Abstract
Gestational diabetes mellitus (GDM) is a common disease of pregnancy, affecting approximately 5% of pregnancies in the UK. It has serious health implications for both mother and baby which stretch beyond the antenatal period. Understanding how to recognise and mitigate some of the modifiable risk factors for GDM and its long-term sequelae is important for GPs.
Clinical case scenario 1
Mrs Kanathuri is a 32-year-old woman who is booked in with you for her post-natal check. She had an elective caesarean section at 38 + 4 for a ‘large for gestational age’ baby. She had a booking body mass index (BMI) of 29.43 kg/m2 and was diagnosed with gestational diabetes mellitus (GDM) at 27 weeks’ gestation. She has no other medical problems of note, and does not take any regular medications. She has stopped the metformin she was taking during her pregnancy.
Her GP takes care in the consultation to ensure that Mrs Kanathuri is aware of the long-term risks of GDM and counsels her on the importance of achieving a healthy weight. Mrs Kanathuri is booked in for her 6-week fasting blood glucose test and GDM is coded in her medical notes to ensure that she is recalled for an annual HbA1c. The GP also offers her referral to the National Diabetes Prevention Programme and signposts her to appropriate websites for further reading.
Gestational diabetes
GDM is a common problem, affecting at least 5% of pregnancies in the UK. It carries with it significant risks for both mother and baby, including pre-eclampsia, macrosomia, shoulder dystocia, increased risk of caesarean section, pre-term delivery, still birth, and neonatal hypoglycaemia and hyperbilirubinaemia (Kim, 2010). Notably, those with GDM have at least a seven-fold risk of developing type 2 diabetes (T2DM) later in life compared to those with a normoglycaemic pregnancy, and their children are at high risk of developing obesity and T2DM later in life (Vounzoulaki et al., 2020).
Despite these trajectories, women are often lost to follow up after delivery for a number of potential reasons including poor understanding, missed or inadequate communication, coding errors, or uncertainty over care ownership (Pierce et al., 2011). As the number of pregnancies complicated by GDM is likely to rise, in part due to increasing maternal age and rates of obesity, it is important that GPs understand and act on the long-term risks of GDM in primary care.
Pathophysiology
A number of complex factors contribute to the development of GDM (Fig. 1). The main problem is insulin resistance and pancreatic beta cell dysfunction. As a healthy pregnancy progresses, a woman’s body becomes increasingly insulin resistant in order to facilitate the maternal metabolic demands of pregnancy and to ensure that the growing foetus has sufficient glucose for healthy development. This happens due to a number of hormonal and metabolic changes in pregnancy with placental hormones such as human placental lactogen, which interferes with the action of insulin, partially responsible (Nien et al., 2007).
GDM is a complex condition with a variety of contributing factors.
In healthy individuals, pancreatic beta cells are able to compensate for this insulin resistance by increasing in number and productivity. This ensures adequate glucose removal from the blood, either through its storage as glycogen in the liver, or via uptake into adipose or muscle cells. In GDM, however, the pancreatic beta cells are not able to keep up with demand and blood glucose levels begin to rise. On delivery of the placenta the majority of insulin resistance is removed and most, although not all, women return to their euglycaemic prenatal state. Appropriate follow-up is important so people who go on to develop T2DM and associated metabolic dysfunction, are not missed.
Clinical case scenario 2
Miss Roberts, a 25-year-old woman, attends for her pill check. She has a BMI of 34 kg/m2 and polycystic ovary syndrome (PCOS). Her blood pressure is in the normal range. On enquiring about her sexual activity and sexual health screens, Miss Roberts tells her GP that she has been with her partner for 2 years and they are considering trying for a baby in the next year. The GP uses this opening as an opportunity to discuss the importance of trying to achieve a healthy BMI prior to conception, particularly as Miss Roberts is at a higher risk of developing GDM already, as she has PCOS. She also counsels her on the importance of perinatal folic acid supplementation. As Miss Roberts has a BMI over 30 kg/m2, a higher dose of folic acid (5 mg a day) is recommended for at least 3 months prior to conception until week 12 of pregnancy.
Obesity
Obesity reduces the effectiveness of insulin and impairs the liver’s ability to store glucose. This combination greatly increases the risk of hyperglycaemia which, when coupled with the metabolic demands of pregnancy and its progressively insulin resistant state, can move people from pre-existing insulin resistance into the diabetic range. It is therefore important to encourage women to aim for a healthy BMI (Table 1) before becoming pregnant and offer weight management advice and support in pre-conception discussions.
BMI ranges.
Caloric intake should only increase in the third trimester where an additional 200 kcal per day is required (Better Health; Start for Life (n.d.)).
Weight management
Many local authorities now provide free weight management programmes through GP referral or social prescribing services. There are a number of additional national weight management options available to patients including mobile applications, websites, charitable health programmes (e.g. the English Football League Trust FIT FANS), and the NHS Digital Weight Management Programme (Better Health; Let’s do this (n.d.)). Although some services require a GP referral, many of them allow self-referral by patients.
The National Institute for Health and Care Excellence (NICE) suggests considering pharmacological intervention only if lifestyle approaches have not been successful. Orlistat can be trialled in primary care where a patient has a BMI ≥30 kg/m2, or ≥28 kg/m2 with other risk factors including high blood pressure or high cholesterol (NICE, 2014). Orlistat should be discontinued if the patient has failed to lose ≥5% of their body weight over the first 3 months of use. Routine use in pregnancy is not recommended, and as such women of childbearing age should be counselled appropriately.
Injectable options such as the GLP-1 agonists liraglutide and semaglutide have seen promising weight-loss results, however at the time of writing supply is limited and people with existing T2DM are being prioritised for its use.
For those with a BMI ≥ 40 kg/m2, or 35–39.9 kg/m2 with significant weight-related comorbidities, referral for bariatric surgery can be considered (a lower BMI threshold applies to those from certain ethnic minority groups as shown in Table 1) (NICE, 2014).
Polycystic ovary syndrome
PCOS is thought to affect approximately 10% of women in the UK. It is associated with high androgen levels, obesity, dysfunctional ovulatory cycles, cystic ovaries, and insulin resistance (Zhao et al., 2023). Women with PCOS have a higher risk of developing GDM.
Current primary care guidance suggests that all women with PCOS who are considering pregnancy should be offered an oral glucose tolerance test (OGTT) prior to conception, and before 20 weeks’ gestation in those who are already pregnant. NICE recommends that all women with PCOS are offered screening for GDM using the OGTT between 24 and 28 weeks’ pregnancy (NICE, 2023). Hormonal therapies that people with PCOS may be taking (such as medroxyprogesterone or the combined oral contraceptive pill) to regulate bleeding should be stopped.
Ethnicity
Some ethnic groups, for example those from South Asian, Black and Middle Eastern backgrounds are at a higher risk of developing GDM. Diabetes UK provides an excellent compendium of accessible information for patients with GDM in different languages, including dietary advice for different food traditions. It is important that these patients are followed up appropriately. These patients and their children often experience significant health inequalities and are disproportionately affected by the long-term sequelae of GDM (Robertson et al., 2021).
Genetics
Evidence suggests that GDM may represent early manifestation of T2DM, sharing similar genetic variants, and provoked in susceptible individuals by the physiological insulin resistance of pregnancy. Although some individuals are genetically predisposed to GDM, primary care can focus on the modifiable risk factors, ideally in the pre-conception period, to maximise the health of mother and baby.
Role of primary care
Clinicians can opportunistically discuss conception plans, GDM risk, family history, and modifiable risk factors with women of childbearing age. GPs are well placed to provide advice and support about healthy diet and physical activity. Some GPs may work at the public health level on improving environmental factors that shape health behaviours, for example, green space, affordable healthy food, social prescribing, and active travel.
For people post-partum, clinicians must ask specifically about GDM and ensure that it is coded correctly in the notes, organise a fasting blood glucose test within 12 weeks of delivery, and diarise annual HbA1c monitoring. Women should also be offered a referral to the NHS Diabetes Prevention Programme, an evidence-based programme that aims to modify lifestyle factors and has been proven to reduce the risk of progression to T2DM (NHS England, n.d.). At the time of writing it is accessible via face-to-face groups or digitally.
NICE guidelines
The most recent NICE guidelines were updated in 2020 (NICE, 2020). The following risk factors need to be assessed at booking:
BMI ≥ 30 kg/m2 Previous macrosomic baby ≥4.5 kg Previous GDM First-degree relative with diabetes A high-risk ethnic group (South Asian, Black Caribbean and Middle Eastern women)
This is usually completed by the midwife at the booking appointment; women with any of these risk factors should be offered an OGTT to screen for GDM between 24 and 28 weeks of pregnancy. In addition, an OGTT should be offered to women who are found at routine antenatal appointments to have 1+ glycosuria on two occasions or 2+ glycosuria on one occasion.
Women with a previous history of gestational diabetes should be offered early glucose self-monitoring, an OGTT at booking, and a further OGTT at 24–28 weeks of pregnancy if the first OGTT results are normal (NICE, 2020). It may be that women seek prescriptions for glucose testing strips from primary care and these should be actioned in a timely manner to aid optimal blood sugar control.
GDM is diagnosed if a woman has a fasting plasma glucose level of ≥5.6 mmol/L or a 2-hour plasma glucose level of ≥7.8 mmol/L (NICE, 2020). Any woman with a diagnosis of GDM should be offered a review from the joint diabetic antenatal clinic within 1 week, and their primary care team be notified (NICE, 2020). Those with GDM will be under the care of a specialist obstetric team and usually be encouraged to give birth in hospital with a consultant-led maternity and neonatal unit.
Further interventions include an explanation of the implications of GDM, the importance of good blood sugar control, dietary and physical activity guidance, the importance of low glycaemic index foods, and specialist assessment of the need for blood-glucose-lowering agents such as metformin and/or insulin. If a woman has a fasting blood glucose level that is less than 7 mmol/L, then a trial of diet and exercise may be trialled for 1–2 weeks. If this is not successful, metformin is offered, with insulin added if glucose targets are still not met.
Most antenatal clinics have now adopted remote monitoring of blood sugars, reducing the burden of appointments, and streamlining diabetic advice and control via text or phone call. Nevertheless, the amount of information patients receive at antenatal appointments can be overwhelming, and it is thus important to ensure that the implications of GDM are highlighted opportunistically when patients present to primary care during their pregnancy.
Following delivery any anti-diabetic agents are stopped and blood glucose is checked in hospital to ensure that it is normal. A repeat fasting blood glucose should be offered to all women by their GP between 6 and 13 weeks following delivery and acted upon appropriately (Table 2) (NICE, 2020). If the blood test is arranged after 13 weeks post-partum, an HbA1c test can be used as the investigating tool.
A quick reference guide giving an overview of primary care actions to be taken depending on post-partum fasting blood glucose test result.
Although NICE guidance suggests that women with a post-partum HbA1c of ≥48 mmol/mol can be diagnosed with T2DM, a confirmatory test may be sensible depending on the proximity of delivery to blood test as HbA1c reflects an average blood sugar over 3 months. Source: NICE, 2020; Platts and Agarwal, 2015.
All women should be offered help to achieve a healthy weight, general advice regarding healthy diet and physical activity, and should be considered for referral to the NHS Diabetes Prevention Programme (NHS England). Finally, it is of utmost importance that women with GDM are recalled for annual T2DM screening using HbA1c or fasting glucose in primary care (Platts and Agarwal, 2015).
Key points
Ensure that you communicate openly, honestly, and thoroughly with patients about the perinatal and long-term risks of GDM and seek ways to work together to reduce their risk factors Engage opportunistically with patients of childbearing age to consider all aspects of pre-conception advice Patients who may be at higher risk of developing GDM should seek to minimise their modifiable risks pre-conception Educate your patients about their personal risk of GDM and signpost appropriately to resources such as www.diabetes.org.uk for further support Correct coding and regular audit of patients with GDM in primary care is important to ensure appropriate recall for annual diabetic screens Ensure that patients with GDM are offered adequate information post-partum to reduce their long-term risks of developing diabetes and offer referral to the NHS Diabetes Prevention Programme
