COMMENTARY

Managing Pregnancy in T1D: 'One of the Hardest Things We Do'

Anne L. Peters, MD

Disclosures

March 11, 2021

This transcript has been edited for clarity.

One of my very favorite topics is the management of pregnancy in women with preexisting diabetes. This is one of the hardest things we do — certainly one of the hardest things women do — but it ends up with a wonderful outcome. I want to reinforce what we know and talk about continuous glucose monitoring (CGM).

First, let's talk about pregnancy planning. Women with diabetes have about the same rate of unplanned pregnancies as women who don't have diabetes. I'd like to think it was less, but [unplanned] pregnancies happen.

For anyone who I think is going to become pregnant or is likely to become pregnant, I start her on prenatal vitamins. This might be someone who just got married and says, "I want to have a baby in a year or two." Those are the women that I often find getting pregnant before they know it, so I have them on prenatal vitamins.

Second, when I'm working with somebody who is planning on pregnancy in the near future, I make sure she gets an eye exam, I check her renal function, and I evaluate her to be sure that she is otherwise healthy.

Then, I start them on CGM if they're not already on it. I do this partly because I think the data are much easier to analyze when they can come seamlessly into my office through the CGM, but also because I have my patients rely on CGM so much during pregnancy. CGM is not yet approved in the United States for use during pregnancy. I'm going to talk about that more in a minute. But certainly, it's a tool I use often.

Finally, I switch them off medications that aren't safe for use in pregnancy. If they're on antihypertensives or a statin, I make sure that we change those around so that they're ready to get pregnant.

Pregnancy Targets and the Problem With Hybrid Closed-Loop Systems

Now let's review the pregnancy targets. These seem frightening to women who aren't yet pregnant, but I tell all of my women patients that they're completely possible. And frankly, the motivation of pregnancy helps women get down to these values. The fasting glucose is 70-95 mg/dL. The 1-hour glucose is 110-140 mg/dL, the 2-hour glucose is 100-120 mg/dL, and the A1c target is < 6%. This basically means that you want women to be below 140 mg/dL most of the time and their fasting glucose to be below 100 mg/dL — but I don't always quite get there.

One of the reasons I like CGM data is because we can look at CGM targets. In particular, we look at the time in range. This is a different range, of 63-140 mg/dL. Our goal is to have women at 70% or more in this range.

This is a little tricky because you don't want someone to have a time in range of 100% but be at 130 mg/dL all the time; you want that fasting and overnight blood glucose level to be lower than that. So, it's not just the time in range. To some degree, it's the time in range by time and day.

The point is clear. You really want women to try most of the time to keep glucose levels, particularly postprandially, to less than 140 mg/dL. There's going to be an occasional blip up because that's just human, but it's very important to really stress these ranges.

Another thing that's important is that hybrid closed-loop systems, as they stand now, basically don't work in pregnancy because their targets are higher than this. Women may have issues trying to keep in these lower ranges with the hybrid closed-loop system shutting off insulin delivery when their glucose levels are, say, 80 mg/dL overnight, which is a perfectly fine glucose level for pregnancy.

Until these systems give me the ability to adjust the target ranges, I [will continue] taking women out of the hybrid closed-loop mode and have them manually adjust their doses. In general, that means floating up their basal rate manually when their glucose levels start going up after eating, and then shutting them off or reducing them after eating so they don't develop hypoglycemia.

Changes in Insulin Sensitivity, Insulin Resistance

One of the most challenging parts of pregnancy is how insulin sensitivity and resistance change throughout the duration of the pregnancy. Early on in pregnancy, I can't really predict what will happen. People will say to me that their glucose levels are just more unpredictable. Some women will go lower very early on and some a bit higher.

Usually between 9 and 14 weeks, there will be a decrease in the insulin requirement; people will be more sensitive to insulin. That's a period of time in which episodes of hypoglycemia, particularly severe hypoglycemia, are more common. It's very important early in pregnancy to train the patient's partner in the use of glucagon and make sure they have glucagon at home.

As the pregnancy progresses and gets to about 16 weeks, you start to see a marked increase in insulin requirements due to the insulin resistance of pregnancy. As it progresses further, you're going to see more stress postprandially. You're going to see more of an increase in postprandial glucose levels. Our women need to work very hard to bring those levels down.

It's very important that people work with a dietician and a diabetes educator. I don't know what I'd do without my team. Pregnancy is the one place where management of diabetes is absolutely a team effort.

At about 37 weeks, you may see a flattening of insulin requirements or maybe even a slight decrease. That's expected. If you see a sudden marked decrease in insulin requirements, then that can be a sign of fetal and placental insufficiency. At that point you want to contact the obstetrician and discuss testing to see if there are any issues related to fetal distress or the placenta not working adequately.

Finally, immediately postpartum, once the placenta is gone, you're going to see a marked reduction in insulin requirements. The doses of insulin after delivery can drop to as low as half of the pre-pregnancy needs. I generally write down on a piece of paper what the pre-pregnancy insulin doses were for the patient and then go below that just a bit to make sure that they don't go too low.

Then, the woman's life is going to change. She won't be sleeping like she normally does. She'll likely be breastfeeding. All of those things will change the patterns of insulin delivery.

CGM in Pregnancy

I'm going to briefly discuss the CONCEPTT trial, which was the clinical trial that really showed us the utility of using CGM in pregnancy. This was a multicenter study involving women between the ages of 18 and 40 who had type 1 diabetes.

There were two groups of women: those who were 13 or fewer weeks pregnant — early in pregnancy — and those who were planning pregnancy.

These individuals were randomized to CGM plus self-monitoring of blood glucose (SMBG) or SMBG alone. The individuals on CGM were told to test their blood sugar seven times a day, so they were doing SMBG. I was told when talking to some of the study investigators that the women didn't test their glucose levels a full seven times a day; they tested them less often because they had the CGM. But this was a part of the study; it wasn't CGM without SMBG. SMBG was certainly encouraged, particularly if there was a discordance between the CGM data and what the patient thought they might be in terms of their true blood glucose levels.

The primary outcome was a change in A1c. In this study, there was only a small change in A1c between the CGM group and the SMBG group. However, there was a significant increase in time in range with CGM — 68% vs 61% — which was very statistically significant.

Even more important, neonatal outcomes were improved. There was a lower incidence of large-for-gestational-age infants. There were fewer neonatal ICU visits lasting more than 24 hours. There were fewer episodes of neonatal hypoglycemia and a reduction by 1 day in hospital length of stay for the babies.

CGM really helped improve outcomes in the women who used it compared with those who were just on SMBG. There was, interestingly, no benefit of CGM seen in women who were planning pregnancy. Everybody got their A1c somewhat better while planning pregnancies, but the real improvements in time in range and A1c were seen in the women who were pregnant or when they became pregnant — and then they did well subsequently.

I think the CONCEPTT trial is a really good study in terms of showing us the benefits of CGM in pregnancy. We need to remember that we need to encourage women to really stick to the tried-and-true SMBG if there are any concerns about the CGM not being accurate, issues getting sensors, or whatever.

I'm really encouraged about what we can now do in terms of pregnancy in our patients with preexisting diabetes. I do want to stress the need for women to have that ophthalmologic exam at the beginning, maybe during pregnancy, and potentially after pregnancy — particularly if the A1c starts high and then goes down over the course of the pregnancy. I've certainly seen worsening of retinopathy.

The other question I'm often asked is whether it's safe to use a medication like metformin in pregnancy. The data on that are sort of complicated, and I can't exactly figure out what's best. I prefer to just use insulin for management of patients in pregnancy. In some cases, the obstetrician suggests that we continue to use metformin, and I work closely with the obstetrician to do what is optimal for both mom and baby.

This has been Dr Anne Peters for Medscape. Thank you very much for listening.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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