Hello and welcome to New Concepts in the Diagnosis and Management of Diabetes in Pregnancy. I'm Dr. Chloe Zera. I'm an Associate Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and the Chief of Maternal Fetal Medicine at Beth Israel Deaconess Medical Center in Boston, Massachusetts. I'm the chair for today's session. It's my pleasure to introduce Dr. Eboni Carter, who is the Chief of the Division of Clinical Research at the Washington University School of Medicine, and Dr. Karthik Venkatesh, who's an Assistant Professor of Obstetrics and Gynecology at the Ohio State University Wexner Medical Center, the Ohio State University. Today, we're going to review screening methods and the most current diagnostic criteria for gestational diabetes. We'll discuss epidemiology and sort of patient concerns in pregnancy for both type 1 and type 2 diabetes and apply latest recommendations for diabetes technology in gestational diabetes and pregnancy in pre-existing type 1 and type 2 diabetes. I'll show you our quick disclosures. So our objectives today, I want, well, we want for all of you to understand the impact of social and structural determinants of health on the epidemiology and outcomes of diabetes and pregnancy. We hope that you'll be able to explore the trade-offs between GDM screening strategies. We're going to review the use of technology in the management of pre-gestational diabetes and help you develop an approach for improving delivery of preconception and postpartum care for women with type 1 and type 2 diabetes. I'm going to hand it over to Dr. Carter. Thanks. Thank you, Dr. Zara, and good afternoon, everyone. We're going to start off by talking about the epidemiology and the social determinants of health of gestational diabetes in this country. And so I think it is probably no surprise to this audience that rates of type 2 diabetes have increased over time. Here you see on this graph going from 2004 to 2012 to 2019, the diabetes has just exploded. And along with that, gestational diabetes tends to follow a similar path. We're in this graph starting at 2011 going up to 2019. We see that regardless of racial, ethnic group, the rates of GDM are increasing. But I want to draw your attention to the fact that the increase is not fair nor equitable across the population. We see that some groups in this graph that are segmented by Asian Pacific Islanders, Hispanic Latina patients, Black and White patients, that in some groups, the rates continue to be much higher. This is a paper by my colleague who is going to follow behind me, Dr. Venkatesh, because we know that the rates of disease are increasing. But what is happening with the actual adverse pregnancy outcomes that are related to gestational diabetes? So Dr. Venkatesh and his colleagues performed a cross-sectional study using US National Center for Health Statistics natality data. Now, this study included over 1.5 million patients. And I don't put this graph here for you to read it. I'm going to tell you the results. This is really just a reference document for later. So this looked at all of the GDM singleton pregnancies from 2014 to 2020 and saw that overall the rates of hyperintensive disorders of pregnancy, transfusion, preterm birth, and NICU admission significantly increased over that period. While there was some good news, C-section and rates of large for gestational age or LGA decreased. But once again, let's go back to the disparity. Across the board, Black patients had a much higher rate of adverse pregnancy outcomes with the exception of LGA. Indigenous Native American people were at higher risk for everything except C-section and small for gestational age. And we looked at the subgroup of the population that was Hispanic, Asian, Pacific Islander. They were at higher risk for maternal and neonatal ICU admission, preterm birth, and small for gestational age. So what is going on here? And I think that it's really helpful to look at this from the framework of the social determinants of health. So I borrowed this framework from Dr. Joya Crear-Perry because I think it's a really helpful way to look at things. So we often think about social determinants of health. Do you have access to good housing and education and healthy foods and all of the things that are required for us to thrive and to be healthy? Why are the social determinants of health not distributed fairly in this country? And you can't start there. You actually have to go down to the root causes, such as power and wealth imbalance. And let's go even a little bit deeper than that. Root causes like institutional racism, class oppression, gender discrimination and exploitation. And until we look at some of those root causes, then I would argue that it will be difficult to move the needle and to actually affect change. I like to look at these issues from a life course perspective. And so I want you to imagine with me my patient population, which is predominantly Black women who are living in North St. Louis City and County, where our rates of preterm birth, infant maternal mortality are completely inexcusable. And so if we think about a hypothetical healthy population, you're born and then you get pregnant, you take a little bit of a metabolic hit, but you're young, you're healthy, you return back to normal and you live your life and you never hit that threshold that defines diabetes. But let's think about my patient population. Let's say that you're born to a mom that has gestational diabetes. So you've taken a metabolic hit before you even got into this world. And then you hit your own reproductive years. And so once again, you take a metabolic hit with the pregnancy, but you're young and you're healthy. And I should add in this kind of hypothetical schematic, they actually cross the threshold to have gestational diabetes in pregnancy, but it resolves. But we see in later in life, the risk of type 2 diabetes tends to happen much sooner. And we're not talking 20 years. If you're just looking even five years after pregnancy, you see that the rates of type 2 diabetes are higher. And so what if as a goal, we could take patients who are living on this red line and push them down towards the black line so that hopefully they never get type 2 diabetes, or if they do, they're getting it when they're 80 and not when they're 48. And that's really what I've devoted my research program to. The slides are taking me patience because it's taking a minute to advance. I apologize. So let's turn our attention to screening. And what are the early screening strategies that we have? I'm taking this from the American College of OBGYN practice bulletin. And ACOG essentially recommends that we do early screening. So this is kind of like, you know, first prenatal visit, first trimester screening for patients who present with risk factors, such as a history of gestational diabetes in a prior pregnancy. And there's several other risk factors that are here in POC box one that I took directly from that ACOG practice bulletin that was published in 2018. And so what are we doing when we do early screening? Really, if you think about my patient population, once again, that largely is uninsured until they're pregnant, get emergency Medicaid, there are a lot of patients who probably have type 2 diabetes, never diagnosed, now they're pregnant, have access to, you know, ready medical care. And there are all these people with type 2 diabetes that's undiagnosed. So that's actually what we are trying to capture. And so in our resident notes, you know, they often write, you know, GDM, likely type 2 diabetes for these patients who are getting diagnosed earlier than our typical 24 to 28 week window. Now, I think part of the challenge with early screening is there is a lot of debate. So should we even be doing it? Does it even improve outcomes for patients? And a lot of the studies are kind of in conflict there and suggest that there might not be a benefit. I would argue that a lot of the studies are testing people still closer to 20 weeks, which is much later than you would want in an ideal world. But I would say that the professional society guidelines in terms of what to do and how you do early screening are kind of clear as mud. You can kind of do anything. So this is old, but I'm using this slide because I think it nicely puts together all of the differences in professional society guidelines. And so there's debate and whether we should be doing early screening or not. And, you know, if you do it, that you can use a hemoglobin A1C, you can use one-step testing, you can use a two-hour, like all of those are actually acceptable because the guidelines are, I think, clear as mud in this area. But I'm happy to report that there is more consensus when it comes to second trimester screening and the fact that we should be doing it universally. Even the most recent U.S. Preventive Services Guidelines from 2021 recommends that we should be doing screening between 24 and 28 weeks in pregnancy. But I think it's helpful as I present to you kind of what are our latest recommendations and screening guidelines for GDM to take a brief trip down memory lane. And I'm going to start with the HAPO study. So landmark study that was done to try to figure out what are the diagnostic thresholds that we should be using to diagnose GDM. And what did they come up with? You know, you see some of our common diabetes related outcomes in pregnancy, birth weight, primary cesarean section, hypoglycemia. And you see there are no clear-cut points. It's a continuum. So even if you pass your GDM screening test but you barely pass it, your risk of adverse outcomes is going to be higher. And so, you know, what do we do with that? Going forward, the IADPSG essentially came out with recommendations. And I feel like I'm about to go over my time. So I'm going to go through the history rather quickly and come to the point that essentially there is disagreement largely over whether we should be doing one-step testing with the two-hour or screening with a one-hour followed by a three-hour test for those who are greater than 130, 135, or 140 milligrams per deciliter depending on where you are and what you decide to do. So I think this lack of consensus makes it challenging. And I'm waiting for my other animations to come up here. All right, here we go. And so, what should we be doing? Should we be doing the one-step testing or the two-step testing? And so, there was a lot of debate about this, but there were two really well-done randomized trials by Hillier and Davis that came out about a year ago that I think really helps us in terms of what to do. And this is just a pictorial schematic of one versus two-step testing. And the fact of the matter is that the other thing about one-step testing is it's going to increase the number of patients diagnosed with gestational diabetes significantly. And what does this do at a population level? And the Hillier and Davis trial, two well-done randomized trials, really helped to put that to bed. And so, I'm not going to go over those trials specifically, but I do want to go over a meta-analysis that our group at Wash U published in the Green Journal last year that looked at, it was almost 700,000 patients in an international sample, just kind of pulling the results of all of the studies of one versus two-step testing. We looked at both randomized trials and observational trials. And when you put that data together, we see an interesting picture emerge. So one-step testing is associated with an increased risk of gestational diabetes diagnosis and treatment when you compare it to two-step testing, and that's no surprise. It comes with a modest reduction in large-purge gestational age and hypertensive disorders of pregnancy, but that is offset by a higher risk of cesarean section and neonatal morbidity. And I think that in medicine, when you get a diagnosis of GDM, do we do more stuff to you? We're going to test you more. We're going to do more things. And are all of those things, are they good? Are they actually improving outcomes at the population level? And so, I think the take-home points in terms of one-step testing versus two-step testing are mirrored here. And I think you could still debate it a little bit, but personally, for me, I think it's put to bed that in the short term, it appears that two-step testing is probably the better strategy at the population level. But I wrote this editorial with Camille Poe, and in it, we say that the latest evidence in terms of the RCTs that have come out, I think, put to rest the question of one versus two-step testing for now. I think two-step testing has won the round. However, what does it mean for long-term risk and morbidity? We don't know, and that question is really not answered and outstanding. And so, I think that additional studies are going to need to be done to follow up those patients to see in the long term, does it matter what we're doing in pregnancy for the patient's long-term cardiometabolic health? And so, with that, I'm going to turn it over to my colleague, Dr. Venkatesh, to take it from here. Thank you. So now, let's turn to the epidemiology of type 1 and type 2 diabetes, which together affect a little over 2% of pregnancies in the United States. Let's see if we can switch to the next slide. There we go. Okay. So, here we see CDC data that shows approximately one in nine female individuals has type 1 or type 2 diabetes. And what's most concerning is that when we look at younger women between the ages of 0 and 19 years, about 35% of newly diagnosed cases of diabetes are occurring in female individuals of reproductive age. So, the panels you see right here are looking at CDC data and look at the rising prevalence of diabetes amongst U.S. youth from 2002 to 2015. And on the left, you see the incidence of type 1 diabetes has increased, but more so amongst minoritized populations, including Black, Hispanic, and Asian Pacific Islander individuals. And then, similarly, on the right, you see the rising incidence of type 2 diabetes amongst young people. And again, significant rise amongst minoritized populations, in particular, Native American, American Indian individuals. So now, let us examine what's going on during pregnancy with the rate of pre-gestational diabetes, and what's going on with regards to racial and ethnic and rural-urban disparities. So, on the left panel here, you can see data from the same paper in JAMA from a year ago that Dr. Carter presented. But here, we're looking at the rates of pre-gestational diabetes amongst nulliferous individuals. And what we see is that the rate has increased from about 7.3 to 9.0 per 1,000 live births from 2011 to 2019. And in particular, we see increasing rates amongst minoritized populations, namely, non-Hispanic Black, as well as Hispanic Latina individuals. And then, on the right, we see disparities in the rates of pre-gestational diabetes, again, using U.S. birth certificate data in the same time period, wherein individuals who live in rural areas have a higher risk of pre-gestational diabetes from 2011 to 2019. Of note, this rural urban disparity with increasing rates of diabetes amongst rural populations was worse for Hispanic individuals, as well as those who live in the South and West. So, these findings have implications when we're thinking about delivering equitable diabetes care in the United States for all communities, as well as when we're thinking about rural communities and maternity care deserts. As has been highlighted, individuals with pre-gestational diabetes have a two-fold, five-fold increased risk of adverse pregnancy outcomes and severe maternal morbidity. These include outcomes like preterm birth, cesarean delivery, large for gestational age, NICU admission, and its primary causes in this population, including neonatal hypoglycemia, and respiratory distress syndrome. But what about glycemic control, and what does that do for adverse pregnancy outcomes? So, what you can see here is the dose-response relationship on the left panel, which is, as glycemic control improves across pregnancy from early to late pregnancy, as measured by A1C, the risk of congenital anomalies decreases. And in the middle panel, you see that as glycemic control, again, improves over the course of pregnancy, the risk of large for gestational age also goes down. Now, on the right, we see as preconception or periconception hemoglobin A1C increases, the risk of severe maternal morbidity starts to increase. Hence why in clinical practice, many practitioners will check an A1C at least once per trimester. But now, what are the drivers of glycemic control? And how can this be achieved? So clearly, integrated diabetes and prenatal care and biomedical interventions are critical. But what about social determinants of health? Now, Dr. Carter just talked about the impact of individual social determinants of health and lived experiences on pregnancy outcomes with diabetes. But now here, let's take a broader look at neighborhood level social determinants of health at a structural or community level and think about its impact on glycemic control. Now, the panel on the left shows you the CDC Social Vulnerability Index, or SVI, mapped out across the United States where the darker colors represent increasing social deprivation and using this composite index and its subcomponents what we can see is that as social vulnerability increases glycemic control worsens or another way to think about it is that is that is that individuals with less SBI or less social deprivation were more likely to experience glycemic control now let's flip that on the right and here we look at to another index of social determinant at the neighborhood level and that is walkability and that is at the community level and what we see again here is that individuals who live with greater walkability again are more likely to achieve glycemic control and similarly we see that pattern with those living in food deserts so these findings highlight the importance of broader structural interventions potentially that need to be tested and what neighborhood level social determinants may be for glycemic control so now now that we've briefly discussed the epidemiology of pre-gestational diabetes let's turn towards pharmacotherapy and let's just take a quick detour back to gestational diabetes where Dr. Carter left us off and just talk about treatment there very quickly and then we're going to come back to pre-gestational diabetes and one point I do want to cover is the pharmacotherapy for gestational diabetes and the rising role of oral therapy for metformin so metformin is increasingly being used for the management of gestational diabetes and what you can see here on the top left panel is that using commercial claims data from the US from the 2016 to about 2018 metformin use dramatically increased or even doubled from about 15% to 30% during this time period gliburide use dramatically decreased and while insulin use remains the most prevalent with about 44% of pregnant individuals with GDM requiring pharmacotherapy getting it no doubt metformin use has increased what we do know about metformin is that it does prevent adverse pregnancy outcomes now while we don't have contemporary efficacy data from a generalizable US population what we do know from the Rowan studies conducted in Australia and New Zealand in the early 2000s is that metformin does prevent adverse pregnancy outcomes almost as well if not as well as insulin but there are persistent safety concerns so in the meta-analysis you see in the top two outcomes for neonatal hypoglycemia as well as large for gestational age which both suggest that metformin appears equivalent to insulin the concern for both patients and providers with metformin use has been the known placental transfer and what does that mean in terms of childhood safety the best meta-analyses we have to date which primarily again draws on the Rowan data from Australia and New Zealand suggest a slight increase in body mass index in children mean difference of about 440 grams at birth and then by mid childhood again a slight increase in BMI amongst those that were exposed to metformin in utero again this mean difference of 0.78 kilograms meter squared is statistically significant but to what extent is that clinically significant also requires further data now let's think about pharmacotherapy management in the setting of type 2 diabetes in the past few years there has been interest in considering what about adjunct metformin so insulin is the backbone for therapy however is there an additional role for metformin as a sensitizing agent on the left side you see data from the MITEI trial which was a prospective multi-center international randomized control trial conducted by Fugent team from 2011 to 2018 amongst 582 pregnant individuals with type 2 diabetes what they found was no significant difference in the primary composite neonatal outcome between the group and the primary composite outcome included multiple neonatal outcomes including pregnancy loss preterm birth birth injury RDS neonatal hypoglycemia and NICU admission using this data the authors concluded that we needed to really understand the implications of adjunct metformin use further but that metformin could be considered with shared decision-making among some patients of note metformin exposed neonates weighed less and had reduced adiposity and we're going to come back to that again and I think that parallels some of the data that we also see in the GDM population now on the right side you see data from the most recent mom pod trial which just was released this past year which was a RCT conducted in the United States completed in 2022 from 794 individuals pre-gestational diabetes again this patient population was different than the MITEI trial in which 51% of individuals identified as Latino or Hispanic and 29% as non-hispanic black of note almost all patients had used metformin in the past this study found no significant difference in the primary composite neonatal outcome again similar however the rate of the primary composite neonatal outcome here was much higher than MITEI again the primary difference here was that the primary outcome included large for gestational age which is different than MITEI which did not of note metformin exposed neonates were less likely to be born large for gestational age with these data the the investigators concluded there really was no efficacy or value in using metformin amongst individuals with type 2 diabetes and advised those that were using metformin to discontinue use and to only continue insulin monotherapy this is a follow-up data from the MITEI trial which suggests that there may be an association between metformin and an increased risk of SGA birth which was double amongst a metformin group versus placebo 12% versus 6 and more so amongst pregnant individuals who've had a morbidity no more namely hypertension and nephropathy so using these data the the authors concluded that perhaps metformin amongst individuals with type 2 diabetes and pregnancy should be used less so amongst those with a hypertensive disorder of pregnancy or those who may be at higher risk of having fetal growth restriction or a infant foreign SGA however of note at two years BMI and anthropometry were similar amongst those who were exposed to metformin. So now that we have discussed the epidemiology as well as pharmacotherapy updates for pre-gestational diabetes let's turn towards technology. Many of you are increasingly familiar with the use of continuous glucose monitoring particularly in the setting of type 1 diabetes and this is where we have the most evidence and increasingly in clinical practice many of you may have also seen rising use of CGM for type 2 diabetes as well as even GDM which are areas where we really don't have high quality data but coming back to type 1 the landmark study was the concept study that came out in the Lancet in 2017 which really examined the impact of CGM on glycemia and pregnancy outcomes. So this was a multi-center RCT of pregnant individuals as well as a smaller subset of female individuals of reproductive age who were desiring pregnancy with type 1 diabetes. Individuals were randomized and stratified by insulin delivery as well as baseline A1c to CGM versus self-monitoring blood glucose. The primary outcome for which the study was powered was actually A1c from randomization through 34 weeks and it included 325 or 215 pregnant individuals and then a 110 for planning pregnancy. The data below that I focus on today is amongst a pregnant subpopulation. So the authors did find a statistically significant albeit small difference in A1c with CGM use and that has again been seen in follow-up studies but most interestingly it of note for clinical practice for our patients with type 1 diabetes was the significant reduction in adverse neonatal outcomes with CGM use including large for gestational age, NICU admission, and neonatal hypoglycemia. Based on the concept data emerging guidelines suggest that CGM targets for pregnancy of 63 to 140. So some have asked whether we should replace A1c often that the ADA uses a 66.5% with time and range and that's something that we really need more data for to answer. Of note no RCTs have compared either different CGM metrics such as mean glucose versus time and range or different targets for CGM metrics like a mean glucose of 110, 120, or 130 in pregnancies complicated by diabetes. So I think really we are moving towards using time and range for type 1 people with type 1 diabetes and pregnancy but this is again something where we need more data not only in the type 1 population but certainly in the gestational and type 2 diabetes populations. So what about pumps? While data for CGM use is clear the value of pumps is less so and part of this has also been due to the rapid evolution of pump technologies. So historically several randomized trials showed no differences in glycemic control as well as adverse pregnancy outcomes with pump use. However newer data with newer pumps suggest possible improvements in glycemic control. In the concept study when investigators compared pump users with MDI what they did find were that MDI users were more likely to have good glycemic control and less likely to have gestational hypertension, neonatal hyper hypoglycemia, and NICU admissions compared to pump users which broadly fits with earlier data. So now turning to pumps I think the area where most of you probably have questions in contemporary clinical practice is with the use of hybrid closed-loop pump technology and while evidence for the use of these pumps during pregnancy is promising, data and guidance are still needed regarding use of these commercial systems. Unfortunately none of the hybrid closed-loop HCL systems that are currently available in the United States have glucose targets that are as aggressive as needed to meet pregnancy targets. None have pregnancy specific algorithms and none are approved for use during pregnancy. Now this is an area where I think we're going to see a lot more data in the coming years and there is data out of Europe in this space. Despite these limitations many patients and providers do decide to continue to use HCL systems in pregnancy. So what are some of the advantages and disadvantages of this approach? Advantages include automatic system with less need for intervention by patient and provider, there's less glycemic variability, potentially lower risk of hypoglycemia, higher time and range, better sleep, potential for better quality of life. Disadvantages are it's not efficiently licensed, glycemic targets are not necessarily appropriate for pregnancy, the lowest settings that you can set it to are 110 which is what we ask patients to do, insufficient data, insufficient flexibility to adapt to increasing insulin needs particularly as pregnancy progresses, insufficient possibilities for adaptation to physical activity as well as pregnancy. So if our patients do decide to use off-label HCL systems in therapy pregnancy, what are some of the options? And I highly highly recommend this review paper that just came out in Diabetes Technology and Therapeutics written by a group of clinicians that offer a set of useful guidelines of how we can help our patients use off-label HCL therapy. One is be flexible, continue to reassess whether automated HCL therapy is working or whether we should be going into manual mode, use the lowest glucose target of 110, actively adjust your carb ratios, actively adjust your correction factors, switch to more concentrated insulin formulation, consider even acting supplemental Lantus or Levomere as pregnancy continues, consider boluses and fake carbs. So I think there are many strategies that we can particularly use in the second and third trimester to help our patients use auto mode if they decide to do so. And then finally what about intrapartum diabetes management? This is food for thought in a recent RCT of 76 individuals with type 1 diabetes was an RCT that looked at intrapartum continuous sub-q insulin infusion versus intravenous insulin infusion or IV. The primary outcome was neonatal hypoglycemia and of note they found no difference in the primary outcome of neonatal hypoglycemia between two both groups. So I think this is really food for thought in that continuation of continuous sub-q insulin was comparable to IV insulin and I think this really opens another opportunity for shared decision-making particularly for our pregnant people with type 1 diabetes in terms of giving patients the option of either glycemic management strategy options intrapartum which perhaps in the past we weren't doing so. So with that thank you so much and we're going to turn over to Dr. Zuro. Thank you so so much. I'm hopeful that we're going to have a lot of time to talk. I can take over the slide. So I'm really going to focus on what about before and after pregnancy which for many of you who are in practice as endocrinologists I suspect is where you see the bulk of your patients. As you know pre-conception care really requires sort of managing all of the things right. Lifestyle management in an ideal world you're doing lifestyle management. We're looking at pharmacological management sort of optimizing medications stopping any toxic medications namely ACEs or ARBs which we can talk about in some more detail if we need to. But kind of optimizing all of that making sure that people have the supports that they need and making sure that their technology is optimized. The reality is is that that could really have a big impact and I'll just focus on one outcome congenital abnormalities. So this is one group that did a probabilistic model to estimate the cost. If we did universal pre-conception care for women with pre-gestational diabetes we'd be able to prevent more than 2,000 preterm births, a large number of birth defects and 500 or more perinatal deaths each year. The lifetime cost savings of this and this is nearly 10 years ago was estimated to be 5.5 billion dollars. Now there are also about 32,000 congenital heart defects per year in the United States that are identified in newborn babies. Again if we just focus on people with pre-gestational diabetes for those folks they have an odds ratio of just under four so there's much increased risk for having a baby with a congenital heart anomaly. The population attributable fraction of pre-gestational diabetes to the sort of national population of congenital heart defects is nearly 10%. If only half of them had good pre-pregnancy glycemic control we'd be preventing more than a thousand cases of congenital heart defects each year. So we would really have a substantial population impact. We know though unfortunately we don't do a great job. This is actually data from Ireland. So in Ireland where there's a regionalized healthcare system and everybody in theory has access to care they found that less than half of their patients with type 1 diabetes attended pre-pregnancy care and the average hemoglobin A1c prior to pregnancy was nearly 8%. Among their type 2s they had a lower A1c but many fewer of them attended pre-pregnancy care not even 30%. And by a year postpartum there had been no improvement in measures of diabetes control despite having gotten really intensive care during their pregnancies and one in five were completely lost to follow-up. So this is again in a place where there's a national healthcare system that in theory has able to fully care for their population. What about the United States, nearly half of the births are financed by Medicaid. As you may or may not know, Medicaid is expanded in many states, but not all. And pregnancy care is only federally mandated to continue for 60 days after pregnancy. So, we know that we have a substantial portion of patients who just aren't even able to access care before and after pregnancy. Public insurance is associated with a lack of preconception care. Our group looked in a state, so Massachusetts has really had nearly universal healthcare coverage since 2006. And so, we looked at our population in a multidisciplinary clinic, and that, again, in theory, should have had nearly universal access to care. And we found that public insurance was associated with not getting a preconception consult and having no primary care provider. So, despite being, again, in a state where, in theory, they should have been able to access care, most of our patients who were covered by Medicaid weren't able to get to care before pregnancy, and it's even worse in most areas of the country. In reproductive age U.S. women in general, we know that there's a huge proportion of them that have undiagnosed diabetes. This is the most recent estimate, which is actually, unfortunately, substantially increased from what I used to quote. I had to finally update this slide. Data from NHANES estimates that about 830,000 people have uncontrolled diabetes. So, again, these are women of reproductive age who have undiagnosed and uncontrolled diabetes. Risk factors for undiagnosed diabetes, again, lack of insurance. So, if you don't have care, you're much less likely to have the diagnosis in the first place. Poverty, obviously, associated with undiagnosed diabetes, and then, unfortunately, in many places in the country, the level of poverty you have to achieve to be able to qualify for Medicaid is really fairly substantial. And so, many people are living functionally. They're not really, you know, making a living wage, but still don't have health care. Obesity is also associated with undiagnosed diabetes, and as is Hispanic ethnicity, which does track with lack of access to health care and lack of access to insurance. So, what is the low-hanging fruit for us? I think the easiest target is let's find the highest risk groups and make sure that we're diagnosing them. Diagnosis of diabetes after gestational diabetes is the low-hanging fruit. Unfortunately, in usual care, the sort of mean of reported rates of screening is about 30 to 40%. That's, again, in that first-year postpartum. A recent paper looked at commercially-insured women only, and only a third of those who had gestational diabetes and had a primary care doc receives the recommended blood glucose testing by 12 weeks postpartum. So, this is, in theory, the best-case scenario. Commercial insurance, you have a primary care provider, and, again, we know what to do, but it's not happening in the real world. In an ideal world, this is what we should be doing, you know, gestational diabetes, a fasting plasma glucose, or a 75-gram, two-hour OGTT at 6 to 12 weeks postpartum. With identification, really, of that group that has impaired fasting glucose or impaired glucose tolerance, those are far and away many more common than those who have overt diabetes at that 6 to 12-week time period. We do have a real opportunity for diabetes prevention if we do this right. So, I'll just leave us with, I'm going to try to give us some time to talk as a panel. You know, when we think about what we can do as individuals, we're talking about counseling and education. We have clinical interventions, but really, part of improving diabetes care before and after pregnancy is going to have to include addressing national healthcare policy. So, I always like to throw this in when we talk about diabetes, because I don't think we can talk about it without acknowledging that people need to be able to access healthcare to have their pregnancy optimized. Finally, I'm going to hand off. We're going to do a couple of cases, and then we ask Dr. Carter and Dr. Venkatesh to come back when they have a moment. And we have a case. So, here's the first one. Thirty-six-year-old, gravity-three para-2 with a history of gestational diabetes who had only needed diet to control it in her last pregnancy. So, she asks you, what kind of testing should I have for diabetes? So, I think if I understood Dr. Carter's take-home point, we should do something. There are a bunch of different ways of doing it, but if you had your druthers, you'd be doing screening with a 75-gram in the first trimester? Well, I will, I will, you're asking me, right? So, my, my pragmatic answer is that in my very high-risk patient population who has many social barriers, I actually tend to start with an A1C because I can just add it to their initial prenatal labs, and I know that I have it. So, that's actually usually my starting point. So, if you knew that she had other risk factors, like she had a baby who was large for gestational age and macrosomic, and she has a first-degree relative with a history of type 2 diabetes or at least gestational diabetes, would that affect your decision in terms of a screening test, or would you still stick to the pragmatic sort of A1C? I tend to be pragmatic with my patient population because what I find is when I order, like, you know, if somebody has to come in fasting to get a test, it often doesn't get done. So, at least I have a sense of where I am, you know, even if it's imperfect. How about you, Dr. Venkatesh? Do you have a preferred method for screening the high-risk folks in the first-trial? I agree with Dr. Carter in the testing approach. That said, you know, with shared decision-making, what I sometimes do is I do the A1C, and then I tell the patient why, you know, I want that, you know, fasting test, and sometimes, you know, we'll get both. And to add to that, I think, you know, there are some state programs, including California, for example, where they have started including A1Cs as part of routine prenatal lab battery early in pregnancy for all Medicaid-enrolled patients. So, I think there is some regional variation there in terms of GDM screening, including with A1C. Yeah. And full disclosure, we have shared routes, so we often got, we probably all got trained to do that. So, I, too, am an A1C fan in the first trimester, just to find the folks that are really have the most overt diabetes. But sometimes, you know, if you have somebody who's really interested in knowing whether or not they have impaired glucose tolerance at this point, I would let them have a 75 gram if they were asking for it. Totally agree. Okay. There are few and far between who ask for the ODT. So, case two, her next pregnancy. So, you followed the guidelines and tested her for diabetes at 12 weeks postpartum and identified her type 2 diabetes. Her most recent A1C prior to pregnancy is 7.1%. So, how about medication? Dr. Venkatesh, I'm going to see if I got the take-home message from you, which was that depends on how much insulin she needs, maybe I could sneak the metformin in there. As long as she doesn't have, you know, nephropathy or retinopathy that's out of control. But I might want to do some growth scans along the way because I'm a high-risk obstetrician. I'm going to make sure that that baby isn't too growth-restricted. Does that sound right? That's right. I think, you know, I think the story with metformin for pre-gestational diabetes continues to evolve, and people can take the data, even though it's negative trial data, and interpret it differently. But I do think we are seeing an emerging picture where metformin does seem to be associated in certain instances with fetal growth restriction. So, I think in subpopulations of patients, perhaps even those with chronic hypertension, strong history of hypertensive disorders of pregnancy or FGR, use metformin with caution. Okay. Yeah. And mostly, we're all using insulin, I think, for the patient with known type 2 diabetes. Right. And again, our recommendation would be, it would be adjunctive metformin, right? So really, you know, insulin is our backbone, and the question of whether or not to, and I think for many of these patients, it's a matter of they're already on metformin, and many times patients have strong preferences about whether they want to continue it or not. Now, here's what I think, my being the policy advocacy person, my patient doesn't have enough money to test her blood sugar four times daily, or four to six times daily, because she's getting her lows in the middle of the night, because she's on 120 units of MDH, right? So, what do you think about a CGM? Yeah, and I think there are... We don't have data, right? That's the take home? We don't have data. Right. We don't necessarily have data for type 2 and GDM. And I will say some of the observational data we're seeing doesn't actually necessarily suggest that CGM use with type 2 is actually associated with improved glucose control or a decreased risk of APOs. So it's not necessarily mirroring what we see with type 1. That said, it's from observational cohorts, but I think that's still food for thought. That said, I think, you know, we are seeing rapid uptake of CGM in these populations, and that's going to continue to evolve very quickly. And I will say in Ohio and in about another 10 states, Medicaid programs are offering CGMs to type 2s, as well as individuals with gestational diabetes. So we are seeing rapid uptake of these technologies amongst those patients, even before they seek prenatal care or a diabetes consultation with MFM. So I think that's just the rapidly evolving technology landscape and how these technologies sometimes can rapidly evolve in a U.S. marketplace before we even have data. Well, and I will also add that for our patients who are on insulin, that Medicaid is paying for CGMs for them now. So most of them actually are on CGMs. Right. And that's what we're seeing in Ohio. And I think that really varies based on the geography, as well as your kind of payer mix locally, but yeah. That's great. So for me, the reason I put which one is I would say that most, I can count on one hand, the number of folks with a CGM who have come in with like a Dexcom, the vast majority have come in with a freestyle Libre. Our experience has been that it's less reliable. But I wondered if either of you have, I haven't seen any data on that. I wanted to throw it out because I suspect that the audience may have experienced this. I tend to say let's depend on at least a little bit of finger stick glucose testing, even if you have a Libre. I don't think we have data on that, but I agree in clinical practice, that's exactly what we're seeing. Also for patients and providers, in terms of switching to pregnancy specific time and range and metrics, much easier with the Dexcom versus the Libre. You can do it, but it does take a little more tweaking. And I feel like we're not even making the decision. It's dependent on what the payer is paying for or willing to pay for. Right. All right. So I know that we have about 10 minutes left. I'm going to try to wrap this up with our last case. A 27-year-old gravity zero in your practice recently decided to have her IUD removed. Her A1C is 6.2% and she has a hybrid closed loop system. Do you change it? I think Dr. Venkatesh, if I heard you right, no. And maybe I'd even let her use it as a delivery. I think that's really shared decision making. And it's talking to patients about the fact that this is a data-free zone. All hybrid closed loop systems that are available in the US right now, the best you can set it to is 110. The algorithm is not pregnancy specific. And there's really nothing under review by the FDA now that might change in a year or two. Certainly in Europe, the landscape is different where they do have pregnancy specific closed loop algorithms in place. So I think it's just it's dependent on having that honest conversation with patients and then saying, well, what happens by the late second to third trimester where we can get auto mode to work, but then what happens if it starts not working? And I think that's where that recent review paper is very helpful in terms of providing some clinical benchmarks and guidance to clinicians in terms of what are some strategies that one can use. But I think the take home here is to be flexible to work with the patient and to kind of constantly reevaluate whether auto mode is working at every prenatal visit. That's great. The last one, this is really more of a grenade to throw into the audience since we didn't talk about it at all. But this comes from real life experience with me in my practice. I have now a couple of patients who have type one diabetes, but also have obesity and are on the GLP-1. And they're wondering when prior to pregnancy they should stop. And so I'll throw in that we have no data yet on GLP-1. We have a pregnancy registry that I'm aware of, but I haven't seen anything published, some theoretical risk, what the label says or the package inserts say stop for three months prior to pregnancy. So at this point in time, I would take folks off. But with the caveat that I would see them frequently or at least check in with them frequently because you're going to destabilize their glycemic control rate as they're about to get pregnant. Any questions in the panel? Okay. Number one, is it helpful to check A1C during pregnancy? I've done it both ways. I don't know. I'm going to open this up to the panel. I don't think we have a right or a wrong answer. I can tell you that practicing in the same city at two different institutions, we were a hard no at one and we're a hard yes at the other. So we do it monthly here. Our current practice is we do it monthly. And I think patients like it with all of the caveats that your A1C is not a reliable metric in pregnancy. And so we know that A1C drops about a percentage point. And so we have to encourage patients to understand their numbers, that an A1C of 6.5 during pregnancy is not the same as an A1C of 6.5 before pregnancy. And I agree with you. I tend to use it for like that early screen. And then for patients with pre-existing diabetes, I use it at baseline so I can counsel based on anomalies in terms of where their control is. And after that, I tend to use it if people just are not bringing data back. Like if I have no idea where they're living or I just need some more like hard numbers, it's the other time I will use it. Yeah. Agreed. I think early in pregnancy, super helpful for risk stratification and thinking about severity of diabetes, risk of adverse pregnancy outcomes. And I think it also helps patients because it's a number they know if they're thinking about their goal. So if they're starting pregnancy at like eight or nine, and then they're able to get to that six by the third trimester, I think that's, you know, it's helpful in terms of guiding patient care. But with all those caveats that even a 6.0 sometimes is not good enough when you look at the actual numbers. Absolutely. All right. So the GLP-1 question showed up in the chat as we thought it would. And somebody with type 2 diabetes who wants to get pregnant, how long do you tell them to stop their GLP-1 or their SGLT-2 inhibitor? The GLP-1s, I'm still saying three months. SGLT-2s, I'm a little more lenient because there are some case reports that there are folks using them during pregnancy. And so I feel a little more comfortable because there's a tiny bit smidge of data. I don't know if the two of you have an alternative thought. I think a related question to this is going to be increasingly even amongst our gestational diabetes population when we think about postpartum cardiometabolic health. Many of these patients are particularly interested in going back to these agents, whether it's for glycemic control in the pre-gestational group or diabetes, obesity prevention in the GDM population. So we really need more data with breastfeeding. And right now, we really don't have that. That said, these molecules are highly protein bound. So they shouldn't transfer that much in breast molecules theoretically. But we don't really have data at this point to inform those conversations. Absolutely. OK. I'm just going through the questions here just to see if there's things we haven't covered. You know, we didn't talk about sulfonylureas really at all. There is a question about the role of sulfonylureas in diabetes control. And I would say I do not use them at all because I feel like the risk of hypoglycemia is real in people who need just the titus medication. And the risk of poor control is real in everybody else. So that's my take on sulfonylureas. And if we look at the same data, like, glyburide use dramatically decreased, even the setting of GDM over the past five years, you know, guidelines essentially advised against its use, both in terms of the hypoglycemia risk. And then finally, there was a non-inferiority trial that came out of France a few years ago, which was unable to prove non-inferiority of glyburide. And after that, use fell even further once SMFM, ACOG, and ADA advised against using it. Yeah. And I do not use it. I saw a question in the chat about metformin. I do use metformin after careful counseling with patients. And for reasons for why we're going to do it. Yes. All right. I think we are rapidly reaching the end of our talk here. So I'm going to go ahead and wrap up. I want to thank everyone for coming. Again, encourage you to do your evaluations and claim your CME. And I believe that is what we have. Thank you so much, everybody. Thank you to Dr. Venkatesh. Thank you to Dr. Venkatesh and Dr. Carter for joining me today. Thank you for having us.

diabetes

pregnancy

gestational diabetes

diagnosis

management

screening methods

diabetes technology

preconception care

underserved populations