Hypoglycemia Working Group Statement - Diabetes Core Update Special Edition 10/29/2013

Summary

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Diabetes Core Update – Special Edition: Hypoglycemia Working Group Statement

Podcast: Diabetes Core Update
Date: October 29, 2013
Host: Dr. Neil Skolnik
Guest: Dr. Elizabeth Seaquist, Professor of Medicine, University of Minnesota

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Episode Overview

This special edition of the Diabetes Core Update podcast centers on the landmark statement by the American Diabetes Association (ADA) and the Endocrine Society regarding hypoglycemia in diabetes, published in the May 2013 issue of Diabetes Care. Dr. Neil Skolnik interviews Dr. Elizabeth Seaquist, the report's first author, to discuss the group’s recommendations, focusing on hypoglycemia’s definition, long-term risks, implications for clinical targets, and strategies for clinician and patient management.

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Key Discussion Points & Insights

1. Defining and Reporting Hypoglycemia

Timestamp: 02:25–03:18

• The working group deliberated extensively on the appropriate blood glucose threshold for hypoglycemia.
• The agreed “alert value”:
  • Blood glucose <70 mg/dL (3.9 mmol/L)
  • Chosen as the actionable threshold to prompt intervention before severe symptoms arise.
  • Distinction between definitions for clinical care versus research; <70 is most crucial for clinicians and patients.
• Quote:

  “People do get symptoms of hypoglycemia at this level, but it’s not so low that a person is so hypoglycemic they’re unable to take action.”
  — Dr. Elizabeth Seaquist [02:42]

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2. Short and Long-Term Implications of Hypoglycemia

Timestamp: 03:18–04:31

• Acute consequences: confusion, unconsciousness, seizures, and death.
• Newer data—especially from the ACCORD study—links hypoglycemia with higher mortality risk, especially in older adults with comorbidities.
• These findings challenge aggressive glycemic targets in vulnerable patients.
• Quote:

  “The ACCORD study demonstrated that hypoglycemia increased the risk—people with hypoglycemia had a higher mortality risk than those who did not have hypoglycemia...”
  — Dr. Seaquist [03:57]

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3. Hypoglycemic Unawareness (Hypoglycemia-Associated Autonomic Failure)

Timestamp: 04:59–06:48

• “Hypoglycemia unawareness” occurs after repeated low blood glucose episodes.
• Each hypoglycemic episode reduces the body’s counterregulatory response, making recognition of subsequent lows harder; the first symptom could become unconsciousness.
• Importance for primary care providers: ask patients about their lowest glucose levels and whether they ever fail to notice hypoglycemia.
• Quote:

  “If your patients are having values in the 50s and they say, ‘I didn’t know I was low, I felt fine,’ that’s a warning sign...that really puts them at risk for unconsciousness as the first symptom.”
  — Dr. Seaquist [06:26]

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4. Implications for Treatment Targets

Timestamp: 06:48–08:55

• Historical approach: aggressive A1C goals (<7%) for all.
• Updated thinking: personalized targets, especially for older adults/multiple comorbidities, are safer.
• Intensive targets in high-risk patients (per ACCORD) increased mortality by 20%.
• Balance intensity of glycemic control with individual risk for hypoglycemia.
• Medication class and risk:
  • Metformin: very low risk for hypoglycemia.
  • Sulfonylureas & insulin: higher risk—calls for caution.
• Quote:

  “Many organizations are now saying...you need to take a look at all the comorbid[ities], the life expectancy of the person, the social support system, before you really come up with the right A1C target.”
  — Dr. Seaquist [08:36]

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5. Strategies to Help Patients Avoid Hypoglycemia

Timestamp: 09:53–10:45

• Patient education:
  • Symptoms and levels of hypoglycemia.
  • Treatment protocols (e.g., “15-15 rule”: 15 grams carbs, recheck in 15 minutes).
  • Importance of reporting all hypoglycemia episodes to clinicians.
• Clinical response:
  • Frequent hypoglycemia or hypoglycemic unawareness = consider less aggressive targets and reevaluate medication regimens.
• Quote:

  “If people are having frequent hypoglycemia and no longer have symptoms...it’s time to step back a bit.”
  — Dr. Seaquist [10:32]

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6. Core Takeaway and Clinical Call-to-Action

Timestamp: 10:45–11:49

• Consistent and proactive inquiry about hypoglycemia at every diabetes visit is crucial.
• Selection of glucose targets and medication regimens must take risk of hypoglycemia into account.
• “The single most important takeaway” is the heightened awareness of hypoglycemia’s clinical significance and impact on patient management.
• Quote:

  “...The increasing recognition, based upon an abundance of evidence, of the importance of hypoglycemia and the fact that this awareness should influence our choice of treatment targets for patients and also lead us to ask about hypoglycemia at each and every diabetes related visit.”
  — Dr. Neal Skolnik [11:17]

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Memorable Quotes

• On the alert threshold:

  “The value is less than 70 in the statement...I think the 70 value is the really important number to remember.”
  — Dr. Seaquist [02:56]

• On clinical vigilance:

  “That’s not a good thing. That’s a warning sign that they’re having recurrent hypoglycemia sufficiently often to cause them to have this blunted response that really puts them at risk for unconsciousness as the first symptom.”
  — Dr. Seaquist [06:22]

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Segment Timestamps

| Time | Topic | |------------|------------------------------------------------------| | 00:01–00:32| Introduction and episode purpose | | 02:25–03:18| Hypoglycemia: Definition and reporting | | 03:18–04:31| Short/long-term risks; ACCORD trial discussion | | 04:59–06:48| Hypoglycemic unawareness explained | | 06:48–08:55| Adjusting A1C targets based on hypoglycemia risk | | 09:53–10:45| Patient education and response strategies | | 10:45–11:49| Key takeaways and clinical action |

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Final Thoughts

This episode highlights a critical shift toward person-centered care for diabetes, emphasizing that hypoglycemia is not just a complication, but a factor that often dictates optimal clinical strategy. Through clear case examples and guidance, Dr. Seaquist and Dr. Skolnik advocate for tailored glycemic goals and vigilant ongoing assessment, particularly in higher-risk populations.

For more in-depth content and the full statement, listeners are encouraged to visit diabetesjournals.org.

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Transcript

[A]

Welcome to the American Diabetes Association Core Update. While we usually go over the most important articles from the core journals published by the American Diabetes association, today we will cover Hypoglycemia and Diabetes, a report of a workgroup of the American Diabetes association and the Endocrine Society published in the May issue of Diabetes Care. Joining us today will be our usual host, Dr. Neal Skolnick, as well as first author of the paper, Dr. Elizabeth SeaQuest.

[B]

Dr. Skolnick, we've got a great topic for this special edition of Diabetes Core Update. Today we're going to discuss Hypoglycemia and Diabetes, a report of the work group of the American Diabetes association and the Endocrine Society that was published in the May issue of Diabetes Care. Hypoglycemia has been increasingly recognized over the last decade to be an important consequence of intensive treatment of hyperglycemia, and a consequence of hypoglycemia is, in turn, many effects, including potentially a higher mortality rate in people who experience severe hypoglycemia. Due to these concerns, the American Diabetes association and the Endocrine Society put together a work group to discuss specific recommendations with regard to this important issue. We'll discuss some of these recommendations over the next 20 minutes. Today we had the opportunity to talk with Dr. Elizabeth Sequist, who is the first author of the working group statement. Dr. Sequist is a professor of medicine in the Division of Endocrinology and Diabetes at the University of Minnesota School of Medicine. Since we only have about 20 minutes to discuss the statement, we'll restrict our discussion to the highlights of the statement. And I'd like to encourage our listeners to go to the American Diabetes association [e-mail] to download and read the full statement. Since the statement was organized to answer clinical questions, we'll follow the organizational outline for our discussion. For our first question, Dr. Sequest, how should hypoglycemia in diabetes be both defined and reported?

[C]

Well, the working group had a lot of discussions about this issue because there's many different ways of defining hypoglycemia. But we came down to the final decision that the alert value that people should pay attention to is a blood glucose level less than 70 milligrams per deciliter or 3.9 millimoles per liter. The reason we picked this level is that it clearly is a lower level. People do get symptoms of hypoglycemia at this level, but it's not so low that a person is so hypoglycemic they're unable to take action, and that's why we really think of it as an alert value. So the value is less than 70 in the statement. We have a number of different ways of qualifying different kinds of hypoglycemia, which really were written more for, I think researchers than clinicians and people might be interested in that. But I think the 70 value is the really important number to remember.

[B]

That's helpful. I believe there's a lot of confusion around that issue out there and that helps clarify it. Probably the core of what the working group statement addressed is both the short and long term implications of hypoglycemia for patients with diabetes. Can you discuss a little bit about those issues?

[C]

That's right. We've known for a long time that when people get hypoglycemic as a result of their insulin treatment or treatment with other medicines for diabetes, people get confused, people can become unconscious, have seizures, and we know that there are deaths related to hypoglycemia that we've known for a long time. But in recent years, there have been large clinical trials done in patients with type 2 diabetes. And one of them, the ACCORD study, demonstrated that hypoglycemia increased the risk of people with hypoglycemia had a higher mortality risk than did people who did not have hypoglycemia, which has really raised questions about the safety of intensive glucose targets for older patients with multiple comorbidities. And that's something we wanted to highlight in this statement because those are the patients so many of us see, older people who have multiple problems, and we just have to think twice about where we want our targets to be.

[B]

That's a really important point. One of the things as a primary care physician that I found to be both interesting and important was the issue of hypoglycemic unawareness and the term hypoglycemic autonomic failure. It's not an issue that many of us in primary care think a lot about, though I'm sure that we do see this. Can you talk about what hypoglycemic unawareness is, as I think it has important implications for what we do when our patients report hypoglycemia.

[C]

Absolutely. It's another really important part of the statement because we did want the primary care docs to get an idea that they need to start looking for this. So what hypoglycemia associated autonomic failure is. It's a long name and some people call it hypoglycemia unawareness. It's a situation that occurs when people are exposed to recurrent hypoglycemia. What really happens is every time a person has a low blood sugar, the glucose level that is necessary to elicit that response, the symptom response, and the counter regulatory hormone response to a subsequent episode of hypoglycemia is reduced. So, say today you get a glucose value of 65 and you have shakiness and you know you're hypoglycemic and you treat it and it's over. Well, the next day you might have to get down to 60 or 50 or another lower level. And the lower and lower glucose level a person requires to begin to get symptoms of hypoglycemia brings them ever more closer to that level where the first sign is unconsciousness. And so that's very dangerous for patients. And so, as a primary care doctor, something you can do, and there's a whole table in the statement that we put in there just to help primary care doctors deal with the situation. There are questions you can ask your patients to try and understand if they're having such frequent hypoglycemia that they don't get symptoms anymore. Simple questions like what's the lowest blood sugar you've ever gotten where you didn't even know your sugars were low? If your patients are having values in the 50s and they say, I didn't know I was low, I felt fine, that's a warning sign. That's not a good thing. That's a warning sign that they're having recurrent hypoglycemia sufficiently often to cause them to have this blunted response that really puts them at risk for unconsciousness as the first symptom.

[B]

That's a scary thought with important implications that a low glucose value is really an alert value that needs to be addressed. That really leads us to the next question, which is, what are the implications of hypoglycemia on treatment targets? That is, what should we do when patients report low blood sugars?

[C]

Well, I think when we see that in the past, when we used to think that the target for everyone was glucose values in the normal range on a 1Cs that were all less than 7, no matter what the risk of hypoglycemia. Practically, that's not true anymore. We don't have to. I think we have to be careful for those patients who look very much particularly like the patients enrolled in the Accord trial, because those patients who were randomized to the group where their A1C target was the intensive target in this study was less than. Those are the patients who had a 20% increased risk of mortality. We know that hypoglycemia was linked to that risk, although we don't know for sure that patients died because of hypoglycemia. There may be some other more complicated interaction, but what it tells me as a clinician is that older patients with comorbidities, we probably should not be targeting their A1C to less than 7 or certainly less than 6 if we're going to increase their risk of hypoglycemia. So for instance, someone who's being treated with metformin and gets to a value of six and their risk of hypoglycemia is really, really low, if not absent with hypoglycemia. So that's a person you may want to let get to a lower level. But if someone requires a sulfonylurea or an insulin to be added to their therapy to get their sugars into target, you're now putting them at risk for hypoglycemia. And you may want to think twice about how low you want them to go. And many organizations are now saying that you need to take a look at all the comorbid, the life expectancy of the person, the social support system, before you really come up with the right A1C target for an individual, because it shouldn't be the same for every person.

[B]

That's a really good point. I want to emphasize one of the things that you mentioned, and that's that some medicines have a higher risk for hypoglycemia than other medicines. In the American Diabetes Association's statement on medical management of hyperglycemia, which we reviewed here last year, they recommend evaluating medications and individualizing the use of medications based on a rubric that includes efficacy, cost, effect on weight, side effects, and emphasized looking at the risk of causing hypoglycemia. Some medicines, as you said, sulfonylureas and insulin in particular, have a much higher risk of hypoglycemia attached to them than some other medicine choices reported. Hypoglycemia should certainly cause us to review both choices of medicines and doses of the medicines used. So what strategies should be used to help patients avoid hypoglycemia?

[C]

Well, the first thing is people need to understand what hypoglycemia is, what the symptoms of the situation are, what the glucose levels that are associated with hypoglycemia. They need to know how to treat the hypoglycemia so that if it happens, they can reverse it the 15 grams of carb in 15 minutes and wait 15 minutes before you check and see if you've come up again. And they need to know that if they develop hypoglycemia, they need to let their doctors know so that they can determine if their target is really set right for them. Again, if someone's having recurrent hypoglycemia, that's a sign that you're setting them up to develop this hypoglycemia unawareness syndrome. And probably if people are having frequent hypoglycemia and no longer have symptoms of hypoglycemia when their blood sugars are in the symptoms 60s, it's time to step back a bit.

[B]

That's an important point. I want to thank you for joining us today on our podcast to recap for our listeners, we talked about the definition of hypoglycemia, a blood glucose of 70 or below, with or without symptoms. We talked about the effect of hypoglycemia on outcomes. And we discussed the ACCORD trial and the increased mortality of those randomized, the intensive group, and the increased mortality of those individuals who had episodes of severe hypoglycemia. And you just talked about management strategies, including lifestyle issues and choices of medicines. Probably the single most important takeaway point is the increasing recognition, based upon an abundance of evidence, of the importance of hypoglycemia and the fact that this awareness should influence our choice of treatment targets for patients and also lead us to ask about hypoglycemia at each and every diabetes related visit. Dr. Sequist, thank you so much for joining us.

[C]

Thank you.

[B]

It's been a pleasure for the American diabetes association. I'm Dr. Neal Skolnik. For more information on the working group statement on hypoglycemia, just go to www.diabetesjournals.org. thanks for listening.

[C]

Sa.