Gestational diabetes mellitus is defined as diabetes with first onset or recognition during pregnancy (Skajaa et al, 2020). It is typically identified during the second or third trimester of pregnancy, representing insufficient insulin production or increased insulin resistance secondary to placental hormone release, with resolution following birth (Skajaa et al, 2020).
A 60% reduction in insulin sensitivity is seen in all pregnancies (Catalano, 2014), typically after approximately 20 weeks' gestation (Kampmann et al, 2019). Reduced peripheral insulin sensitivity causes reduced insulin-stimulated glucose uptake in skeletal muscle. In combination with reduced hepatic suppression of glucose production in response to insulin and an inability of pancreatic beta cells to meet the increased insulin demands during pregnancy, gestational diabetes mellitus is clinically apparent in the development of hyperglycaemia (Catalano, 2014). In line with the timing of these hormonal changes, screening for gestational diabetes mellitus occurs at 24–28 weeks, although this can occur earlier in women considered at increased risk (Diabetes UK, 2023).
Prevalence
Gestational diabetes mellitus is the most common medical condition to affect pregnant women, reported to affect 10–20% of pregnancies in England (NHS England, 2024a). Its prevalence is increasing because of an increasing at-risk population. Worldwide, adult obesity has more than doubled since 1990, with 43% of adults over 18 years old being overweight and 16% being obese in 2022 (World Health Organization, 2024). This preventable disease affects young people as well, with over 390 million children and adolescents (age 5–19 years) being overweight, including 160 million living with obesity in 2022 (World Health Organization, 2024), with repercussions for pregnancy health.
In the USA, gestational diabetes mellitus is reported in 2–10% of pregnancies (Quintanilla Rodriguez and Mahdy, 2024), but reporting depends on screening and diagnosis. Discrepancies in the availability and access to screening make available figures potentially unreliable. In the UK, the national gestational diabetes mellitus audit has been funded for 3 years as part of the National Gestational Diabetes Mellitus Audit programme, beginning in 2022/23 (NHS England, 2024a). It aims to develop greater understanding of how many women are diagnosed with gestational diabetes mellitus throughout the NHS, and whether health inequalities are being addressed. This will review the diagnosis of gestational diabetes mellitus, ethnicity, deprivation quintile, parity, body mass index and smoking history (NHS England, 2024a).
Causes
Gestational diabetes mellitus is caused by one or both of insulin resistance or insufficient insulin secretion (Powe et al, 2016). Pregnancy is a dynamic time for insulin secretion and increases in insulin production in early pregnancy have been identified (Powe et al, 2019). Pregnancy hormones, such as human placental lactogen and prolactin, can directly increase insulin production. Genetic data suggest that pancreatic beta cell function is an important factor in the risk of developing gestational diabetes mellitus. Women with gestational diabetes mellitus may have less beta cell capacity to increase insulin secretion.
Insulin resistance is an important pathophysiological mechanism in gestational diabetes mellitus. Many women have some insulin resistance prior to pregnancy, exacerbated by metabolic changes in pregnancy. Placental growth factor increases systemic insulin resistance. Clinical features that suggest insulin resistance include acanthosis nigricans or polycystic ovarian syndrome. Biochemical parameters may help to identify increased risk, including reduced high density lipoproteincholesterol levels, raised triglyceride levels and haemoglobin A1c (HbA1c) above 5.7% (39 mmol/mol) (Quintanilla Rodriguez and Mahdy, 2024).
Screening and diagnosis
Universal vs selective or targeted screening
Globally, guidelines for the screening and diagnosis of gestational diabetes mellitus lack consensus. Universal screening of all pregnant women, although ideal in areas where prevalence is high, is resource intensive. Alternatively, targeted or selective screening focusing on risk factors may miss up to 20% of women with no risk factors at booking or those with inadequate history (Chevalier et al, 2011; Avalos et al, 2013; Meek, 2017). Women may have more than one risk factor (Solomon et al, 1997; American College of Obstetricians and Gynecologists, 2018).
The USA conducts universal screening of all pregnant women (Moyer and U.S. Preventive Services Task Force, 2014), whereas the UK targets high-risk individuals (National Institute for Health and Care Excellence (NICE), 2015). Risk factors assessed in the UK include obstetric history of previous gestational diabetes mellitus or macrosomic baby (birth weight >4.5kg), first degree relative diabetes history, pre-pregnancy body mass index >30kg/m2 and women from minority ethnic groups with high diabetes prevalence. Additional risk factors considered outside of the UK include maternal age >35 years, biochemical indictors of glucose intolerance and polycistic ovarian syndrome (ElSayed et al, 2023).
Screening timing
In the UK, NICE (2015) guidelines recommend screening at-risk women at 24–28 weeks using a 2-hour 75g oral glucose tolerance test. For those with gestational diabetes mellitus history, NICE (2015) recommends early self-monitoring of blood glucose or a 2-hour 75g oral glucose tolerance test, ideally soon after booking, with a repeat oral glucose tolerance test at 24–28 weeks if initial tests are normal. Evidence suggests that early screening and treatment of gestational diabetes mellitus in women at elevated risk of hyperglycaemia reduces adverse neonatal outcomes but not maternal outcomes, with the potential risk of overtreatment of mild gestational diabetes mellitus identified before 20 weeks (Simmons et al, 2023).
Choice of test
While widely used, the oral glucose tolerance test is not a perfect test. Detailed patient preparation is crucial for accurate results. Prompt referral to specialised antenatal and diabetes clinic should follow diagnosis. In the UK, the one-step 2-hour 75g oral glucose tolerance test follows either the NICE (2015) criteria or the International Association of the Diabetes and Pregnancy Study Groups thresholds (Metzger et al, 2010). Only one abnormal value is necessary to make a diagnosis.
Other testing strategies
Table 1 provides a comparison of the criteria used to diagnose gestational diabetes mellitus across various guidelines. In the USA, testing methods vary. The American Diabetes Association (2014) follows the World Health Organization (2013) and International Association of the Diabetes and Pregnancy Study Groups (Metzger et al, 2010) criteria, while the American College of Obstetricians and Gynecologists (2018) endorse the Carpenter-Coustan (1982) or National Diabetes Data Group (1979) thresholds. This is a two-step approach: initially women have an O'Sullivan random 1-hour 50g glucose challenge test with abnormal result proceeding to a 3-hour 100g oral glucose tolerance test (American Diabetes Association Professional Practice Committee, 2024). Two abnormal values are needed to make a diagnosis, which has implications for the population diagnosed. The reliance on the 50g glucose tolerance test and two abnormalities on an oral glucose tolerance test might miss women with marked fasting hyperglycaemia.
| Criteria | International Association of the Diabetes and Pregnancy Study Groups (Metzger et al, 2010); American Diabetes Association (2014); World Health Organization (2013) | National Institute for Health and Care Excellence (2015) | American College of Obstetricians and Gynecologists (2018) | |
|---|---|---|---|---|
| Carpenter-Coustan (1982) | National Diabetes Data Group (1979) | |||
| Who should be screened | Background population frequency of dysglycaemia/local practice | Selective | Universal | Universal |
| Timing of testing | 24–28 weeks | Screen early if previous gestational diabetes mellitus 24–28 weeks | Screen early if high risk of hyperglycaemia or previous gestational diabetes mellitus 24–28 weeks | Screen early if high risk of hyperglycaemia or previous gestational diabetes mellitus 24–28 weeks |
| Oral glucose tolerance test (g) | 75 | 75 | 100 | 100 |
| Number of steps | 1 | 1 | 2 |
2 |
| Number of abnormalities | ≥1 | ≥1 | ≥2 | ≥2 |
| Fasting plasma glucose (mmol/l) | 5.1 | 5.6 | 5.3 | 5.8 |
| 1-hour oral glucose tolerance test | 10 | - | 10 | 10.6 |
| 2-hour oral glucose tolerance test | 8.5 | 7.8 | 8.6 | 9.2 |
| 3-hour oral glucose tolerance test | - | - | 7.8 | 8 |
Some centres test HbA1c at booking for all pregnant women to identify those with pre-existing diabetes, defined as HbA1c >6.5% or 48mmol/mol (Cowie et al, 2010), for immediate management. Glycosuria of ≥1 on two occasions or 2+ on one occasion should prompt further testing.
Management
Glucose targets
The NICE (2015) and American Diabetes Association (ElSayed et al, 2023) guidance for glucose targets in gestational diabetes mellitus are outlined in Table 2. Diet and lifestyle are considered essential to management, allowing many women to meet their glucose targets without medication (NICE, 2015; Dolatkhah et al, 2018; Yamamoto et al, 2018; Kapur et al, 2020; ElSayed et al, 2023). NICE (2015) recommends a trial of dietary and exercise modifications in uncomplicated gestational diabetes mellitus (no macrosomia or hydramnios) where fasting plasma glucose is <7mmol/L at diagnosis.
| Guidance | Blood glucose (mmol/l) | ||
|---|---|---|---|
| Fasting | 1-hour post-meal | 2-hour post-meal | |
| National Institute for Health and Care Excellence (2015) | <5.3 | <7.8 | <6.4 |
| American Diabetes Association (2014) | <5.3 | <7.8 | <6.7 |
Diet
It is recommended that registered dietitians, who are knowledgeable about the subject, provide dietary education and individualised advice with regular follow up (NICE, 2015; ElSayed et al, 2023). The aims of a diet plan are to promote a balanced diet that ensures attainment of glucose targets, promotes maternal and fetal health and avoids excessive gestational weight gain (NICE, 2015; Dolatkhah et al, 2018; ElSayed et al, 2023). There is no evidence to support specific calorie or macronutrient intake for people with gestational diabetes mellitus. The Institute of Medicine (IOM) and National Research Council (NRC) (2009) make the following recommendations for all pregnant women: at least 175g of carbohydrate, 71g of protein and 28g of fibre per day.
Carbohydrates
Previously focus was on carbohydrate restriction, as it is the main food group that directly affects glucose levels (Jovanovic-Peterson and Peterson, 1990). However, this generally accepted approach was challenged on the basis that glucose is the main energy source for the placenta and fetus (Hernandez and Brand-Miller, 2018), and the IOM and NRC (2009) recommend 46–65% energy comes from carbohydrates to ensure adequate fetal growth and cerebral development. Some women restrict carbohydrate intake excessively to achieve glucose targets. Education against this is important, as there is concern about the risks of ketone formation causing harm to the baby. Fasting urine ketone testing can be useful to identify this (ElSayed et al, 2023). Excessively restricting carbohydrates also risks their substitution with unhealthy fats, which adversely affects fetal body composition and increases maternal insulin resistance.
Studies show that post-prandial and fasting glucose targets can be achieved with increased intake of higher quality carbohydrates (Hernandez et al, 2014; 2018). Furthermore, there is evidence that a lower glycaemic index diet, higher in fibre, reduces the risk of macrosomia and insulin requirement (Wei et al, 2016). Spreading carbohydrates over three small-to-moderate meals and 2–4 snacks can support adequate carbohydrate intake while meeting glucose targets (Mcintyre et al, 2019; Rasmussen et al, 2020). Simple carbohydrates cause higher post-prandial glucose levels; therefore, added sugar in drinks or food should be avoided (ElSayed et al, 2023). Artificial sweeteners are a good substitute to help achieve glucose targets. However, research suggests that artificially sweetened beverages can increase a child's risk of being overweight/obese in later life. Glucose targets are achievable without their use (Zhu et al, 2017).
Exercise
Aerobic and/or resistance exercise at moderate intensity lasting 20–50 minutes a minimum of twice a week has been shown to help achieve glucose targets and reduce initiation and insulin requirements (Laredo-Aguilera et al, 2020). Alternatively, walking after meals for at least 10–15 minutes can also have beneficial effects on postprandial glucose levels (NICE, 2015; Lende and Rijhsinghani, 2020).
Gestational weight gain
Controlling weight gain after a gestational diabetes mellitus diagnosis is important, as weight gain later in pregnancy has been associated with large for gestational age babies, greater risk of instrumental birth, increased daily insulin requirement and a higher result in a postpartum 2-hour oral glucose tolerance test (Aiken et al, 2019). The IOM and NRC (2009) recommended weight targets for pregnant women, but these are not specific to gestational diabetes mellitus.
Observational data suggest that in overweight and obese women, modest weight loss in the third trimester may be beneficial, with improved maternal and fetal outcomes (Yee et al, 2013). The DiGest study is currently being carried out, and aims to identify the effects of a reduced energy diet in women with gestational diabetes mellitus from 28 weeks on maternal weight gain and fetal birth weight, among other outcomes (Kusinski et al, 2020). Results are expected in late 2024. After birth, advice on weight management, diet and exercise should be given to all women with gestational diabetes mellitus to support diabetes prevention (NICE, 2015).
Pharmacologic treatment
Metformin
Metformin is recommended for gestational diabetes mellitus if glucose levels remain above target fasting and post-prandial levels after 1–2 weeks, despite diet and exercise (NICE, 2015). Several meta-analyses confirm its safety and non-teratogenicity throughout pregnancy, including during the first trimester (Farrar et al, 2017; Barbour and Feig, 2019). In the EMERGE trial, early metformin use led to less gestational weight gain with lower infant birth weights (Dunne et al, 2023). Other studies have shown consistent results, with less gestational weight gain, fewer instances of pre-eclampsia, lower rates of large for gestational age or macrosomic infants (birth weight >4000g) in metformin users than those on insulin or glibenclamide, with reduced neonatal hypoglycaemia (Farrar et al, 2017). However, metformin can cross the placenta, raising concerns about the long-term metabolic effects on offspring (van Weelden et al, 2018).
Insulin
If pregnancy blood glucose targets cannot be met despite dietary and activity changes and metformin, insulin should be offered (NICE, 2015). For women diagnosed with gestational diabetes mellitus and fasting plasma glucose ≥7.0 mmol/L, immediate treatment with insulin, with or without metformin, and lifestyle changes should be offered. If fasting plasma glucose is between 6.0 and 6.9mmol/l with complications such as macrosomia or hydramnios, immediate treatment with insulin, along with metformin, dietary and exercise changes should be considered.
Insulin therapy is required in 15–30% of gestational diabetes mellitus pregnancies to maintain target blood glucose levels (Eleftheriades et al, 2021). NICE (2015) guidelines recommend the use of isophane insulin as the first-line intermediate acting insulin of choice. Rapid-acting analogue insulin (aspart or lispro) is preferred for post-prandial hyperglycaemia management in pregnancy. A personalised insulin plan should aim to achieve target glucose levels without hypoglycaemia. Insulin may be prescribed as bolus only, basal only or a basal-bolus regimen based on glucose patterns. Women may temporarily require increased insulin doses if steroids are necessary for fetal lung maturation (NICE, 2015). Women treated with insulin should be educated about hypoglycaemia risks, aiming to maintain glucose levels above 4mmol/l. They should always have fast-acting glucose available, such as jelly babies, dextrose tablets or glucose drinks.
Glucose monitoring
Women with gestational diabetes mellitus on multiple daily insulin injections are advised to self-monitor their fasting, pre-meal, 1-hour post-meal and bedtime capillary blood glucose levels. All others should monitor their fasting and 1-hour post-meal blood glucose levels. Although there is no national consensus on this, continuous glucose monitoring is increasingly being used in women with insulin-treated gestational diabetes mellitus and is particularly useful if there is problematic hypoglycaemia or if blood glucose levels remain unstable despite maximum efforts (NICE, 2015). Insulin-treated women with gestational diabetes mellitus should follow Driver and Vehicle Licensing Agency rules while driving (Gov.uk, 2024).
Intrapartum, birth and postnatal monitoring
Antenatal fetal monitoring
Women with diabetes should be offered fetal growth scans every 4 weeks from 28–36 weeks' gestation to monitor growth and amniotic fluid volume (NICE, 2015). This measurement is plotted on a centile growth chart.
Birth planning
NICE (2015) guidance recommends that women with gestational diabetes mellitus give birth no later than 40+6 weeks' gestation in a hospital equipped with neonatal facilities. If birth has not occurred by this stage, induction of labour or elective caesarean section is recommended. For those who have complications, such as polyhydramnios, growth concerns or uncontrolled hyperglycaemia, birth should be considered earlier. An intrapartum birth plan for diabetes management should be agreed and documented in the medical notes.
Labour and birth
NICE (2015) recommends hourly glucose monitoring during labour, with glucose levels ideally between 4 and 7mmol/l. Following the birth of the baby and placenta, all hypoglycaemic agents (usually metformin and insulin) should be stopped. Glucose monitoring is advised for 24 hours post-birth to exclude pre-existing diabetes (NICE, 2015; Joint British Diabetes Societies, 2023) or as per local trust policy.
Infant feeding
Healthy term babies of women with gestational diabetes mellitus should be fed within 30–60 minutes of birth. Blood glucose levels should be tested within 2–4 hours of birth and before their second feed (NICE, 2015; Levene and Wilkinson, 2019). There is international controversy regarding the optimal threshold for diagnosing neonatal hypoglycaemia, with thresholds ranging from 2.0–2.6mmol/l (van Kempen et al, 2020). The British Association of Perinatal Medicine recommends treating hypoglycaemia in a baby with a glucose of less than 2mmol/l (with no abnormal clinical signs) on two occasions or any instance less than 2.5mmol/l in the presence of abnormal clinical signs in term infants (>37 weeks' gestation) (Levene and Wilkinson, 2019). Babies born to women with gestational diabetes mellitus should have two consecutive glucose readings >2.0mmol/l and should only be discharged to community after 24 hours (NICE, 2015; Levene and Wilkinson, 2019). Breastfeeding is highly beneficial for both its immediate and long-term health outcomes for both mother and baby and should be actively encouraged and supported.
Short-term follow up after birth
Three months after birth, a HbA1c or fasting plasma glucose test should be performed to ensure diabetes resolution (NICE, 2015). HbA1c testing should be repeated annually as women with gestational diabetes mellitus are seven times more likely to develop type 2 diabetes mellitus (Bellamy et al, 2009). Up to 50% of women with gestational diabetes mellitus may develop type 2 diabetes mellitus within 5 years(Bengtson et al, 2021). Lifestyle advice should be provided to these women. If their fasting plasma glucose level ≥7mmol/l, confirmatory testing for type 2 diabetes mellitus is needed. If HbA1c is ≥6.5%(48mmol/mol), care should be provided for type 2 diabetes mellitus, normally in primary care (NICE, 2015). All women with a history of gestational diabetes mellitus should be referred to the NHS Diabetes Prevention Programme (NICE, 2015; NHS England, 2024b).
Future pregnancy planning
Inform women that gestational diabetes mellitus may recur in future pregnancies and that glucose levels should be in range prior to embarking on another pregnancy. In subsequent pregnancies, prompt referral for early screening with oral glucose tolerance test or with self-monitoring of blood glucose is advisable. Offer contraception advice.
Long-term risks and follow up
Risks to the mother
Gestational diabetes mellitus is associated with a higher risk of cardiometabolic complications; the rising obesity pandemic and increasing maternal age plays a role in this (Daly et al, 2018; Saravanan et al, 2020; Sweeting et al, 2022). Women with gestational diabetes mellitus have a higher likelihood of developing type 2 diabetes mellitus, almost 7–10 fold compared to women who did not have gestational diabetes mellitus (Bellamy et al, 2009; Vounzoulaki et al, 2020). They also have a higher likelihood of developing ischaemic heart disease (three-fold), hypertension (two-fold), hyperlipidaemia and obesity (Daly et al, 2018; Kramer et al, 2019; Saravanan et al, 2020).
Even without developing type 2 diabetes mellitus, women with previous gestational diabetes mellitus are still at a two-fold risk of cardiovascular events in the future (Kramer et al, 2019; Sweeting et al, 2022). These complications emerge earlier and persist for up to 25 years (Daly et al, 2018). Early onset type 2 diabetes mellitus (≤40 years) is increasing globally, with obesity driving the incidence (Misra et al, 2023). Although there is a paucity of research in this cohort, they are reported to have higher risks of complications that are more aggressive in nature (Sargeant et al, 2020; Misra et al, 2022). Moreover, pregnancy among these childbearing age women are at high risk of adverse outcomes (Meek, 2022; Misra et al, 2023). Preconception planning (Marcus et al, 2022) and referral to the NHS Diabetes Prevention Programme post-birth is imperative.
Risks to offspring
Offspring of women with gestational diabetes mellitus inherit long-term metabolic risks. Children have a higher risk of abnormal glucose metabolism, increased insulin resistance and elevated risks of being overweight/obese and having cardiovascular outcomes, with events occurring earlier in life (Sweeting et al, 2022). The cardiometabolic risks of offspring are directly related to maternal glycaemic control during pregnancy, possibly mediated through fetal hyperinsulinism and abnormal lipid metabolism (Szmuilowicz et al, 2019; Meek, 2023). The Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study group carried out research involving women and their children 10–14 years postpartum; they demonstrated that 52.2% of women with gestational diabetes mellitus history developed a disorder of glucose metabolism, compared with 20.1% of women without gestational diabetes mellitus history, along with increased percentages of children with obesity, body fat percentage, waist circumference and sum of skin folds (Lowe et al, 2018). Lactation appears to confer protection against the development of cardiometabolic complications, aiding with weight loss and improving glucose homeostasis postpartum and beyond, with longer durations offering greater protection (Gunderson et al, 2015; Vandyousefi et al, 2019; Thayer et al, 2020; Moon and Jang, 2022).
Follow up
To mitigate the risks, a holistic approach focusing on preventive measures and metabolic risk management is recommended. Regular screening protocols and timely management of modifiable cardiovascular risk factors (obesity, diabetes, hypertension, hyperlipidaemia) are essential. The American Heart Association and American College of Obstetricians and Gynecologists state that ‘all well-woman visits, including the postpartum follow-up visit, should be considered an opportunity to focus on lifestyle choices that optimize cardiac health, including weight management, smoking cessation, physical activity assessment, nutritional counselling, and stress reduction. This is especially important for those with pregnancy complications that suggest an increased risk for premature cardiovascular events’ (Brown et al, 2018). Compliance to this remains poor, underscoring the need for ongoing awareness emphasising participation in screening and institution of early interventions (NICE, 2015; Sweeting et al, 2022). Long-term support structures for women and offspring post-gestational diabetes mellitus are essential for better health outcomes (Dennison et al, 2022).
Conclusions
Gestational diabetes, the leading medical disorder complicating pregnancy, is managed through diet, exercise and pharmacotherapy and typically resolves postpartum. The lack of global screening and diagnostic standards presents a golden opportunity for researchers in this field. Novel biomarkers and risk scores may help stratify women with early gestational diabetes mellitus and provide them with tailored treatment options. Precision medicine holds promise in unravelling pathophysiological mechanisms to provide personalised care.
Gestational diabetes mellitus should not be viewed as a condition that complicates pregnancy only transiently, but as a condition with lasting implications for both maternal and offspring health. This comprehensive approach not only addresses glucose targets during pregnancy but also considers the long-term cardiometabolic consequences on the health of future generations in managing gestational diabetes mellitus.