Looking after women with type 1 and type 2 diabetes in pregnancy: the latest research
Pregnancies complicated by diabetes are on the increase and pose risks for mother and baby. The role of diabetes technology in improving outcomes in these pregnancies was under discussion at ‘Revolutionising Diabetes Care: Celebrating 100 Years of Insulin Therapy’, a recent online conference organised by The Royal College of Physicians and Surgeons of Glasgow (RCPSG). Dr Susan Aldridge reports.
Before the advent of insulin, women with type 1 diabetes and their babies simply did not survive. Then, in 1933, one of the first studies of the use of insulin in pregnancy noted a preponderance of ‘giant babies’ – some weighing more than 5kg – in a cohort of 608 infants born to 155 mothers with diabetes.
Now known as large-for-gestational-age (LGA) babies, 63% of the babies born in this study were affected by this complication. Writing in the New England Journal of Medicine in 1941, Dr Martin Nothmann said, “Diabetes is more unfavourable for the child than the mother – in this regard, insulin cannot accomplish much.”
“The most recent snapshot [from the National Diabetes in Pregnancy audit (NPID)] tells us that today we have one in 10 pregnancies with potentially preventable serious adverse outcomes – that is, still birth, newborn death or birth defect, and this applies across both type 1 and type 2 diabetes,” said Helen Murphy, Professor of Medicine at the University of East Anglia and Chair of NPID. “Early-onset type 2 diabetes has been increasing, so we are now seeing more women in pregnancy with type 2 than those with type 1.”
In 2002/03, at the time of the first Confidential Enquiry into Maternal and Child Health (CEMACH) report, there were 1707 type 1 diabetes pregnancies and only 652 affected by type 2, whereas in 2019-2020, there were 4175 type 1 and 5085 type 2 pregnancies. And this is occurring at a time when NHS maternity services are already stretched.
“What’s also really important is the different patient characteristics,” said Professor Murphy. Women with type 1 are predominantly White, while those with type 2 are more likely to be from ethnic minority groups and are much more likely to live in areas of deprivation. The data shows that 42% of type 2 pregnancies occur among women living in the most deprived areas, while just 5% live in the least deprived areas. “It is vital moving forward that we plan our services such that resources are targeted to these high-risk women,” said Professor Murphy.
Focus on maternal glucose levels
Maternal glucose levels at the time of conception are crucial in determining the outcome of a pregnancy. The National Institute for Health and Care Excellence (NICE) recommends that all women with diabetes aim for an HbA1c of 6.5% (48 mmol/mol). “We know, however, that very few women achieve this,” said Professor Murphy. “But as HbA1c rises – from 7% [53 mmol/mol] and above – there is a sharp increase in congenital malformations among infants born to women with type 1 and type 2. So the single most important message for anyone looking after women of reproductive years is that they should be offered access to safe, effective forms of contraception until HbA1c is as good as it can get for pregnancy.”
Taking adequate folic acid and achieving target glucose levels are key markers in preparing for pregnancy. Half of all women with type 1 diabetes take 5 mg folic acid, compared with only 20% of those with type 2 diabetes. With HbA1c, 15% with type 1 diabetes reach the glucose target and just over 35% with type 2 diabetes. “This means that 65% of those with type 2 do not,” said Professor Murphy. “Most are on metformin, so they are diagnosed but not treated to target and only 18% of these women of reproductive age are treated with insulin before pregnancy. That is something that seriously needs to change.”
Which women are most likely to achieve their glucose target? For type 1 diabetes, it is women in the 35-44 age group and those with the shortest duration of diabetes, therefore having some endogenous insulin secretion. Younger women, those living in deprived communities, those with longer duration and those with higher BMI are the least likely to get to target. The data are similar for type 2 diabetes, although deprivation has less of an impact as most of these women already live in deprived communities.
Professor Murphy then turned to the effects of glucose on obstetric and neonatal complications. If HbA1c is more than 6.1% (43 mmol/mol), there’s a high risk of preterm delivery, which is similar for type 1 and type 2 diabetes. Also, 50% of women with HbA1c between 6.1-6.5% (43-48 mmol/mol) will have a baby that is LGA. “So the key message from this data is that we need to target tighter glycaemia in the second half of pregnancy,” she said. “And, of course, to do that, we need better insulins and better methods for glucose monitoring.”
Rates of stillbirth and neonatal death have decreased in recent years. However, there is concern that stillbirths in type 2 pregnancy may be starting to increase, which needs to be watched very closely in the next few years. “The key modifiable factor in perinatal death in type 1 and type 2 is having HbA1c more than 43 mmol/mol,” said Professor Murphy. Data show a higher risk for women with type 2 diabetes, suggesting that they are particularly vulnerable to above-target glycaemia during the second and third trimesters. If a woman can get to target by 24 weeks, it will significantly reduce the risk of stillbirth.
Continuous glucose monitoring
Using better technology to monitor glucose does help women personalise their insulin delivery. Professor Murphy was involved in the CONCEPTT trial, which compared real-time continuous glucose monitoring (CGM) with fingerstick glucose monitoring in women with type 1 diabetes during pregnancy or pregnancy planning. CGM led to a 7% increase in time in range (TIR), equivalent to an extra 100 minutes a day in range throughout the pregnancy.
The outcomes showed that these small improvements in glycaemic control led to significant benefits for the infant, with reduced rates of LGA, neonatal hypoglycaemia and neonatal intensive care unit admission. “It is this data that led to the UK being one of the first countries in the world to offer CGM to all women with type 1 diabetes to help support them to reach their glucose target and improve neonatal outcomes,” said Professor Murphy. “We are just beginning to see the impact of that as it rolls out across the NHS. We now have national audit data for over 1,000 real-world CGM users and we’re optimistic that some of these benefits we’ve seen in the randomised trial will be replicated in this real-world data set.”
During this rollout, education and support of healthcare professionals is key to helping women understand the importance of reaching their glucose targets. “We have learned that women find these glucose targets, particularly TIR, very intuitive and accessible and, of course, this data sits on their own phones, so they have it to hand,” said Professor Murphy. A series of webinars has been developed to support this rollout, focusing on the use of CGM at the various stages of pregnancy, including delivery and in the postnatal period.
Targets for hyper- and hypoglycaemia are now firmly established in clinical practice for managing women with type 1 diabetes. For TIR (3.5 to 7.8 mmol/l), this should be 70% of the time with less than 25% above 7.8 mmol/l and less than 1% below 3 mmol/l. Women with type 2 diabetes may benefit from aiming for 90-100% TIR.
Mean glucose is also important, where the target should be 6-6.5 mmol/l. ”Achieving these targets, even with the latest CGM and insulin pumps, is hard work and, in my view, automated insulin delivery will take over from insulin pumps and we will have CGM linked to an algorithm that is linked to insulin delivery,” said Professor Murphy. “This will eliminate a lot of the work for women with type 1 diabetes, although with the systems that are available today, carb counting and meal bolusing are still required.”
Hybrid closed loop in pregnancy
Professor Murphy has also been involved in trials of the CamAPS-FX hybrid closed loop system – developed by Professor Roman Hovorka’s team in Cambridge – in type 1 diabetes pregnancy. These have produced some very promising overnight and 24-hour data and the results will be published in the next few months. “What I can share with you today is our experience of supporting women using closed loop,” she said. “Not all women will be able to achieve perfect glycaemic control but, in our experience, with the right education and support, most women should have the same results as outside of pregnancy, which is an increase of 7-10% in TIR.”
Working with colleagues from Scotland, Professor Murphy’s team has done a series of interviews with healthcare professionals looking after women using closed loop in pregnancy. “This is coming and it’s coming soon,” she said. “We’re going to see far more women choosing to use automated or hybrid closed loop systems, so we are starting to look at what we need to do, as healthcare professionals, to roll this out across the NHS.”
The first step in this roll-out is support and education of diabetes teams. One of the messages from the above survey is that all women should be offered these technologies, wherever they’re being looked after. “That does present some challenges, so we need to upskill the workforce right across the UK,” Professor Murphy said. “However, I’m optimistic because we managed to roll out CGM in the real world during the pandemic and I do think that, in the next few years, we’re going to see the rollout of hybrid closed loop for women who are either pregnant or planning a pregnancy.”
Even in the absence of trial data – which will follow shortly – qualitative data from women using the systems is so powerful, she continued. “We’re getting reports of women who are able to stay in paid employment and are having better relationships with healthcare professionals. Most important of all, they’re finding that using this technology allows them to enjoy the pregnancy experience and achieve better glucose outcomes.”
This is illustrated by the words of one woman interviewed, who took six years to become pregnant. “The 246 days of pregnancy meant 17,000 units of insulin, 216 jabs and 70% TIR,” she said. “The technology I was able to use throughout made the journey as stress-free as possible!”
“The challenge for us is to make sure that we can deliver these technologies to all women to improve their experiences of pregnancy and achieve the best possible outcomes for their babies,” Professor Murphy concluded.
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.