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Key thought leaders in endocrinology review different signs and symptoms of hypoglycemia across vulnerable patient populations and discuss factors that may impact the pharmacologic management of blood glucose levels.
Peter Salgo, MD: Which patients are most vulnerable to hypoglycemia: type 1 or type 2 [diabetes]? Who are these folks?
Davida Kruger, MSN, APN-BC, BC-ADM: It’s a misconception that only individuals who have type 1 diabetes are at risk of hypoglycemia because we do know that individuals with type 1 and type 2 have hypoglycemia. It has more to do with the therapies than it may seem. For all patients who are taking insulin, we know that they are at risk for hypoglycemia. We are still, unfortunately, using sulfonylureas to treat type 2 diabetes. They cause horrible hypoglycemia. Different types of therapies we use will also cause it. There’s also a thought that if your A1C [glycated hemoglobin] is really well controlled, you’re at greater risk for hypoglycemia. Well, if you look at the clinical research that has been published, there are as many people in the higher-A1C range who have hypoglycemia as there are in the low range. For the low range, obviously your blood sugars are always 70 to 120 mg/dL, you are more physically active, and you’re going to go low. That doesn’t mean those individuals who have high blood sugars will not have this occur—they treat high blood sugars; they may tank as well. We can’t say this based on an A1C; that’s not the best predictor of who will have hypoglycemia.
The other thing is physical activity. If a patient is more physically active than they usually are—we saw a lot of that during the pandemic when people were home from work; they would walk just to have something to do. I had people who would walk 2, 5, or 10 miles a day. They weren’t used to walking that distance, and the therapies we were giving them weren’t based on them doing those types of activities. Some people were even swimming. We have to watch people who are swimming. We must watch people who are on insulin. We have to watch people who have high A1Cs, low A1Cs—all kinds of ranges. We also have to watch for poor renal function and know the duration of their history of diabetes. The reason behind knowing the duration of their diabetes is that patients at the beginning of their diabetes typically have symptoms of hypoglycemia.
Some of the more common symptoms include getting shaky or sweaty. Later on, patients may have an adrenergic response where they cannot think as well. I always say that people have their own symptoms. It’s like an aura with a migraine. People get to know, and their family members get to know, what that person’s symptoms are. Maybe they talk too fast. There are a lot of reasons and things associated with hypoglycemia that we really need to talk to patients about, and there are symptoms they need to be aware of.
Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM: Often, we think only certain people are at risk. We really should be having this discussion with everybody. I will anchor the point: We did a study in our practice [Touro University California College of Osteopathic Medicine] in which we took all comers and put them on CGMs [continuous glucose monitors] that were blinded, and we found that when people did their normal activities, half of our patients dropped low during that week. It was incredibly shocking to us, and we thought it would have been much lower. This is really an underappreciated phenomenon. We absolutely know that the risk is higher with those taking insulin and sulfonylureas, but we really need to recognize that there are many nonmedication factors like alcohol intake and physical activity that also can contribute. Often we encourage people to be more active. When we view that, we may have to adjust therapies.
Elaine Apperson, MD: I would add to the symptoms part that we tend to divide them in 2 categories. There’s the bodily response, or the way you would feel if you had skipped or you’ve gone out to be active. You recognize those signs, like being shaky or your heart rate going up. You might start sweating a little more. You might feel very unsteady on your feet. There are also brain-based responses where your thinking is not where it should be. You might become a little disoriented. To go back to what Anne said about hypoglycemia unawareness, the way I explain that to my patients is to think of the scariest movie you’ve ever watched. Then think about the 10th time you watched that. Do you become as scared? Does your heart rate go up as fast as it did the first time you watched it? Of course not. Your body has seen that before. Your brain has seen that before. We know that, after repeated episodes of hypoglycemia, your body has seen that before. It’s not going to respond the same way. It’s not going to give you the signals.
When my patients come in and I asked them if they had any lows, they may say, “No,” but they’re not checking their blood sugar. The next question I ask them is, “How do you know if you haven’t had any lows?” They may say, “I should be able to feel them.” I will say, “No, it’s not the case that you necessarily feel your lows. You have had diabetes for 10 years, and if we were to put you on a CGM, or continuous glucose monitor, we probably would discover that you’ve had some lows because your A1C has dropped a lot. All the numbers that I see on your meter are high, so somewhere, somehow, you are probably having some lows, and that scares me.”
Peter Salgo, MD: What’s more associated with hypoglycemia: insulin or sulfonylureas?
Elaine Apperson, MD: Well, it depends on if you have type 1 or type 2. If you are a type 1 diabetic, you’re probably not taking sulfonylureas.
Peter Salgo, MD: Right.
Elaine Apperson, MD: I’m a pediatric endocrinologist, so for me it’s going to be the insulin.
Davida Kruger, MSN, APN-BC, BC-ADM: I don’t think you can define it that way because they both cause hypoglycemia. It has to do with doses, activity, if you missed a meal. It has to do with so many things that I don’t think you can. We have wonderful new medications that don’t cause hypoglycemia, and we’re really trying to move patients to those as opposed to using sulfonylureas or insulin when it’s appropriate. Most patients will need insulin in their career of diabetes, but I don’t think you can say 1 sulfonylurea or insulin is better or worse. I would also say that sometimes, when blood sugars are really high, patients think they’re having hypoglycemia, and it’s the blood sugars coming down to normal. Sometimes they treat without testing, the blood sugar goes up, and then you have this roller coaster effect that we also have to break.
Anne Peters, MD: Can I say 2 things? First, they’ve studied this when they’ve looked at rates of severe hypoglycemia or hypoglycemia that require hospitalization. It’s much more common for patients with type 2 on insulin than it is for patients with type 2 on sulfonylurea agents. Unsurprisingly, it seems worse if they’re on both insulin and a sulfonylurea because you’re hitting them twice. The difference between insulin-induced hypoglycemia and sulfonylurea-induced hypoglycemia is that the sulfonylurea-induced hypoglycemia can last for days because those patients are on a longer-acting sulfonylurea. I’ve had some seniors with impaired renal function who had to stay for 5 days in the hospital getting dextrose intravenously. In those cases, where it’s because of sulfonylurea, where there are more severe episodes because of a sulfonylurea agent, they end up hospitalized and have a fairly long course before they’re better. As Davida says, it’s important to look at everybody who’s on an agent that can cause a low and figure out why, what happened, and what treatment is necessary to get them better.
Peter Salgo, MD: One of the things that can sneak up on you—of that list of predispositions to hypoglycemia—is renal function deterioration, because 1 of the things that happens to diabetics over time is that their GFR [glomerular filtration rate] goes down. The half-life of these drugs increases; the insulin hangs around longer, and the sulfonylureas hang around longer. That can sneak up on you. You’re taking a dose that in the past you thought was OK, right? Somehow, it’s doing things to you that it never used to do. Is that a real feature of this, and is it a real problem?
Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM: Absolutely. If I have someone who has been steady on treatment and suddenly is having lows, part of my evaluation is to say, “Wait a minute, has something happened to the liver with glucose production or has something happened to their kidney with the clearing of medication?” I don’t see anything in the history that tells me why they would be having more lows. Absolutely, both of those should be in consideration if you have someone who has a sudden change in their control, specifically related to hypoglycemia.
Peter Salgo, MD: Elaine, you went through some of the common symptoms of hypoglycemia, but what I’d like to do is lay out once, as bullet points, the common symptoms of hypoglycemia that you see in pediatrics. The adult doctors, too, can lay that out for us. What do clinicians have to watch for?
Elaine Apperson, MD: We need to watch for elevated heart rate, excessive sweating, excessive hunger, nausea, vomiting, confusion, unresponsiveness—especially unresponsiveness—seizures, blurred vision, feelings of anxiety, and headache. Sometimes they will appear very pale. They may have altered heart rhythms, numbness or tingling, tremors, slurred speech, lack of coordination, or unsteadiness. All those things can happen. I’ll add to what Jay said. For pediatrics, 1 other consideration from a medical standpoint, if you see altered insulin needs, is adrenal insufficiency, which is also an autoimmune condition that some patients with type 1 diabetes may develop. This is a lack of adequate cortisol production, which also leads to hypoglycemia, adrenal insufficiency, or for a patient who’s a type 1 diabetic, it will cause them to have hypoglycemia.
Peter Salgo, MD: I always thought that if you gave too many steroids, you get hyperglycemia, not hypoglycemia.
Elaine Apperson, MD: You do, but these people start developing the lack of an ability to produce cortisol and therefore they develop hypoglycemia. If they’re taking insulin, their insulin needs would diminish, and therefore if you don’t change their insulin, they’ll have hypoglycemia.
Peter Salgo, MD: Got it. This is probably a good point to tell all of you on this panel that I’m in awe because diabetes is too complicated for me. Give me heart disease; I get that. But everything is a moving part here, right? The adrenals are a part of this, the liver is a part of this, the kidney is a part of this, and the sugar is simply floating in response to all this. How do you guys keep it all together? How do you keep all these parts separate? Do you?
Elaine Apperson, MD: One thing I tell patients and parents—especially parents who are engineers—is that they play a very small part in blood sugar control. Anything that can change your pulse can change your blood sugar, so you’re talking hormones, adrenalin—anything that can change anything internally has an impact on your blood sugar. If our patients can’t figure out why their blood sugar was 288 mg/dL last night, because they did nothing differently from the night before, and the night before it was 82 mg/dL, they may not ever know. That’s OK, and we just have to accept that.
Peter Salgo, MD: That makes me feel much better.
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Transcript Edited for Clarity