By Chris Kaiser, Cardiology Editor, MedPage Today
Transcript:CHRIS KAISER: I'm Chris Kaiser, MedPage Today, with a Clinical Context report on the Management of Diabetes, specifically hypoglycemia. I'm speaking with Dr. Farhad Zangeneh, the Medical Director of the Endocrine, Diabetes and Osteoporosis Clinic in Sterling, Va. Welcome, Dr. Zangeneh.
FARHAD ZANGENEH, MD: Thank you.
KAISER: First let me start with a broad question. Can you tell me about the problem of hypoglycemia, and why it is perhaps being overlooked by clinicians.
ZANGENEH: Excellent. Hypoglycemia, or low blood sugar, I like to call it the Rodney Dangerfield of diabetes, because the focus is always on high blood sugar, hyperglycemia, because diabetes mellitus, too, is all about the high sugar.
Hypoglycemia is, if you will, the side effect of diabetes management, because if you have too much insulin or a mismatch of insulin, or a mismatch of rendezvous of insulin and sugar, you have hypoglycemia. And of course we can talk about the impact of it and how that resonates for patients.
But we like to tell our patients we'd like you to be euglycemic -- to have normal blood sugar. Also, there is a huge body of evidence that talks about how variability or turbulence is also bad. So we want a euglycemic flow, we want to avoid peaks and valleys, and we'd like to avoid turbulence, and hopefully all of that will lead to good diabetes management and outcomes for the patients.
KAISER: Well, as an endocrinologist, by the time the patients come to you, they've probably been to their primary care doctor many times, dealing with their diabetes. What would you say is their education level on hypoglycemia?
ZANGENEH: I think the American College of Endocrinology, with a grant from Merck, has put together this web site called BloodSugarBasics.com. And this web site did a survey last year, and found that most people with diabetes were not aware of signs and symptoms of hypoglycemia.
Education on diabetes as a whole can be improved. But education on hypoglycemia needs to be improved even further, especially in light of the most recent guidelines that have come out. They all recommend aggressive management without hypoglycemia, without weight gain, and personalized. So individualize your management with a big stress: please do not cause hypoglycemia. Please do not cause a weight gain in the setting of type 2 diabetes, obesity in the background.
KAISER: So how do we define hypoglycemia?
ZANGENEH: The exact terminology is a bit debatable: blood sugar to be less than 50, less than 40, less than 60 milligrams per deciliter. But it is a combination of low blood sugar with symptoms of neuroglycopenia. That means the individual does not recognize where he is, where she is, as well as resolution of symptoms once you correct the hypoglycemia.
But collectively we like to say sugar less than 60 mg/dL; or perhaps for the older population, less than 70.
KAISER: So a lot of the management of hypoglycemia really falls to the patient. What happens when the patient is in the doctor's office? How can that relationship ensure that that patient won't go into a hypoglycemic state?
ZANGENEH: Excellent point. Insulin and sulfonylurea are capable of causing hypoglycemia under certain settings. So if you have type 1 diabetes -- which our focus of talk today is about type 2 -- but if you have type 1 diabetes, you're on insulin. You should have glucagon at home. You're fully educated about always injecting insulin with food, not skipping meals; the full protocol of making sure the rendezvous of time and place of insulin and food is not mismatched.
For type 2 diabetes, we can classify our diabetes medications with those that have the potential of hypoglycemia -- insulin, sulfonylurea -- and those that are euglycemic. Euglycemic is all other categories of diabetes medication: GLP-1 inhibitors, DPP-4 inhibitors, colesevelam, acarbose (Precose) and other alpha-glucosidase inhibitors, and the TZDs.
So to go back to your question, you need to make sure the patient has a glucometer, is educated on the signs and symptoms, is educated on nutrition, exercise, things that cause hypoglycemia, and what to do. So they have the plan.
But the best way to treat hypoglycemia is to prevent it. So when it does happen, I usually bring the patient back and we go through a complete audit. Why did it happen? How did it happen? Let me look at your medication list. Let me look at it again. So this way we try to focus on the cause, educate the patient to prevent it, because hypoglycemia has a number of terrible consequences.
KAISER: So let's talk about some of the signs and symptoms, and perhaps how the patient's clinicians can inform them about this so that they are ready. And do they have some kind of an emergency pack or something that can help them once they become hypoglycemic?
ZANGENEH: First you have to tell the patients about the alert. Patients might feel nervous, irritable, restless, cold sweat. They may feel hungry. They may get a headache. Everybody's symptoms are different. And of course, what you do when you feel like that? You will check your blood sugar to confirm.
You would rescue with a caloric liquid. You can have some juice. You can have a sugar tablet. People with type 1 diabetes, they can perhaps become unresponsive. There is a glucagon emergency kit that is administered to the patient by a friend, family, and loved ones, but that's an extreme case.
But if you know you're going low, you know that alarms are coming, you know your body. One of the things I always educate my patients: know your body, know your pattern, know your routine, listen to your symptoms, and be aware of it, so that's part of the education.
And of course, the reasons for this. Certain medications are "Today I exercised too much. Today I skipped my meal. Today, by accident, I took an extra pill." A lot of things can cause low blood sugar. "I'm having a colonoscopy. I didn't eat. I'm on a low calorie diet. The food didn't look good, so I skipped it." All of these.
But then the other issue here: why is hypoglycemia bad for you? When your blood sugar is low, your catecholamines and adrenaline are elevated to rescue you off the low. And adrenaline and catecholamines are not good for a fragile heart or people with diabetes; they can cause dysrhythmias, premature ventricular contractions. In recent trials, there were poor outcomes with hypoglycemia. Three different trials showed that hypoglycemia may increase cardiovascular mortality, so this is not just a benign process.
Hypoglycemia promotes hunger. Hunger leads to feeding. Feeding worsens obesity. Hypoglycemia leads to eating when you are not even hungry, so brings in calories when you are not really interested, but the promotion of hunger means you're perpetually in search of food.
Hypoglycemia begets hypoglycemia. The more low you get, you lower the threshold of subsequent hypoglycemia; that's not good. And hypoglycemia reduces your ability to tell your lows, and that is the nightmare scenario. Why is that? You don't know you're going low. One minute I'm sitting here having an interview with you; the other minute I will not recognize who you are or where I am without the warning. Remember, all the warning signs that I shared with you will be gone because of neuroglycopenia.
So the reason we don't like hypoglycemia is the cardiovascular issues, the hunger, the dysrhythmias, neuroglycopenia, frequent hypoglycemic episodes.
And the other last reason is the more episodes of hypoglycemia you have, hemoglobin A1C is falsely lowered. That reminds me of a patient I saw -- hemoglobin A1C, 6%, type 1 diabetes -- and I said, "Who would refer such a good patient?" But my first question was, "Do you have hypoglycemia?" And actually the patient's spouse answered, "Let me answer that. He is low every day, paramedics know my name, and they actually have the key to our house because they're there all the time."
So the point is hypoglycemia falsely lowers your A1C and that is an important concept.
KAISER: You mentioned about the cardiovascular risks. What about cardiologists and their awareness of hypoglycemia? In your practice and meeting your colleagues, what have you found out about that?
ZANGENEH: Our cardiology colleagues are very much aware of hypoglycemia, because they know that hypoglycemia can lead to dysrhythmias. A number of cytokines are released, and it's bad for the main organ that they're trying to protect, which is the heart and the cardiovascular system.
Nephrologists are also very much aware of this, because when you have renal disease, the half-life of insulin is increased. And people with renal disease, because of increased half-life of insulin and reduced renal gluconeogenesis, are also at an increased risk of hypoglycemia. So multiple specialty societies and professions are aware, but the point is because we are living in a golden era of diabetes, the majority of the strategies we use for management of type 2 diabetes do not cause hypoglycemia.
So, we'd like to follow a pharmacopathophysiologic approach to diabetes: fix the endocrine system and fix the insulin resistance, and we like to use agents that, for the most part, do not cause hypoglycemia.
But there comes a time when we may have to use insulin in type 2 diabetes. So hypoglycemia is part of diabetes management. We know about what to do when it happens, but first of all, we must do everything we can to prevent it.
KAISER: And let me just ask, why would a patient with diabetes be seeing their primary care physician rather than an endocrinologist?
ZANGENEH: There are not enough endocrinologists out there. We are in the middle of a diabetes epidemic. So the more people know about diabetes, the better we can work as a team. Sometimes the primary care physician is tagging the endocrinologist because they need help. Sometimes it's a difficult patient. Sometimes they need a second opinion. Sometimes the diabetes is advanced and you need to incorporate multiple treatments that the primary care physician may not be familiar or comfortable with.
Or sometimes the patient directly comes to an endocrinologist: "I don't need to have a referral. That's when I came and I saw you." But I make sure the patient has a primary care physician and I like to work with that primary care physician; again, we work as a team.
So consults can come through from the primary care physician, from a cardiologist, from a nephrologist, from a dentist, from an ophthalmologist, or patient can direct themselves directly to an endocrinologist. And again, it can have many different reasons why you are there, but again, it's very important that everyone works together to improve the lives of people with diabetes.
KAISER: And just a final question. In your experience, what percentage of patients will experience hypoglycemia? Is it high? Is it low?
ZANGENEH: It is very high, and many times people are not aware, even my own patients. "I see that you've been running low while you're on insulin. Why did you not let me know?" Well, the patient responds, "I thought you were a high blood sugar doctor, you didn't care about the lows."
Or I run into a patient of mine, a graduate of a very excellent institution. "Do you have any lows?" "Yes, Doctor, I have them every day. And every day, one day, I have cookies, one day I have soft drinks, one day I have ice cream." So he thought it was part of daily life, and so instead of eating boring sugar tablets, he set up nice little treats for himself.
But hypoglycemia should be reported, because if it is reported and it is a consequence of my treatment plan, I would modify the treatment plan. But if it is happening because of something the patient does, the patient needs to be educated about the skipped meals, et cetera, et cetera.
But we are lucky because we are in an era where the majority of our diabetes management tools, pharmacotherapies for type 2, are not likely to cause hypoglycemia, with the exception of insulin and the sulfonylureas.
But if you're on insulin, very high risk; on sulfonylurea and secretagogues, very high risk; bad liver and bad kidney, very high risk. The folks who are not on insulin or sulfonylureas, good kidney, good liver, and on new glycemic drugs, their risk is very low. But collectively, the risk is there, and many times it goes unnoticed. "I just didn't feel well, so I had some juice and I was fine."
So it goes back to the concept if the tree fell and no one was there to hear the sound, did it really make a sound? Yes, it did, but there was no one there to observe it or record it, so I think that's the concept of hypoglycemia.
But even if it is unnoticed, it is not benign because it can cascade out to much bigger problems over time.
So that's why I think it is important that the medical community, as well as the patients, pay attention to this and be aware of it, because I like to say that hypoglycemia is the greatest side effect of any diabetes treatment, and we can avoid it by trying to be as close to normal without causing hypoglycemia.
KAISER: So it really sounds like it's very important for the clinician, whichever clinician that the diabetic patient sees, to ask the right questions, really has to get granular with what's going on with that patient.
ZANGENEH: Absolutely.
KAISER: Dr. Zangeneh, thank you so much for having this conversation.
ZANGENEH: My pleasure. Thank you.
http://www.medpagetoday.com/clinical-context/Type2Diabetes/33423
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