Managing pre-existing diabetes prior to and during pregnancy

There is more evidence for preconception care in diabetes than, I think maybe, for any other condition. It is absolutely without doubt that high-quality preconception care improves outcomes.

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Medical care before and during pregnancy is highly individual. Today, on the Australian Prescriber Podcast, we are highlighting the important aspects of managing pre-existing diabetes prior to and during pregnancy. I'm Dr. Laura Beaton, your GP host for this episode. I'm joined by Professor Leonie Callaway, who is a general and obstetric physician, and the Director of Research at the Royal Brisbane and Women's Hospital. She's written about this topic along with Dr Fiona Britten for Australian Prescriber.

While only about half a percent of all pregnancies in Australia have diabetes as a pre-existing condition, the consequences of suboptimal glycaemic management can have profound impacts on maternal and fetal health. So, while it's a bit of a sombre place to start, Leonie, could you please take us through what we are trying to avoid.

That is sombre. So, I guess that there is more evidence for preconception care in diabetes than, I think maybe, for any other condition. It is absolutely without doubt that high-quality preconception care improves outcomes. The main concern is that if in the first trimester the growing fetus is exposed to hyperglycaemia, then the risk of congenital anomalies is very high. That is really proportionate to the severity of the hyperglycaemia.

Also, glucose management in pregnancy is directly related to a range of other complications, including growth with the fetus, both small for gestational age and macrosomia [large for gestational age], preterm birth, and also maternal complications such as pre-eclampsia. All of those complications are improved by detailed attention to glucose management prior to and during pregnancy and, also, at the time of delivery.

And your article really does highlight the importance of preconception care for all people, not just those with diabetes. So, what are the differences in preconception advice for women particularly with pre-existing diabetes?

I think when you're looking after people with pre-existing diabetes, or any pre-existing medical condition, it’s easy to get into all of the complex parts of looking after the medical condition and to forget all of the basic things. So, we do often see people that have been cared for a complex medical condition, and the basics have been forgotten. The basics for all women considering having a baby, to stop smoking, good nutrition, general lifestyle issues, advice around alcohol, and also appropriate cervical screening to make sure that people don't have abnormalities in their cervix that need attention prior to pregnancy, and also that vaccinations are up to date, and that sexually transmitted diseases screening is appropriately done. It needs particular mention because it’s easy to forget the basics for any complex woman. With diabetes, there’s really a few considerations. Try and ensure that there’s really good glucose control, however that’s achieved.

The second is to make sure that women are not taking drugs that they shouldn’t be taking in the first trimester. The key concerns in this are lipid-lowering therapies, particularly the statins, but all lipid-lowering therapies, the ACE inhibitors, and the AII receptor antagonists. That group of drugs that get used for hypertension management, renal disease management and hyperlipidemia, all need to be considered as to when they need to be stopped or changed over. There’s also a range of medications that women may be on for type 2 diabetes, particularly some of the new medications, semaglutide and so forth, that currently don't have clear evidence that they are safe in pregnancy. That may well emerge.

Then for people that have had diabetes, we need to think about "Are there complications that might impact on their pregnancy, that need to be appropriately assessed prior to pregnancy?" In women with type 1 diabetes, we need to consider the risk of other autoimmune disease. "Could this woman possibly have coronary artery disease, underlying renal disease, diabetic retinopathy, diabetic autonomic neuropathy, or poor vasculature to her feet?" For women with type 2 diabetes, essentially all of those complications remain the same except for the risk of associated autoimmune diseases. Perhaps, in women with type 2 diabetes, whether there might be a risk of obstructive sleep apnoea, fatty liver disease. So a very detailed clinical history examination and appropriate investigations is required. If any of those issues are identified, they really need to be managed and considered and counselled about, prior to proceeding with a pregnancy.

The other thing that’s really important and is easy to forget is the health of the father is also relevant. While the father might not have diabetes, nonetheless, making sure that sperm quality is as good as it can be is an important part of helping to make sure that a pregnancy is healthy. So, it’s important to remember to speak to the male partner with reminders about alcohol, occupational exposures, a consideration of appropriate drugs.

A pertinent reminder to never forget the basics. So, we’re covering all our usual things for preconception care, but also some extra investigations for complications and comorbidities of diabetes. Is the timeframe about, ideally, 3 months of optimal preconception care with a target HbA1c of about 6.5%, or lower, before planning conception?

That's correct, Laura. But really, some women take a bit longer than that to get good glucose control. So, I really like to see people 6 or 12 months prior to consideration of pregnancy, if it is possible. If there’s a lot of work in improving that glycaemic control, or needing to do detailed renal baseline investigations or coronary angiograms, you’ve actually got plenty of time to do that.

The use of newer technologies, like continuous glucose monitoring, has this changed, at all, the management of diabetes and pregnancy in your practice, or when you’ve been speaking with patients about their experiences?

I absolutely adore continuous glucose monitoring (CGM), Laura. Obviously, it was introduced because there’s compelling randomised controlled trials that show that it really improves the situation, so that’s why it is now funded. The information that we’re suddenly able to obtain from looking at CGM recordings is so interesting. For example, if you’ve got a toddler that’s been up all night with a fever or throwing up, and you’ve had absolutely no sleep, the impact that that has on a woman’s glucose management is so significant. It has nothing to do with what they’ve eaten or what they’ve done in terms of exercise. Not getting a good night’s sleep and having the stress of a little one, who’s unwell, is really, really bad for your glucose control. So, I think what CGM has done is allow us to be much more holistic about what is going on. Having fights with your partner on a regular basis, being exposed to domestic and family violence, these things really interfere with good glucose management.

What I’ve discovered with CGM is that to get good glucose control, mental health issues really need to be attended to. Sometimes the solution to hyperglycaemia is to refer people for couples counselling to try and improve the quality of their relationships. So, these broader range of considerations about how we help people to live healthy lives and the interesting observations that we can come up with from looking at continuous glucose monitoring, I think it's just so profound.

When I was reading your article, it looks like we’re not just trying to make sure that we are avoiding hyperglycaemia, but actually having very minimal, or very low, times of hypoglycaemia. What’s the issue with hypoglycaemia, pre and during pregnancy?

People with hypoglycaemia become unconscious and have seizures. We know that the hypoxia associated with that is definitely not a good idea for pregnant women. Also, hypoglycaemia really results in great difficulty in managing glucose control because all of the counter regulatory hormones that kick in following a hypoglycaemic episode then push the sugars really high. Then, you just end up in this vicious cycle of rebound hyperglycaemia and hypoglycaemia.

So, there’s a safety component to it. Most of these women are driving, so we don't want hypoglycaemic episodes while they’re driving. We just don’t want periods of hypoglycaemia for the fetus to be exposed to. We certainly don’t want the maternal complications of hypoglycaemic unconsciousness or seizures, and all of the physiological consequences of that.

Your article goes through the different complications that we’re looking at, preventing, and closely screening for. Would you mind running us through those?

Yes. So, I suppose that they really fall into maternal complications and fetal complications, Laura. The complication that we’re really concerned about with women with type 1 and type 2 diabetes is the development of pre-eclampsia. So, this really drives a lot of very close surveillance. We recommend that everyone with diabetes prior to pregnancy is given aspirin. There’s good evidence that this helps to reduce the risk of pre-eclampsia. Because of the high risk of pre-eclampsia, the baseline assessment of urine protein, creatinine ratio, renal function, platelets, and liver function tests, is very important. We need to know whether any of those things change during pregnancy. Then, the other things that are obviously complications are the issues of premature contractions, preterm birth.

In terms of fetal growth, there’s 2 issues, really. One is that you can end up with intrauterine growth restriction because the placenta is not working really well, in which case careful surveillance for ongoing fetal growth and fetal wellbeing and decisions about how long that pregnancy should continue for in terms of fetal movements and so forth is important. And then, there’s obviously the macrosomia issue. I think that, increasingly, we’re guiding our decision-making about the tightness of glucose control based on how fetal growth is going. If the baby is small, we’re perhaps not being quite so absolutely obsessively strict about very, very tight glucose control. We’d certainly be very concerned about avoiding hypoglycaemia. On the other end, if you've got a macrosomic baby, you really want to make sure glucose control is as good as you can make it.

Then, I propose the other things that can happen are just in terms of the complications of type 1 and type 2 diabetes. So, pregnancy is a metabolic stress test. It’s a significant physiological stress test on women’s cardiovascular and metabolic systems. So, some women have their fatty liver disease unmasked during pregnancy. Particularly, women with type 2 diabetes can have some abnormalities in their liver function tests throughout pregnancy.

Renal dysfunction can become a problem if there’s some underlying renal dysfunction prior to pregnancy. Cardiovascular function, exercise tolerance, and how a woman is going from a cardiovascular perspective, and obviously chest pain, palpitations, and all of those sorts of symptoms, need to be taken really, really seriously in this cohort because we don’t ever want to be missing unmasked cardiovascular disease with the physiological stresses of pregnancy. I don't know if I’ve caught them all, Laura.

You’ve covered off so many. Earlier, you did mention the importance of driving safety with hypoglycaemia. It was great to remind myself. Also, thinking about hypomanagement, glucagon is safe in pregnancy, and that’s really important. I guess one of the things you also mentioned in your article’s around diabetic ketoacidosis and sick-day planning, and potentially access to ketone strips.

Yes. Laura, I think that a lot of people don’t have a clear sick-day management plan. That is really something that needs to be revisited. Absolutely, as you say, you need to make sure that people have got access to glucagon and have got a hypoglycaemic management plan, and that someone else in the house preferably also knows how to use the glucagon pen, and the glucagon pens are all in date. It is really important to remind women and document that you’ve discussed the driving safety legislation. In terms of sick-day management, yes.

I think one of the things about pregnancy that’s important to highlight is that some women are even more prone to flicking into ketoacidosis when they’re pregnant. Their metabolism’s already doing a lot of work. So, a little bit of extra care about monitoring for ketones during pregnancy and contacting healthcare providers and implementing that sick-day plan during pregnancy is really important. We make the point in the article that it is possible to develop euglycaemic ketoacidosis. So, measuring ketones is an important issue if people are feeling unwell.

Maybe, if it’s all right, we’ll finish off today by moving to postpartum care, which sounds like it’s got many of the principles of preconception care that we spent a lot of time talking about. Earlier, you spoke through all of the medications that we really need to either consider or cease while planning pregnancy, or pregnant. When someone's breastfeeding, are there any medications that are commonly used in diabetes that are actually safe to recommence, or are we really waiting until breastfeeding is completed before recommencing?

So, if you have postpartum hyperglycaemia, establishing lactation can take a little bit more time. We also know that there’s delayed lactogenesis in women who have larger bodies and also have type 2 diabetes. So, there’s a lot of support required in this. I think it’s really support that’s worthwhile because we know that breastfeeding is very helpful for women in terms of long-term health improvements.

In terms of drugs, I would not recommend the restarting of any of the lipid-lowering therapies or statins until breastfeeding is absolutely completed. However, many of the ACE inhibitors certainly can be reinstituted during breastfeeding. So, there’s long-standing safety data for a number of those. I typically use captopril or perindopril, although I know other centres use enalapril. So, we’re talking about the kind of old-fashioned ACE inhibitors during breastfeeding. Particularly for women who've got issues with hypertension, or we’re trying to provide renal protection, then reintroducing those medications is a really good idea. We don’t have any evidence about the new group of the GLP-1 [receptor] agonists during breastfeeding, so I would not restart any of those medications. Metformin can continue to be used for women with type 2 diabetes, and obviously insulin is fine.

So, decisions do need to be made about how we manage glucose control. I think that glucose management during breastfeeding is also really important because maternal hyperglycaemia influences the composition of the breast milk. So, whilst there’s not a lot of research about this, it does seem to make sense to me that we should not take our eye off the ball about really good glucose management while breastfeeding is going on. So, I feel like that’s an area that general practice can make such a major contribution in supporting, encouraging, and problem-solving breastfeeding difficulties, and referring women to appropriate lactation support where there’s any difficulties.

Thank you so much for taking the time to talk to me today. This is such a highly specialised topic. It has been really valuable to consider all of the broad aspects, and also, how we can all support women with pre-existing diabetes with their reproductive health.

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The full article we spoke about today is available for free on the Australian Prescriber website. The views of the host and the guests on this podcast are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Leonie Callaway and Fiona Britten are authors of the Australian Diabetes in Pregnancy Society 2020 Guideline for Pre-Existing Diabetes in Pregnancy.