Key learning points:
– How gestational diabetes is diagnosed and treated
– What can be done to prevent further increases in the prevalence of the condition
Gestational diabetes (GDM) is defined as carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy.1 GDM defined in this way includes women with undiagnosed pre-existing diabetes, as well as women with first onset during pregnancy. In the past, less severe GDM was referred to as impaired glucose tolerance, and more severe cases as GDM. Now the whole higher end of the glucose spectrum is referred to as GDM.
GDM is the most common metabolic disorder of pregnancy with rates varying between 1 and 24% depending on population characteristics (for example, Asian or black ethnicity) and diagnostic criteria (glucose thresholds).2 GDM prevalence is increasing alongside the prevalence of maternal obesity and physical inactivity.
The National Institute for Health and Care Excellence (NICE) recommends that women who have had GDM in a previous pregnancy should be offered diagnostic testing as early as possible after pregnancy booking (in the first or second trimester). NICE also recommends that the risk of GDM is assessed at first pregnancy booking in any non-diabetic woman using maternal characteristics or risk factors. Diagnostic testing should be offered at 26 to 28 weeks if a woman has one or more of these risk factors:
– Family history of diabetes.
– Ethnicity with a high prevalence of diabetes (South Asian, black or Middle Eastern).
– Previous history of having a macrosomic baby (usually defined as birthweight >4kg).
– Body mass index (BMI) ≥30 kg/m2.
– Previous GDM.3
However, these risk factors are not totally reliable, and to ensure women with GDM are not missed, most may need to be tested.4
The International Association of Diabetes in Pregnancy Study Groups5 (IADPSG), endorsed by the World Health Organization (WHO),6 goes further. It recommends that all women not previously identified as having type 2 diabetes are offered a diagnostic test, regardless of risk factors.
NICE’s approach of offering testing to only women with a risk factor may miss some women with hyperglycaemia who may benefit from treatment. The IADPSG approach may unnecessarily test women at low risk, but will identify more women and therefore more will benefit from treatment. It is unclear which screening and testing approach is most clinically beneficial or cost-effective.4,7,8
The oral glucose tolerance test (OGTT) is generally used to diagnose GDM and is usually administered between 26 to 28 weeks gestation. A plasma blood sample is obtained after an overnight fast. Then a 75g or 100g glucose load is given and further plasma blood sample obtained after one, two or three hours. GDM is diagnosed (depending on the criteria used) if one, two or more glucose levels are exceeded.
Other tests to diagnose GDM have been evaluated including jelly beans, chocolate bars and meals, however studies are few and include small numbers of women. Consequently there is no clear evidence to suggest which test is superior.
GDM is associated with an increased risk of adverse perinatal outcomes including:
– Large for gestational age (LGA).
– Induction of labour and caesarean section.9
There is also growing evidence that GDM is associated with increased risk of longer-term ill-health outcomes in the mother (eg type 2 diabetes and cardiovascular disease)10,11 and in the offspring (eg obesity and associated cardio-metabolic risk).12,13
Recent studies2,14 show graded linear associations between glucose levels and adverse outcomes, including caesarean section, large for gestational age and infant adiposity,2,14 which means there is no clear clinical threshold where risk increases significantly, and no threshold to diagnose GDM and offer treatment. So how do we identify glucose thresholds to diagnose GDM?
First, we have to decide what we are hoping to achieve from diagnosis. Previously the aim was to identify women at risk of future type 2 diabetes.15 More recently, the aim was to reduce the risk of perinatal adverse outcomes and we know from treatment trials that controlling and reducing hyperglycaemia reduces the risk of these outcomes16,17 and this is important to both women and clinicians.18 Importantly, there is now evidence that the offspring of women who have had GDM are at increased risk of future obesity and cardiometabolic ill-health. Reducing these longer-term risks is key for the future health of the population, though there is no evidence from randomised trials to suggest treatment reduces the risk of these outcomes, because no longer-term follow-up has been conducted.
So the aim of identifying and treating GDM is to reduce the risk of longer-term ill-health in the offspring of women who have had GDM. In spite of the absence of evidence, IADPSG chose the following perinatal outcomes to determine new thresholds because of their association with later life obesity and cardiometabolic risk:
– Large for gestational age (LGA).
– High adiposity at birth.
– High cord c-peptide levels.12
The IADPSG5 derived its new threshold criteria using data from the HAPO study (which showed graded linear associations between glucose and LGA, high adiposity and high cord c-peptide levels).14 Because there are no clear clinical thresholds, the IADPSG derived glucose values to capture most infants at risk of the above, these glucose levels are therefore somewhat arbitrary.
The IADPSG recommended thresholds are plasma glucose levels of:
– 5.1 mmol/l for fasting.
– 10.8 mmol/l one hour post-load after 75g oral glucose tolerance test (OGTT).
– 8.5 mmol/l two hour post-load.
These thresholds have been recently endorsed by the WHO.6
NICE, however, recommends different thresholds:
– 5.6mmol/l for fasting.
– 7.8mmol/l two-hour post-load after 75g OGTT.
NICE is not clear how these figures were derived.3,19 Given the linear association between glucose levels and risk of adverse outcomes, it is likely that identifying and treating women at lower glucose levels will result in a reduction in risk. However, the effectiveness of either of these recommended criteria is unknown, prompting calls for trials investigating the application of different thresholds on maternal and offspring health outcomes.
Once GDM is diagnosed, treatment can be offered. Women should be cared for by a team of clinicians including: midwife, obstetrician, diabetologist, dietician and diabetic nurse specialist. Care should be individualised according to:
– The woman’s views and needs.
– The degree of hyperglycaemia, glucose control and presence/absence of abnormalities (for example medical conditions such as hypertension or a fetus that is large for gestational age).
This approach allows variation in the intensity of treatment. For example, women with less severe hyperglycaemia, whose glucose levels are well controlled with diet modification, may require less intensive monitoring and input than women who have more severe hyperglycaemia needing a pharmacological intervention to control glucose levels. Evidence suggests a step-up approach is effective; this is where diet and lifestyle modification are used as first line, with pharmacological interventions (metformin, glibenclamide and/or insulin) if these are partly or wholly unsuccessful.4,20,21
Oral hypoglycaemic agents (metformin and glibenclamide [glyburide]) present a possible alternative to injected insulin and are effective as first-line pharmacological intervention, and are perhaps more acceptable to women.
The step-up approach ensures that interventions are only offered if required, resulting in less burden for the woman and the NHS, which is particularly important given the increasing prevalence of GDM. NICE now recommends women with GDM are advised to eat a ‘healthy diet’ during pregnancy, and emphasises that foods with a low glycaemic index should replace those with a high glycaemic index and that women should walk 30 minutes a day to improve glucose control, though there is no evidence of the effectiveness of this advice.
As with care during pregnancy, care during labour should be individually tailored. Women with well controlled or less severe hyperglycaemia, with a normally grown fetus may need less intensive monitoring or intervention such as induction, compared with a woman who has less well-controlled hyperglycaemia with a fetus that is large for gestational age.
Care following birth
For most women, insulin resistance rapidly returns to normal following birth. Therefore glucose-lowering treatments should be stopped if blood glucose levels decline and stay within normal parameters. Care of women following normalisation of glucose levels is therefore the same as for any woman, though care should be individualised.
The care of infants of women who have had GDM depends on the infant’s health and adaptation at birth. These infants are at increased risk of hypoglycaemia, so early, sustained and adequate feeding is essential. All infants should be monitored for wellbeing and signs of hypoglycaemia, particularly in the first 24 hours. Any infant who is asymptomatic should be allowed to demand feed and should not be subjected to invasive glucose level monitoring. Infants who show hypoglycaemia or poor adaptation may need supplemental feeds and closer monitoring, including glucose estimation.
Women who have had GDM have an increased risk of developing type 2 diabetes10 and should fully understand this and the signs and symptoms. Postnatal blood glucose testing should be offered six to 12 weeks following birth and yearly thereafter, to identify continuing insulin resistance and hyperglycaemia. NICE recommends fasting plasma assessment3 though the test that adequately identifies continuing postnatal insulin resistance may depend on population characteristics. It may be that the full glucose tolerance test is more appropriate in some populations.22,23
It is important to understand that the risk of adverse outcomes increases with rising glucose level (measured by the OGTT in pregnancy), across the whole glucose spectrum. To target treatments at women most likely to benefit, a diagnosis of GDM needs to be made. However, all women can benefit from adopting a healthier lifestyle.
1. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039-57.
2. Farrar D, Fairley L, Santorelli G et al. Association between hyperglycaemia and adverse perinatal outcomes in south Asian and white British women: analysis of data from the Born in Bradford cohort. The Lancet Diabetes & Endocrinology 2015;3:795-804.
3. NICE. Diabetes in pregnancy: management from preconception to the postnatal period. NG3, 2015.
4. Farrar D, Simmonds M, Griffin S et al. The identification and treatment of women with hyperglycaemia in pregnancy: an analysis of individual participant data, systematic reviews, meta-analyses, and an economic evaluation HTA. In press.
5. International Association of Diabetes and Pregnancy Study Groups Consensus panel. International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy. Diabetes Care 2010;33:676-82.
6. World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy. WHO, 2013.
7. Farrar D, Lawlor D, Duley L. Different testing strategies for diagnosing gestational diabetes mellitus to improve maternal and infant health. Cochrane Database of Systematic Reviews, 2011.
8. Tieu J, Middleton P, McPhee A, Crowther C. Screening and subsequent management for gestational diabetes for improving maternal and infant health. Cochrane Database of Systematic Reviews, 2010.
9. Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Annals of Internal Medicine 2013;159:123-9.
10. Bellamy L, Casas J-P, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009;373:1773-79.
11. Shah BR, Retnakaran R, Booth GL. Increased Risk of Cardiovascular Disease in Young Women Following Gestational Diabetes Mellitus. Diabetes Care 2008;31:1668-9.
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13. Lawlor DA, Fraser A, Lindsay RS, et al. Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort. Diabetologia 2010;53:89-97.
14. HAPO Hyperglycemia and Adverse Pregnancy Outcomes. The New England Journal of Medicine 2008;358:1991-2002.
15. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. American Journal of Obstetrics & Gynecology 1982;144:768-73.
16. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. The New England Journal of Medicine 2005;352:2477-86.
17. Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. The New England Journal of Medicine 2009;361:1339-48.
18. Bain E, Middleton P, Crowther CA. Progressing towards standard outcomes in gestational diabetes. Cochrane reviews and randomised trials. ANZJOG, 2016.
19. NICE. Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. National collaborating centre for Women’s and Children’s Health, 2015.
20. Horvath K, Koch K, Jeitler K et al. Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis. British Medical Journal 2010;340:1395-413.
21. Alwan N, Tuffnell D, West J. Treatments for gestational diabetes.Cochrane Database of Systematic Reviews 2009;3:CD003395.
22. McClean S, Farrar D, Kelly CA, Tuffnell D, Whitlaw D. The importance of glucose tolerance testing after pregnancies complicated by gestational diabetes. Diabetic Medicine 2010;27:650-4.
23. Holt RIG, Coleman MA, McCance DR. The implications of the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria for gestational diabetes. Diabetic Medicine 2011;28:382-5.
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