Is precision prevention the way forward for gestational diabetes?
Gestational diabetes can have a serious impact on the health of both mother and baby. But according to a recent review in Diabetologia,there is scope now for a more precise approach to its prevention based on interventions tailored to a woman’s individual risk. Dr Susan Aldridge takes a closer look.
Gestational diabetes mellitus (GDM) affects 10 to 25% of all pregnancies worldwide. It is associated with increased risk of adverse health outcomes for both mother and offspring, so prevention is important. However, the aetiology of GDM is complex and multifactorial, involving both genetic and environmental influences. Non-modifiable risk factors include Asian or Hispanic ethnicity, advanced age and a family history of type 2 diabetes. There are also many potentially modifiable risk factors involved in the development of GDM relating to lifestyle and environment, including pre-pregnancy obesity, gestational weight gain (GWG), diet and physical activity, smoking and having closely spaced pregnancies.
Researchers at Louisiana State University and Harvard Medical School say there is now a big opportunity to develop and validate a tool to assess GDM risk at an individual level and, thereby, to direct those at greatest risk to more precise - and maybe earlier - interventions. To this end, they have reviewed research into lifestyle interventions intended to prevent GDM.
A meta-analysis in 2015 looked at six trials, covering 1309 women and involving meal replacement or promotion of healthy eating with, or without, counselling, and found no significant reduction in GDM risk. But when the analysis was stratified by body mass index (BMI) across three of the trials, a significant reduction was found in those who had overweight or obesity. Then a 2018 meta-analysis, including five additional trials, did find a significant reduction in risk. But for studies that specifically included, or stratified, women with overweight or obesity, dietary intervention no longer produced a significant reduction in GDM risk. This was confusing – and the authors speculated that maybe the interventions had been started too late in the pregnancy for those with overweight or obesity.
In short, overall findings from these meta-analyses suggested that dietary intervention trials did not result in a physiologically relevant reduction in GWG to reduce GDM risk. However, the 2015 meta-analysis focused on dietary manipulation as a treatment to prevent GDM, while the 2018 study looked at appropriate GWG as its primary outcome, with prevention of GDM as a downstream benefit. Future studies should focus on timing of diet-based interventions for women with pre-pregnancy overweight/obesity and should look at how other characteristics can explain the variability of GDM-risk reduction in response to these interventions.
Physical activity interventions
It’s well known that physical activity decreases insulin resistance and increases skeletal muscle glucose disposal, so could help reduce GDM risk. A 2018 meta-analysis of 26 trials, including 6934 women, found that prenatal exercise significantly reduces the odds of GDM. A further meta-analysis of 10 trials, the same year, confirmed this finding. However, in those studies specifically including or stratifying women with overweight or obesity, physical activity interventions did not reduce GDM risk. In the following year, a meta-analysis of eight trials, including 1441 women with overweight or obesity, found that GDM incidence was 24% lower in those in the exercise intervention group.
These meta-analyses suggest that physical activity interventions may have differential impacts, depending upon pre-pregnancy body weight. Lack of efficacy might also be due to inability to limit GWG through physical activity alone. Answers may come from a trial currently underway focusing on pre-conception weight loss in women with previous GDM to see whether a behavioural intervention that includes physical activity might be effective in reducing the risk of GDM in a subsequent pregnancy.
Looking at the details of a physical-activity intervention, various components have the potential to reduce GDM risk. These include moderate-intensity bouts of 40 to 60 minutes, performed at least three times a week and including aerobic exercise, resistance training or a combination of the two. There is also evidence for completing at least 80% of the bouts and maintaining a pre-pregnancy physical activity programme throughout pregnancy being protective against GDM, especially among those who have overweight or obesity.
Behaviour-change techniques, including goal setting, self-monitoring and self-regulation can also help with weight control in pregnant women. A recent systematic review of 43 studies, covering 19,752 women, looked a pre-natal behavioural interventions aimed at controlling GWG. Most were multi-modal interventions including at least one structured element, such as supervised exercise or a dietary programme, with behavioural counselling, or behavioural counselling alone. Provider-patient contacts ranged from fewer than two to greater than 12.
These multi-modal interventions were significantly associated with lower GDM risk and those with the highest efficacy were the ones with more than three provider-patient contacts, highlighting the importance of support for behavioural change. Also of note here is the Finnish Gestational Diabetes Prevention Study, which showed that the inclusion of individualised counselling for diet, physical activity and weight control from trained study nurses, along with one group meeting with a dietitian, reduced GDM incidence compared with usual care (13.9% versus 21.6%).
Various analyses have looked at whether it’s better to try diet or physical activity alone or in a multi-modal intervention to reduce the risk of GDM. These found that the multi-modal approach is not more effective, maybe because having too many components to an intervention is overwhelming for women who already have a lot going on with the pregnancy itself. Further research is needed into whether multi-modal approaches have more impact if implemented pre-conception.
Limitations of current GDM research
Most trials have not looked at the efficacy of interventions started prior to conception or earlier in pregnancy. One review did find two studies that started a physical activity intervention between 10 and 14 weeks of gestation, as opposed to the more usual 16 to 20 weeks. These ‘early pregnancy’ interventions did indeed halve GDM risk compared with usual care. Earlier intervention allows longer involvement with a programme and more opportunities for sessions to be completed.
So far, interventions have been rigid in their prescription throughout the programme. Gestational diabetes research has not caught up with the real-time monitoring of behaviour change that is possible now through e-health technology and wearables, such as continuous glucose monitoring (CGM) and apps. But these are being used increasingly in the area of weight management and type 2 diabetes. These just-in-time adaptive interventions (JITAIs) use information collected in real time to tailor the intervention to each individual.
The future of GDM prevention
The research so far suggests that there is an urgent need to move from a ‘one-size-fits-most’ to a more personalised approach taking into account a pregnant woman’s individual risk factors, behaviours and socio-economic situation.
When it comes to assessing individual risk, early pregnancy screening is needed to see if a woman has a high-, medium- or low-GDM risk. Risk-prevention tools should look at a wide range of characteristics, such as glucose metabolism and insulin sensitivity, and try to include novel biomarkers from metabolomic, genetic and microbiome studies. Although there isn’t yet sufficient evidence for the benefits of screening and treatment of GDM in early pregnancy, developing effective algorithms to identify those most at risk will help to better target approaches to reduce the risk of GDM development and, in turn, pregnancy, birth and postpartum complications.
These risk-prediction tools could be paired with lifestyle intervention RCTs, so that we can start to understand how different intervention approaches can benefit women based on their risk profiles. Monitoring response to an intervention via JITAI is another opportunity for research. For instance, if CGM shows a positive response to an exercise intervention, it could then be further adapted to refine the exercise dose, modality and intensity. Also, JITAIs based on other devices, like wearables for physical activity and sleep tracking, could provide real-time information for viewing by clinician and patient to further tailor the intervention throughout the pregnancy. And as new diet and physical activity JITAIs are developed, other factors, like psychological readiness to change, access to food and cultural food choices, can be included in future GDM-prevention interventions.
Earlier intervention is another area to explore for GDM prevention. Currently, GDM testing occurs at 24 weeks and in previous research interventions did not usually start before 16 weeks. This means a window of opportunity is being missed – a longer intervention, starting earlier, may have more of an impact.
In conclusion, the authors of this review welcome the emerging field of precision prevention for GDM and make a number of proposals to help move it along. First, the development and validation of algorithms to accurately prevent GDM risk will identify those women who have most to gain from a prevention programme. Next, this risk should be matched to new intervention approaches. Finally, modern JITAIs, incorporating innovative technologies, should be developed to continuously assess individual responses to GDM prevention interventions. Such developments could go a long way towards improving outcomes for both mother and child in a pregnancy at risk of GDM.
To read this paper, go to: Sparks JR, Ghildayal N, Hivert M-F, Redman LM. Lifestyle interventions in pregnancy targeting GDM prevention: looking ahead to precision medicine. Diabetologia online 12 February 2022.
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Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.