Speaker 1:

Welcome to AACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com/podcasts. And now, let's meet the endocrine experts who will be talking with us today.

Vin Tangpricha, MD, PhD:

Hello and welcome to this edition of the AACE Podcasts. My name is Vin Tangpricha. I'm the host of today's podcast. I also serve as the Editor in Chief of Endocrine Practice, the official journal of AACE. Today we're lucky to have our guest speaker Dr. Cecilia Low Wang, who will be talking about her article, entitled Safety and Efficacy of Insulins and Critically Ill Patients Receiving Continuous Enteral Nutrition. Thanks Dr. Low Wang for joining us today. Could you introduce yourself to the audience and tell us what you do?

Cecilia C. Low Wang, MD, FACE, FACP:

Sure. Thank you so much, Vin. My name is Cecilia Low Wang and I'm very happy to be here. I'm Professor of Medicine at the University of Colorado in Aurora, Colorado, and I am the medical director for the glucose management team for our hospital, which is the University of Colorado Hospital Metro.

Vin Tangpricha, MD, PhD:

Great, excellent. Well, thanks for joining today's podcast. Your paper covers a very important topic, especially in inpatient diabetes care. Before we jump into your paper, can we talk a little bit about how to manage insulin, especially in people on tube feeds? I feel like that is very challenging for all of us, especially with timing of the insulin and trying to correct the hyperglycemia without causing hypoglycemia. Could you give us some quick pointers on what are the key treatment points and what are the pitfalls?

Cecilia C. Low Wang, MD, FACE, FACP:

Yeah, I think you hit the nail on the head. It can be challenging. We know that almost half of people with or without diabetes can develop hyperglycemia when they are placed on enteral nutrition, which is a very non-physiologic way of eating, especially when it's continuous. And there are a number of things that can cause interruptions in the tube feeding. So, some of these are planned. So, for example, when tube feeding is stopped in order to prepare for procedures the next day or to administer medications, or sometimes placement needs to be rechecked, etc. But then, there are lots of unplanned interruptions. So, for example, when people develop symptoms with their tube feeding or the tube is dislodged, there are different reasons for unplanned interruptions for tube feeding. And I think the difficulty is that we really don't have a standard way of delivering insulin. So, we don't have standard insulin regimens for patients receiving continuous tube feeds.

So, one of the ways that we could manage this is with basal bolus regimens, and the problem is that if the basal insulin is adjusted for continuous tube feeds to cover the calories being received while people are receiving the tube feeds, then when there's planned and unplanned interruptions, patients can become quite hypoglycemic. So, that's one issue. The other is that patients can become very hyperglycemic. And then also, many patients receiving continuous tube feeds are in the ICU, so they're critically ill. They may be receiving high-dose glucocorticoids, they may be receiving pressors, etc. So, other reasons for becoming very hyperglycemic. And so, being able to kind of balance those two issues can be an issue.

And then, I think the other problem is that in order to manage potential hypoglycemia because of longer-acting insulins being received when patients are on continuous tube feeds, there's often an as-needed dextrose infusion order, but because those are as-needed, it may or may not be noticed when tube feeds are interrupted. So, it may or may not be started at the right time.

Vin Tangpricha, MD, PhD:

I know we're talking about continuous enteral nutrition, but when I'm on the endocrine service, I hate the 24-hour tube feed for use in patients. Is there any role for bolus feeding or overnight feedings? I always try to convince the nutrition service to consider that because that's way much more manageable than 24-hour tube feeding.

Cecilia C. Low Wang, MD, FACE, FACP:

That's interesting that you say that because I think in some sense, continuous tube feeding may be easier to manage if patients aren't also taking PO or trying to eat in addition to the tube feed. Because the tube feeding is being received continuously, we can try to manage the insulin in a fairly stable way. It's when there's a combination of tube feeding plus taking PO intake that it can be more difficult. But I would say that bolus tube feeding is probably one of the more physiologic ways of delivering tube feeding, and we can use carb ratios or fixed doses of insulin to manage bolus tube feeding.

Cyclic is one of the most difficult I think, because patients are being fed usually overnight so that they can try to eat during the day. And of course, that isn't physiologic. We don't normally eat overnight and it can cause very, very severe hyperglycemia. And trying to manage types of insulin, oftentimes, we might be using intermediate acting at the start of cyclic tube feeding, and oftentimes we have to give a second dose. And then, how do you divide those doses up and then give the right proportions to manage? Sometimes late night or early morning hyperglycemia can be a challenge. So, they all have different challenges.

Vin Tangpricha, MD, PhD:

I guess, I'm thinking more of the outpatient person because I follow people with cystic fibrosis related diabetes and sometimes they're recommended to have overnight tube feeds. And so, I'm increasing the intermediate insulin overnight so they can eat during the day.

Cecilia C. Low Wang, MD, FACE, FACP:

Absolutely. And I'm sorry to interrupt. I think that's such a different situation because trying to translate what we do in the hospital to what's done in the outpatient setting is very different. We can give insulin every four hours overnight in the hospital, and that's really not something that we would want someone to be doing outside the hospital. It's very disruptive.

Vin Tangpricha, MD, PhD:

But it sounds like bolus tube feeding, as long as there's not large residual volumes from the tube feed might be a good strategy. More physiologic, maybe?

Cecilia C. Low Wang, MD, FACE, FACP:

Yes. I think that that's more physiologic, and I think that what you said though is the balance, is that some patients just can't tolerate larger volumes in that short amount of time. So, that's the difficulty.

Vin Tangpricha, MD, PhD:

Okay, great. Well, let's jump into your paper because I think it's very interesting. It's studies three different ways of giving insulin in patients who are on continuous tube feeds in hospital. Maybe you can help us walk us through the study. Who was in the study and what were the interventions that you studied?

Cecilia C. Low Wang, MD, FACE, FACP:

Yeah. So, what we were interested in doing was to study how we manage our patients on continuous tube feeding in the hospital. And we tried to focus the question to patients who are critically ill, receiving continuous tube feeds, with or without diabetes. And we looked at both the efficacy, what we called efficacy, which was really the point of care glucose is in the target range of 140 to 180 milligrams per deciliter, balanced with hypoglycemia or severe hyperglycemia. And our standard practice in our hospital is to use one of three regimens and either 70/30 insulin Q-8 hours, with correctional rapid acting insulin every four, or what we called long-acting insulin, which was really more of a basal bolus regimen.

So, long-acting insulin with either glargine or detemir VID, in addition to rapid acting insulin correctionally delivered every four hours. And then, the third regimen was just rapid acting insulin only every four hours. And the key difference here is that at that time, in this period of time that we were looking at, we hadn't started using nutritional doses of the rapid acting insulin. This is something we started doing more frequently in the past year, but this particular calendar year that we studied, we hadn't started that practice yet.

Vin Tangpricha, MD, PhD:

Okay. So, before we move on the 70/30 insulin, does that apply to all 70/30s or is that a particular brand of 70/30, or it doesn't matter?

Cecilia C. Low Wang, MD, FACE, FACP:

No, it doesn't matter. So, we were using human insulin and pH 70/30, so it wasn't the analog pre-mixes.

Vin Tangpricha, MD, PhD:

And how does a provider at your hospital decide among these three? Is it a provider preference or are there factors that go into which one of these that people go on?

Cecilia C. Low Wang, MD, FACE, FACP:

So, we do have a tube feeding order set. We had one at the time of the study. And so, the tube feeding order set includes various options. So, one is the rapid acting insulin only. One is 70/30 Q-8 hours, and one is the basal bolus. And so, preferentially, if providers were to use the order set, they would have that option of 70/30 Q-8 hours. But in reality, the main service that would use 70/30 Q-8 hours was the specialized glucose management team.

Vin Tangpricha, MD, PhD:

So, the basal bolus, the only difference between the rapid every four hours versus the basal bolus is basically the basal, right? It's the same, basically.

Cecilia C. Low Wang, MD, FACE, FACP:

Exactly. Yeah. So, with the basal bolus, what we call long acting in the paper, people would have the addition of basal insulin.

Vin Tangpricha, MD, PhD:

Okay. And how are adjustments made? I mean, so let's say someone's glucose is in the 200s, is there an adjustment to the regimen or is this the same thing as continuous throughout?

Cecilia C. Low Wang, MD, FACE, FACP:

This was up to provider practice, and so I think that just as in many hospital settings across the country as I understand it, this can vary quite a bit. And so, when patients become hypoglycemic, I think there are changes made to reduce the overall amount of insulin that's delivered or sometimes insulin is held. And then, when there's hyperglycemia, it may or may not be addressed for a few days. And so, when patients are being managed by the glucose management team, we would often make changes sometimes up to two times a day or more often based on how blood sugars are doing. But we would make changes at least once a day.

Vin Tangpricha, MD, PhD:

Okay. I mean, it would make sense that a change would have to happen every day based on what happened in the past 24 hours, right?

Cecilia C. Low Wang, MD, FACE, FACP:

I think that it would make sense, and we strongly encourage our clinical teams and our trainees to review glucose daily and make these changes daily. But I think that in the long list of different problems that patients are facing and that clinical teams are trying to manage, sometimes glucose falls to the bottom. So, it may not be something that's done every day unless a glucose is extremely severely low or high. So, sometimes it's just missed.

Vin Tangpricha, MD, PhD:

Okay. So, let's skip back to your study. So, it sounds like the patients were divided into three groups mostly by provider preference. Tell us what you found.

Cecilia C. Low Wang, MD, FACE, FACP:

Yeah. So, we did the analysis in a number of different ways. So, again, this was a calendar year 2019. We had identified 475 patients that met our criteria of receiving continuous tube feeding and subcutaneous insulin. So, we excluded patients who were receiving IV insulin or were not receiving continuous tube feeds. And we ended up with about two-thirds of the patients with diabetes and about a third without diabetes. And so, that ended up being about 491 admissions with continuous tube feeds and a total of almost 2,400 days of tube feeding.

And about 41% of those patients were on medical services, about 59% were on surgical services, and about a third of patients were receiving glucocorticoids. And most of the patients had type 2 diabetes. There were very few with type 1 or other diabetes. And what we found is that both long acting and intermediate acting regimens were efficacious and safe. So, in other words, higher time and range, so glucose is between 70 and 180, and less time in hypoglycemia or hyperglycemia compared with those on the rapid acting regimen.

Vin Tangpricha, MD, PhD:

I guess, that's not so surprising because the rapid acting regimen isn't providing any sort of basal at all.

Cecilia C. Low Wang, MD, FACE, FACP:

Absolutely. And I think that this is a reminder to people that, because we see this surprisingly often when patients are started on tube feeding and they don't receive kind of proactively insulin to cover their nutritional needs. And so, we're still seeing this fairly often. So, I think it's a reminder that we do need to be thinking about nutritional needs when we're taking care of our patients on enteral nutrition.

Vin Tangpricha, MD, PhD:

Were these people on enteral nutrition also eating PO?

Cecilia C. Low Wang, MD, FACE, FACP:

So, that wasn't defined. So, that wasn't something that we were able to identify in our search.

Vin Tangpricha, MD, PhD:

Okay. I was just wondering maybe a certain number of them were eating and they were having breakthrough hyperglycemia just because the Q-4 hour regular is definitely not going to be able to handle any additional calories.

Cecilia C. Low Wang, MD, FACE, FACP:

Absolutely, and you bring up an interesting point. So, many of the people who were eating as well as receiving continuous tube feeding, generally they weren't eating very much because this was during kind of that calorie count period, trying to figure out whether or not it's appropriate to stop the continuous tube feeding because they're taking enough PO. But many patients on continuous tube feeding are not eating, so they're NPO and receiving the tube feeding for a reason. It's because they either have issues with swallowing or they're intubated, etc. So, I would say, it's probably a low percentage of patients who are also eating while they're on the continuous tube feeding or they're taking in very little PO.

Vin Tangpricha, MD, PhD:

Okay. It is somewhat surprising or maybe not, the 70/30 every eight hours was the same as basal bolus. And I guess, I'm just trying to understand. I mean, I guess in the 70/30, you're sort of having the rapid acting insulin in there and you're getting a basal as well. So, I guess maybe it's not so surprising that they were relatively equal. What do you think?

Cecilia C. Low Wang, MD, FACE, FACP:

That was surprising to me. So, we had published this very small retrospective study a few years ago looking at 70/30 given two or three times a day compared to basal bolus. And in that very small group of 22 patients, we found that there was less hypoglycemia with 70/30 Q-8 hours compared to Q-12 hours versus the basal bolus, and also improvement in less hyperglycemia as well. So, that's kind of why our practice changed over to 70/30 Q-8. And so, the idea was that patients were having some degree of glycemic control because of that regular insulin acting sooner, and then the NPH in that 70/30 giving the basal coverage. But because it was being delivered Q-8 hours, that total dose for each dose was lower than kind of the long-acting dose. And so, the risk for hypoglycemia was thought to be lower.

Vin Tangpricha, MD, PhD:

Well, I wonder if in the basal bolus, instead of every four hours, if you did the regular every six or eight hours, you might have better results?

Cecilia C. Low Wang, MD, FACE, FACP:

Well, so the basal bolus was a combination of either laryngine or detemir twice a day, plus rapid acting lispro insulin Q-4. And so, of course other strategies that are used by different clinical teams across the country include NPH Q-8, NPH Q-6. There's actually a publication of NPH used Q-4, and then some teams use regular insulin Q-6. I mean, there's so many different regimens out there, and then of course lispro Q-4 to cover both nutritional and correctional needs.

Vin Tangpricha, MD, PhD:

So, are you saying there is no international standard at all?

Cecilia C. Low Wang, MD, FACE, FACP:

No, and if you read the consensus statements and kind of the clinical practice guidelines by the professional societies on in-patient management of glycemia, there's really no strong recommendation either way. So, they mention use of basal bolus or intermediate acting regimens, and there's no way of determining initial doses, etc.

Vin Tangpricha, MD, PhD:

Makes me feel a little bit better. But it sounds like you need some sort of basal, however you want to do that, either very long acting or intermediate acting throughout the day, plus a more rapid acting. But there isn't a standard how to do that, right?

Cecilia C. Low Wang, MD, FACE, FACP:

Well, one other point I wanted to make is that we saw big differences between patients with and without diabetes. And so, of course this is not surprising in that patients without diabetes developing stress hyperglycemia from the tube feeding may look very different from those with type 2 diabetes receiving tube feeding. And so, the average glucose of those without diabetes was much better than those with type 2 diabetes. And we didn't see differences in hypoglycemia, but the average glycemia over these tube feeding days was much improved in those without diabetes.

And so, I think that in terms of whether or not a patient needs to have basal insulin, I would argue that the patients without diabetes may not need basal insulin, and that might be a reason that intermediate acting or the shorter acting regimens might work better. And one thing we didn't test, and we couldn't test this because it wasn't practice at the time, was rapid acting only, covering both nutritional and correctional needs.

Vin Tangpricha, MD, PhD:

That makes sense. I mean, I kind of like the 70/30 every eight hours. That seems to be not too long of insulin, but enough to cover the carb load. I don't know.

Cecilia C. Low Wang, MD, FACE, FACP:

Yeah, that's kind of how we feel about it. So, the reason that we decided to do this study was that all we had to justify that 70/30 Q-8 hour regimen was that small retrospective study. So, we wanted to take a more global look to see how patients were doing on that. And I think that what this study kind of reassured us, although of course there are many limitations to the study, is that 70/30 is no worse and maybe better than basal bolus. And so, I think there's still a lot more work to do, but it was reassuring.

Vin Tangpricha, MD, PhD:

Are you aware of any large head-to-head studies looking at this in detail?

Cecilia C. Low Wang, MD, FACE, FACP:

I am not aware of any, and I think that this would be a really good area for future study.

Vin Tangpricha, MD, PhD:

Yeah.

Cecilia C. Low Wang, MD, FACE, FACP:

For a randomized trial.

Vin Tangpricha, MD, PhD:

Yep, I agree. Can you give us some key two or three takeaways from your studies before you leave us?

Cecilia C. Low Wang, MD, FACE, FACP:

Yeah. I think that one is that there are a number of different options to adequately treat hyperglycemia associated with continuous enteral nutrition, and some of the different strategies are quite effective. So, using intermediate acting insulin regimens, for example, 70/30 Q-8 hours with correction every four, or using long acting in addition to correctional insulin every four, both are effective. And I think one of the key points is to assess the regimens, assess the glucose control daily, and sometimes even more often than that, to keep our patients within the goal ranges.

Vin Tangpricha, MD, PhD:

I think these are very important points and it shows that, I guess, we need to learn more about this. And I think the key is to look at the glucose's every day and try to make our best adjustments. And so, really thank you for joining us today, and for people who want to read more, this is in the April 2024 Endocrine Practice. It's online, and really appreciate you doing this research. And I hope you can continue to give us some more information about this.

Cecilia C. Low Wang, MD, FACE, FACP:

Thank you so much, Vin. I really enjoyed this conversation.

Vin Tangpricha, MD, PhD:

Thanks so much for joining.

Speaker 1:

Thanks for listening to another great AACE Podcast. Join us for another episode at aace.com/podcasts, and help us in our mission to elevate clinical endocrinology. Together, we are AACE.