it is possible she may have entered the pregnancy with undiagnosed type 2 diabetes.

What factors would you look for in Holly’s history that could suggest she is at high risk of gestational diabetes?

Section 3

Risk factors for developing GDM include (NICE, 2020):

• BMI >30 kg/m²_.
• Previous GDM.
• Previous macrosomic baby weighing 4.5 kg or more.
• Family history of diabetes (first-degree relative).
• Ethnic background with high prevalence of diabetes (South or East Asian, African–Caribbean, Middle Eastern).

 
Further considerations regarding the likelihood of GDM include advanced maternal age (>35 years), a history of polycystic ovarian syndrome (a condition of increased insulin resistance) and previous unexplained fetal death.

Holly had a pre-pregnancy BMI of 29.4 kg/m² but no family history of type 2 diabetes.

What action would you take?

Section 4

In addition to treating the UTI, Holly needs to be investigated for possible GDM.

Holly is prescribed a course of cephalexin (a safe and effective antibiotic in pregnancy) and encouraged to drink plenty of fluids. A mid-stream urine sample is sent off for laboratory analysis. A fingerprick glucose reading demonstrates a glucose level of 11.7 mmol/L. A blood sample is sent off for HbA_1c assessment (HbA_1c will not accurately reflect recent onset of diabetes in a pregnancy but could point toward the likelihood of pre-existing undiagnosed type 2 diabetes when entering the pregnancy).

NICE (2020) recommends formal testing for GDM if pregnant women have:

• Glycosuria of ++ or above on one occasion.
• Glycosuria of + or above on more than one occasion.

 
In Holly’s case, local maternity services are contacted and an oral glucose tolerance test (OGTT) is arranged to ascertain the diagnosis of GDM. In the meantime, the importance of controlling blood glucose levels in pregnancy is explained to her and she is advised on eating a healthy diet and taking exercise to help achieve this.

Can you explain why gestational diabetes arises?

Section 5

GDM is defined as diabetes diagnosed during the second and third trimester of pregnancy that was not clearly overt diabetes prior to gestation (ElSayed et al, 2023). As pregnancy progresses, insulin resistance rises and this is normally countered by increasing insulin production. However, women with GDM inherently have a greater degree of insulin resistance compared to those without GDM, and this coupled with reduced beta-cell capacity to produce the required insulin response leads to maternal hyperglycaemia (Catalano, 2014).

GDM is a more common cause of diabetes in pregnancy than pre-existing diabetes, accounting for nearly 90% of cases, and the prevalence is increasing in line with the demographic rise in body mass index (Noctor and Dunne, 2017).

Why is it important to identify gestational diabetes?

Section 6

Maternal hyperglycaemia from poorly controlled GDM leads to fetal macrosomia. The consequence at delivery is an increased risk of obstructed delivery from shoulder dystocia, clavicular fracture and brachial plexus injury (Melzer, 2010).

Fetal hyperglycaemia is associated with a rise in congenital abnormalities. The incidence of neonatal respiratory distress, meconium aspiration and jaundice are all raised following GDM, and the carry-over of fetal hyperinsulinaemia post-delivery can lead to neonatal hypoglycaemia. All of the above are common reasons for admission to the neonatal intensive care unit (Noctor and Dunne, 2017).

For the mother with GDM, the incidence of pre-eclampsia, polyhydramnios, pre- and post-partum haemorrhage, and infection are all increased. Failure to progress with labour and delivery by caesarean section are more frequent with pregnancy complicated by GDM (Noctor and Dunne, 2017).

In the longer term, there is an association between offspring exposed to in utero GDM and the later occurrence of obesity and glucose intolerance (Silverman et al, 1998). Women who have had GDM are at increased risk of developing type 2 diabetes (Bellamy et al, 2009).

It is important, therefore, that primary and community care practitioners can appropriately advise women at high risk of GDM, understand the management of GDM and, as indicated later in this case study, assume responsibility for post-pregnancy follow-up of GDM (McGovern et al, 2014).

What treatments for diabetes are considered safe and effective in gestational diabetes?

Section 7

Whilst the joint diabetes and antenatal clinic will assume responsibility for the majority of treatment decisions, primary healthcare workers need to be aware of GDM management. Effective treatment of GDM has been demonstrated to reduce fetal macrosomia, fetal and maternal birth trauma, and perinatal death (Horvath et al, 2010).

Lifestyle change constitutes the first-line treatment of GDM. NICE advises that a trial of diet and exercise should be offered to women with GDM without complications who have a fasting plasma glucose (FPG) level below 7 mmol/L at diagnosis (NICE, 2020). If dietary change and physical exercise prove ineffective in achieving blood glucose targets within 1–2 weeks, medical treatment should be commenced. In the absence of contraindications, this would usually be metformin.

For those women with an FPG of 7 mmol/L or above at diagnosis, and for women with an FPG of 6.0–6.9 mmol/L who have a complication such as fetal macrosomia or hydramnios, immediate medical treatment with insulin (with or without metformin), alongside lifestyle measures, is recommended (NICE, 2020).

Metformin, although not licensed for use in pregnancy, is considered safe and has gained ground as an option for treating GDM when lifestyle measures are insufficient. The risk of perinatal complications appears to be no higher than in insulin-treated patients (Rowan et al, 2008) and there is the advantage of less weight gain, less monitoring and reduced risk of hypoglycaemia in comparison to insulin (Iftakhar, 2012). Should gastrointestinal side effects prove troublesome with metformin, the modified-release preparation may be tried. However, if glycaemic control is inadequate then insulin should be promptly initiated.

Insulin therapy has traditionally been regarded as the first-line medical treatment in GDM and remains the preferred treatment of the American Diabetes Association (ElSayed et al, 2022b). Often a basal–bolus insulin regimen will be required, and insulin doses can be adjusted on a frequent basis, noting that requirements are likely to rise as pregnancy progresses, reflecting increasing insulin resistance. The rapid-acting insulin analogues (e.g. insulin aspart and insulin lispro) offer advantages in improved glycaemic control and reduced hypoglycaemia compared with human soluble insulins (NICE, 2020).

Section 8

Holly’s OGTT revealed an FPG of 6.7 mmol/L and a 2-hour plasma glucose of 9.4 mmol/L, confirming the diagnosis of GDM (thresholds for diagnosis: either FPG ≥5.6 mmol/L or 2-hour plasma glucose ≥7.8 mmol/L), and she was reviewed in the joint diabetes and antenatal clinic.

The need to carefully control blood glucose levels was explained to Holly and she was offered lifestyle advice, instructed on glucose monitoring, referred to a dietitian and subsequently commenced on metformin.

What frequency of glucose monitoring should be advised for Holly, who is using metformin for her gestational diabetes?

Section 9

Holly, as a person using oral medication to control GDM, should be encouraged to take fasting and 1-hour post-meal readings to guide treatment. This monitoring pattern would also be appropriate for those on dietary control alone and if insulin is administered as a basal injection alone.

Section 10 – Nadia

Nadia is a 34-year-old lady of Indian ethnic origin who is now 24 weeks into her second pregnancy, her last pregnancy being 7 years ago. Nadia’s BMI is 32.4 kg/m² and her father has type 2 diabetes. GDM was not, however, diagnosed during her first pregnancy and her first baby was born at term weighing 3.8 kg.

How would you assess Nadia’s risk of acquiring gestational diabetes?

Section 11

Nadia’s ethnic origin, obesity and family history of type 2 diabetes place her at high risk of GDM.

These risk factors were identified by the midwives at booking, and Nadia is scheduled for an OGTT at 28 weeks’ gestation.

There are conflicting recommendations over screening arrangements and diagnostic criteria for GDM. NICE (2020) recommends an OGTT between 24 and 28 weeks’ gestation for those at high risk of GDM (or as soon as possible after booking if previous GDM), with the following diagnostic criteria:

• Fasting plasma glucose of 5.6 mmol/L or more.
• 2-hour plasma glucose of 7.8 mmol/L or more.

 
The American Diabetes Association now recommends screening for diabetes (with an HbA_1c or fasting plasma glucose test) in those women with risk factors who are planning a pregnancy, so that those found to have diabetes can optimise their glucose control ahead of pregnancy (ElSayed et al, 2022a).

Section 12

A diagnosis of GDM is made from Nadia’s OGTT (FPG 8.1 mmol/L; 2-hour plasma glucose 12.7 mmol/L). Nadia is accordingly referred to the joint diabetes and antenatal clinic.

Nadia is quickly established on a basal–bolus insulin regimen of Lantus and NovoRapid in the diabetes/antenatal clinic, provided with a meter to self-monitor her capillary glucose and set targets for glycaemic control. NovoRapid is licensed for use in pregnancy and the SmPC of Lantus advises that Lantus may be considered during pregnancy if clinically needed.

What frequency of glucose monitoring might you expect Nadia to undertake?

Section 13

Intensive glucose monitoring is advised during a pregnancy affected by diabetes, and you should be prepared to issue more glucose test strips. For Nadia, on a basal–bolus insulin regimen, NICE (2020) recommends capillary blood glucose monitoring prior to meals (including fasting), 1-hour post-meals and before bedtime.

NICE (2020) recommends setting the same capillary plasma glucose target levels for women with GDM as for those with pre-existing diabetes. Thus, ideal glucose targets would be the following:

• Fasting: 5.3 mmol/L.
• 1 hour after meals: 7.8 mmol/L; or 2 hours after meals: 6.4 mmol/L.

 
In practice, targets will need to be individualised, recognising the need to avoid problematic hypoglycaemia. In the case of women using insulin, such as Nadia, capillary glucose levels should be kept above 4 mmol/L. Women at risk of hypoglycaemia should be advised to carry a fast-acting form of glucose at all times.

It should be mentioned that continuous subcutaneous insulin infusion (an insulin pump) is an alternative to a basal–bolus insulin regimen for pregnant women who do not achieve adequate glucose control without troublesome hypoglycaemia. Real-time or intermittently scanned (flash) glucose monitoring is an option where there is severe hypoglycaemia (especially if there is hypoglycaemia unawareness) or where unstable glucose readings are problematic (NICE, 2020).

What role does primary care have in managing women with gestational diabetes?

Section 14

Whilst management of GDM will primarily occur in the diabetes/antenatal clinic, women with GDM may, in addition to the usual pregnancy-related health issues, need support from practice nurses and GPs in blood glucose monitoring and interpretation, and reassurance that maintaining good glycaemic control will improve outcomes for their babies and themselves. Advice regarding medication use and side-effects, and in particular the recognition and treatment of hypoglycaemia for those using insulin, may be necessary.

Nadia is frequently reviewed in the diabetes/antenatal clinic and achieves satisfactory glycaemic control with her insulin regimen. She delivers a healthy girl at 39 weeks’ gestation without significant problems. Nadia’s insulin is stopped after delivery and glucose levels are checked and seen to be running below 10 mmol/L. It is also important to check baby’s glucose levels, as there is a risk of neonatal hypoglycaemia.

How should Nadia’s glucose control be assessed in the post-partum period?

Section 15

Whilst diabetes medications used for GDM are usually stopped at delivery in the expectation that glucose levels will fall to pre-pregnancy levels, there is the possibility that hyperglycaemia will persist (and hence the need for glucose checks immediately following delivery).

Nadia should have a formal test for hyperglycaemia within 3 months of delivery, and there needs to be clarity as to who assumes responsibility for this.

NICE (2020) advises that women with GDM (whose blood glucose levels return to normal after delivery) should be offered a fasting plasma glucose (FPG) test at 6–13 weeks postpartum to exclude diabetes (pragmatically, this could be at the 6-week postnatal review); otherwise, beyond 13 weeks postpartum, an HbA_1c test can be offered.

• If FPG is ≥7.0 mmol/L or HbA_1c is ≥48 mmol/mol, a confirmatory test for type 2 diabetes should be carried out and type 2 diabetes pathways (NICE, 2022) should then be followed.
• If FPG is 6.0–6.9 mmol/L or HbA_1c is 39–47 mmol/mol, there is a high risk of developing type 2 diabetes. Lifestyle advice and an offer to refer to the NHS Diabetes Prevention Programme should follow.
• If FPG is <6.0 mmol/L or HbA_1c is <39 mmol/mol, reinforce lifestyle measures and perform annual HbA_1c checks.
  • Note these are different HbA_1c risk thresholds than for “prediabetes” in the NICE (2017) PH38 advice, because they refer to a different population.

Nadia has an FPG test at 6 weeks post-delivery, which reveals an FPG <6.0 mmol/L, suggesting that she does not have prediabetes or type 2 diabetes.

What about Nadia’s future risk of developing type 2 diabetes?

Section 16

Nadia’s GDM is a marker for insulin resistance and places her at increased risk of developing prediabetes and type 2 diabetes in the future compared to women without GDM (relative risk 7.4; Bellamy et al, 2009). Nadia should be alerted to the likelihood of recurrence of GDM in future pregnancies and of the possibility of type 2 diabetes in the future.

Nadia sees you at the clinic following her normal FPG test and asks about her GDM and its future implications.

What advice would you offer Nadia for the future, and what arrangements would you set in place for future screening of diabetes?

Section 17

It is helpful to think that GDM confers “prediabetic status”. There is good evidence that lifestyle adjustment can prevent or delay the onset of diabetes (Knowler et al, 2002; Lindström et al, 2003). Encourage Nadia to be careful with her diet, take regular exercise and aim for weight loss – similar principles as for those with type 2 diabetes – as detailed in NICE public health guidance on prevention of type 2 diabetes (NICE, 2017). She is offered referral to the Healthier You NHS Diabetes Prevention Programme.

Nadia should be placed on annual recall, checking HbA_1c, lipids, renal function, weight and blood pressure.

With her history of GDM, in any future pregnancy Nadia should be offered early self-monitoring of blood glucose or an OGTT as soon as possible after booking (NICE, 2020).

In reality, there is a disappointingly low rate of both short-term and longer-term review of GDM, with rates of both around 20% in one study (McGovern et al, 2014). Possible reasons for this poor follow-up include lack of awareness amongst women with GDM, poor communication between secondary and primary care, a lack of consensus over responsibility for post-natal tests and missed opportunities in primary care for the annual review.