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Type 1

At Risk for Hypoglycemia? Here’s How to Best Manage It, According to Experts

Low blood glucose levels can put the lives of people with diabetes in danger. Understand why hypoglycemia and hypo unawareness happens, and what therapies exist to overcome this complication.

The first successful injection of insulin 101 years ago saved the life of a young man at Toronto General Hospital. But since then, the risk of hypoglycemia, or low blood sugar, continues to threaten the lives of people with diabetes.

Hypoglycemia is defined as a glucose value below 70 mg/dL, and occurs when there is not enough glucose for a person’s cells to use for energy. Hypoglycemia can be caused by excess insulin, missing a meal, exercise, alcohol, certain medications (sulfonylureas), and other factors.

Many people even experience “hypoglycemia unawareness” or “impaired awareness of hypoglycemia” which is when they are unable to recognize the symptoms of low blood sugar. About one in five people with type 1 diabetes and one in ten with insulin-treated type 2 diabetes report experiencing hypoglycemia unawareness.

Technology such as continuous glucose monitoring (CGM) and automated insulin delivery (AID) has the potential to reduce the risks of hypoglycemia unawareness and the consequences of developing it. On May 16, diaTribe hosted a Musings panel, “Managing Hypoglycemia and Hypo Unawareness: Is Technology Enough?” that explored the definitions of hypoglycemia, the clinical symptoms, the concept of hypoglycemia unawareness, and how technology has reduced the risks of this complication. The panel included: Pratik Choudhary, MBBS, MD, FRCP, professor of diabetes, University of Leicester (UK) Jason Gaglia, MD, MMSc, endocrinologist and researcher, Joslin Diabetes Center (Boston) Lisa Hepner, director, producer, and writer, The Human Trial Eritrea Mussa, social media manager, The diaTribe Foundation Moderator: Alan Moses, MD, FACP, Board Chair, The diaTribe Foundation | Past Chief Medical Officer, Joslin Diabetes Center and Novo Nordisk Watch a replay of the panel, and subscribe to our YouTube channel for more panel coverage.

Defining hypoglycemia (low blood sugar)

Experts have established three levels of hypoglycemia over the last decade:

  • Level 1: Glucose values between 70 mg/dL and 54 mg/dL. This is when a person with diabetes may start to experience hormonal changes and possibly symptoms such as anxiety and sweating.
  • Level 2: Glucose values less than 54 mg/dL. According to Gaglia, “You may or may not have symptoms, but it’s the point at which you’re not getting enough glucose to your brain” (also known as neuroglycopenia).
  • Level 3: Known as severe hypoglycemia in which glucose levels are so low that a person can’t function normally and may even lose consciousness. The person requires assistance from somebody else.

When a person with diabetes has experienced an episode of hypoglycemia, it can potentially impact their care. “Severe hypoglycemia begets severe hypoglycemia, so I need to be more careful with that person because they could have more severe hypoglycemia. I need to be more cautious in the recommendations I give around insulin with that person,” said Gaglia.

Devices like CGMs now allow people to more immediately see when they are low and respond to it appropriately. “If you feel symptoms and do a finger prick and your glucose is 54 mg/dL, you don’t know how long you’ve been at 54 before you had those symptoms. A CGM allows you to see how long you’ve been at that level, in range and out of range,” said Choudhary.

Managing a fear of low blood glucose

For people with diabetes, learning about hypoglycemia and having an episode can be a scary experience. Hepner, who has had type 1 diabetes for 32 years, described her own personal experience learning about hypoglycemia. “I watched a video on hypoglycemia, and it was a stark representation of what could happen that had a profound impact on how I looked at hypoglycemia.”

Experiencing hypoglycemia can weigh heavily on people with diabetes. And it can be especially challenging for people with diabetes to recognize the symptoms of low blood sugar and know how to respond to them.

Even Hepner and Mussa, who’ve both had diabetes for several decades and who both wear CGMs, experience episodes of severe hypoglycemia.

“I feel like a failure, because how does someone with all of this technology not get it right?” said Hepner.

Hypoglycemia unawareness

Mussa started developing hypoglycemia unawareness – a condition wherein someone can't tell when their blood glucose gets low so they don't know they need to treat it – when she was a teenager. She still experiences it.

“How could someone with diabetes for this long still be having these episodes? At 30 years old, you’d think after having type 1 for 21 years that it wouldn’t be as frequent but it is still something I often think and worry about,” said Mussa.

Some people are at greater risk for hypo unawareness, according to Choudhary and Gaglia. If you frequently experience hypoglycemia, your body can lose its stress response to it, which can prevent your body’s ability to recognize these events and symptoms when they occur. In short, hypoglycemia unawareness often happens because the brain accommodates episodes of hypoglycemia and no longer recognizes it.

“Hypo begets hypo. Once you have one episode, it predisposes you for the next episode,” said Gaglia.

Gaglia described how he is able to predict the onset of hypoglycemia unawareness in people with diabetes. “I look at the duration that they have had diabetes. People who have had it for longer are at higher risk. Certain medications may predispose. I also look at their level of glycemic control,” he said. “If they have an A1C of 5.5, I congratulate them but then I look at their CGM data. They might not know they are having hypoglycemia, but then we look at their CGM and find these episodes.”

This is one reason why, in addition to their A1C, people with diabetes should monitor their time in range with particular attention to time very low in range.

Conversely, if you don’t have a lot of hypos, you can regain those symptoms of being low. “The best thing you can do to avoid episodes is keep your TIR above 70%,” said Choudhary. The good news is that it’s possible to restore awareness and the warning signs of low blood sugar.

Much of the issue around hypoglycemia is psychological for people with diabetes. “We’ve learned that extreme episodes of hypoglycemia are incredibly rare. There’s a balance between ‘hypoglycemia can be life-threatening (very rarely)’ and how scared you are of hypoglycemia,” said Choudhary. “The risk versus the fear is often out of proportion. People who have a lot of fear are actually low risk and vice versa.”

Time Below Range of more than 7% can indicate a high risk of hypoglycemia unawareness. The current recommendation is to try and limit this to less than 4% (less than 1 hour per day).

The role of technology in reducing hypoglycemia

The FDA approved the first CGM system in 1999. This has allowed people with diabetes to more closely monitor their blood glucose levels. CGM has contributed to the lower levels of people with diabetes being hospitalized, as people can identify low blood glucose episodes that they may not have been aware of without a device.

“CGM has played a big role in preventing severe hypoglycemia but it’s not foolproof or failsafe,” said Moses. “No matter how good the technology, there are things we cannot completely control.”

“[Before having a CGM], I would run my sugars higher because I would rather be safe in the short term. I didn’t want to be low. I would think about the short term and not the long term,” said Hepner. “Now with my CGM and my phone, I am very aware of the range I need to be in to avoid complications.”

AID or hybrid closed-loop systems have also impacted diabetes management in terms of working to reduce hypoglycemia. This system uses a CGM and smart algorithms to automatically adjust and deliver the insulin you need.

“The best way to describe it for a lot of my patients is ‘liberating.’ It gives people more freedom. While using these predictive algorithms, we can be more aggressive because they’re less likely to experience hypo. It liberates people from some of this fear that they are going to cause hypoglycemia,” said Gaglia.

However, technology is not always perfect and hasn’t liberated everyone from the issue of hypoglycemia.

“There’s a human here still dealing with this. I’m not a perfect human. Sometimes I overshoot it on the insulin,” said Mussa, who is on an AID system. “Individualized therapy for each patient is so important.”

And even with all the technology available, it can be challenging, especially mentally, to be constantly fully in tune with the device and ultimately manage blood glucose levels.

“It’s this job that I can never take a break from,” said Mussa.

The quest for a cure

The concept of a “cure” in type 1 has been around for decades and the science behind it has rapidly progressed.

Research has shown that islets from pancreas donors can restore normal or near normal glucose control and that stem-cell derived beta cells can do the same. In fact, researchers and regulatory requirements place substantial emphasis on the presence of hypoglycemia unawareness when they enroll patients into their clinical trials.

One factor used to determine whether an individual is a candidate for pancreatic transplantation or investigational islet transplantation is the presence of hypoglycemia unawareness. This approach is based on a benefit/risk profile that tries to maximize the benefit (in this case reducing or removing the risk of severe hypoglycemia as a benefit) versus the risk associated with systemic immunosuppression for a therapy (beta cell replacement) that may not succeed.

“In terms of cost, I can see the argument that you need to be in a place where the risk of not doing anything is far worse,” said Choudhary. “Things are moving forward and we are getting to where the requirement for immunotherapy is lower.”

“Many of the people who were referred to us for islet transplantation did not need it; they needed to see an endocrinologist,” said Gaglia.

Many people who are eligible for transplantation may still decide to opt out as they are weighing the risks between having type 1 diabetes versus, as Gaglia calls it, “the disease of immunosuppression.”

“It’s the devil you know versus the devil you don’t know,” he added.

However, there are newer therapies being developed that won’t require immunosuppression, which will change this conversation and shift the benefit/risk calculation.

Still, understanding the challenges that people face struggling with hypoglycemia has motivated Hepner to help find a cure for diabetes.

“In terms of developing new therapies, I wouldn’t even say to develop new ones. I would say find a cure,” said Hepner. “I would love to put more time, effort and money into finding that cure, because I think it’s closer than we think.”