The Hypoglycemic Fear Syndrome: Understanding and Addressing This Common Clinical Problem in Adults With Diabetes

Abstract

Although a broad literature on fear of hypoglycemia and its impact on people with type 1 or type 2 diabetes has accumulated over the past three decades, there has been surprisingly little guidance concerning how best to tackle this problem in clinical care. The aim of this article is to begin filling this gap by describing the “hypoglycemic fear syndrome,” which we define as hypoglycemic fear that has become so overwhelming that it leads to avoidance behaviors and chronically elevated glucose levels. We begin by presenting several illustrative cases, describing the syndrome and how it is most commonly presented in clinical care, and detailing its most common precipitants. We then offer practical, evidence-based strategies for clinical intervention, based on the literature and our clinical experience.

Hypoglycemia is very common among people with diabetes (PWD) (1), and some degree of fear or worry about hypoglycemia is recognized as healthy and adaptive. Even mildly symptomatic hypoglycemia can be uncomfortable and unpleasant and can interfere with one’s ability to function effectively; as glucose levels drop further, such events can be potentially embarrassing, dangerous, and even life-threatening (2). Therefore, efforts to minimize or avoid hypoglycemia—especially severe hypoglycemia—are essential for successful diabetes management. However, problems occur when those worries and fears are excessive and when they then drive unhealthy management choices. Consider the following cases.

Maddie is 48 years old and married with one child, and she has had type 2 diabetes for 10 years. She has been on multiple daily insulin injections for the past 6 years. Several years ago, she had a severe hypoglycemic event, resulting in a seizure. Since then, she has been terrified of hypoglycemia, and her A1C has risen from 7.5 to 9.9%. She describes frequent “minor panic attacks,” during which errant body sensations signal to her that her blood glucose might be going low, although this is never the case when she checks her glucose. She admits to often omitting both basal and mealtime insulin, checks her glucose levels “constantly,” avoids exercise, and often binges before bedtime because of her fear that she will become hypoglycemic while sleeping. Although she is knowledgeable of the risks and genuinely wishes that she could lower her glucose levels, Maddie has resisted all recommendations from her health care team.

Fred is 32 years old, married with three small children, and employed as an engineer. He was diagnosed with type 1 diabetes at the age of 13 years. Since entering adulthood, he has been on an insulin pump and a continuous glucose monitoring (CGM) system and, until recently, maintained near-target glycemic levels (A1C values ranging from 7.0 to 7.3%). However, 9 months ago, he had a frightening severe hypoglycemic event while out trail running with his wife. Since then, Fred has reduced his premeal boluses by 50% (as he says, “just to be safe”), given up running and cut back on all other physical activity, raised his CGM low alert threshold from 80 to 130 mg/dL, and now overconsumes carbohydrates whenever he sees a downward trend arrow or feels “funny.” His A1C is now 8.6%. Of note, his wife has now developed significant insomnia as a result of her greater worries about overnight hypoglycemia, and their relationship has grown more tense.

Beginning with the groundbreaking work of researchers at the University of Virginia more than three decades ago, much has been learned about the phenomenon of hypoglycemic fear (3–5). It is now recognized that high levels of hypoglycemic fear are relatively common (6) and that cases like Maddie’s and Fred’s are not rare. However, the actual rates remain unknown because there are no well-established criteria for defining “high” levels. Evidence from self-report measures, including the Hypoglycemic Fear Survey (7) and the Hypoglycemic Attitudes and Behavior Scale (8,9), suggest that excessive hypoglycemic worry, an inexact term that aims to represent the wide variety of ways in which elevated fear or worry is categorized, ranges from 14 to 48% in adults with type 1 diabetes (9,10) and from 12 to 28% in adults with type 2 diabetes (8,11–13). In addition, as exemplified by Fred’s wife, fear or worry regarding hypoglycemia is not uncommon in spouses and partners of PWD (14,15). Hypoglycemic fear is associated with poorer quality of life (16–18) and, in many but not all studies, with elevated A1C (19,20). Indeed, while many PWD with high levels of hypoglycemic fear and worry fall into avoidance behaviors that lead to elevated glycemic levels (as seen in Maddie’s and Fred’s cases) (8,9), many do not. As one example, Hanna et al. (21) observed that higher levels of hypoglycemic fear in a sample of emerging adults with type 1 diabetes was linked to better self-care over time. This finding speaks to the complexity of hypoglycemic fear, to its many different “flavors,” and to their effects on glycemic management (22).

Several excellent reviews of the phenomenon of hypoglycemic fear already exist (20,23,24), and it is not the purpose of this article to provide another overview of this broad literature. Instead, we aim to address a critical gap; surprisingly little has been written about interventions to address high levels of hypoglycemic fear, and the manner in which such problems should be addressed in clinical care remains unclear. Therefore, the aim of this article is to present a series of practical clinical strategies for intervention, based on the available literature and our clinical experience. In particular, we focus our attention on the subset of individuals who are of greatest concern: those with chronically high levels of hypoglycemic fear who, like Maddie and Fred, are locked into a pattern of anxiety and avoidance resulting in elevated A1C.

We refer to this particular presentation of hypoglycemic fear as the “hypoglycemic fear syndrome” (HFsyn). People affected by HFsyn 1) report chronically high levels of hypoglycemic fear and 2) cope with that fear by keeping their glucose levels high and/or limiting their lives and activities to avoid any possibility that a hypoglycemic event might occur. As seen in clinical practice, such people may dramatically cut back their basal insulin delivery, underdose prandial insulin at meals, snack excessively to avoid possible low glucose, limit exercise and other activities, and check their glucose levels much more frequently than is needed or, if using CGM, check their readings compulsively throughout the day. Very likely, worries about hypoglycemia dominate their thoughts. As a result, fears and worries about hypoglycemia make it all but impossible for them to achieve target glycemic goals and thereby place them at high risk for negative clinical outcomes.

Recent evidence and our clinical experience suggest that major contributors to HFsyn include prior episodes of severe hypoglycemia (25), which may lead often to a reaction similar to post-traumatic stress disorder (PTSD) (26), impaired awareness of hypoglycemia (IAH) (27,28), generalized anxiety or panic symptoms (25,29,30), and difficulty with accurately perceiving key body sensations and/or frequent misattribution of benign body sensations, whereby even a slight change in heart rate, for example, may be interpreted as incipient hypoglycemia (31).

We view the core of HFsyn to be a loss of confidence in one’s ability to avoid or address severe hypoglycemia (32). This loss of confidence may stem from a sense that one can no longer easily trust one’s body to function appropriately, especially in potentially uncomfortable, embarrassing, or dangerous situations. In addition, PWD who experience HFsyn may no longer trust that the tools and treatments for addressing hypoglycemia will function expeditiously. Doom is always lurking; thus, one must remain hypervigilant.

To address HFsyn, we suggest that the major emphasis should be on enhancing PWD’s confidence regarding hypoglycemia—in other words, to help them regain a sense of comfort and safety. We suggest that two groups of strategies should be considered in this regard: BE SAFE strategies and FEEL SAFE strategies (Table 1).

TABLE 1.

Summary of Interventions to Address HFsyn

Intervention Strategies	Description
BE SAFE interventions
1. Optimize medications.	Review current medications and their use to identify medications that increase the risk of hypoglycemia, problematic polypharmacy, overbasalization, or over-bolusing.
2. Be prepared to treat appropriately.	Plan for suitable, easy-to-use carbohydrates and rescue medications to be readily available.
3. Encourage adoption of diabetes technology.	Initiate CGM or, when appropriate, an AID system.
4. Address IAH.	Facilitate scrupulous avoidance of low glucose levels over a limited period of time, while individuals with HFsyn learn to better identify and respond to early warning signs of hypoglycemia.
5. Establish a no-delay glucose value.	Identify an agreed-upon glucose value at which immediate action will always be taken to treat hypoglycemia.
6. Identify times of elevated risk.	Review glucose patterns to identify specific times or events associated with increased hypoglycemia risk and collaborate to problem-solve solutions.
FEEL SAFE interventions
1. Encourage adoption of diabetes technology.	Initiate CGM or, when appropriate, an AID system.
2. Engage in symptom discrimination.	Help people with HFsyn distinguish between the symptoms of hypoglycemia and anxiety and teach brief relaxation and distress tolerance strategies.
3. Evaluate hypoglycemia treatment practice.	Encourage PWD to consume their preferred high-carbohydrate treatment and note exactly how long it takes for their glucose levels to rise >50 mg/dL.
4. Initiate graduated behavioral exposure.	Start a slow, incremental return to normal activity, through which the person tolerates lower, closer-to-target blood glucose levels.

BE SAFE Strategies

When PWD are truly at high risk of severe hypoglycemia, it is not unreasonable for them to be fearful. For example, if Fred chooses to resume trail running at some point in the future, he may remain at high risk of further severe hypoglycemic episodes unless he is better prepared with strategies for avoiding or addressing such problems. Therefore, as a first step, the following six BE SAFE interventions that can reduce hypoglycemic risk should be considered.

1. Optimize Medications.

A careful review of a person’s current medications may identify certain older hypoglycemic agents such as sulfonylureas that could be safely discontinued or potentially switched for a newer agent with a lower hypoglycemic risk profile (33). It is well established that other commonly used medications, including β-blockers, could also increase the risk for hypoglycemia; therefore, those medications should be carefully evaluated as well (34). In general, health care professionals should consider the possibility that problematic polypharmacy might be increasing a person’s hypoglycemia risk. Finally, insulin types and dosages should be carefully evaluated. This includes the possibility that the continued use of older insulins such as NPH may be making it more difficult to avoid large glycemic swings. Overbasalization and/or overly aggressive mealtime doses could also be a problem. Finally, the patient may be inadvertently making use of insulin in a manner that enhances hypoglycemia risk (e.g., frequent stacking of fast-acting insulin [i.e., administering a dose while the previous dose is still active] because of frustrations with high glucose levels) (35,36).

2. Be Prepared to Treat Appropriately.

Severe events often occur when PWD do not have suitable, easy-to-use carbohydrates or a rescue medication readily available. Help at-risk individuals plan for carrying fast-acting carbohydrates such as glucose tablets or make certain that these items are pre-positioned where they may be needed, such as in a car, purse, or nightstand. Similarly, it is important to prescribe rescue glucagon and to make sure that PWD and their friends and family members have it available and on hand when needed. New glucagon products are available that are smaller, more convenient, and much easier to use than ever before, including one new formulation that requires no injection (37).

3. Encourage Adoption of Diabetes Technology.

CGM use has been shown to decrease the frequency of severe hypoglycemic events, nighttime hypoglycemia, time spent in the hypoglycemic range, and hypoglycemic fear and increase hypoglycemic confidence (38,39). Early evidence supports similar, if not stronger, benefits from the use of automated insulin delivery (AID) systems, which connect a CGM system and an insulin pump with a control algorithm to deliver insulin automatically based on real-time glycemic data (40). One important and often underused feature of most CGM systems is the opportunity they afford to share real-time glycemic data with selected family members and friends. Although teens and adults can be reluctant to share CGM data with their loved ones (fearing possible judgment, unwanted advice, and more), they may still find it reassuring to know that, in the case of a hypoglycemic emergency, a trusted friend or family member can be notified (41). In our recent clinical experience, initiating CGM or, when appropriate, one of the new AID systems, is a useful first intervention. Although these tools are rarely sufficient for resolving HFsyn, they can be a crucial step that undergirds most of the intervention strategies that follow.

4. Address IAH.

As noted above, an inability to reliably recognize the onset of hypoglycemia is recognized as one of the major contributors to severe hypoglycemia (28). Although it was originally presumed that IAH was irreversible, it is now known that the scrupulous avoidance of low glucose levels over a limited period of time can often restore awareness, at least to some degree (42). This is likely why the introduction of CGM alone, which has been shown to reduce time in hypoglycemia, can often reduce, although not necessarily eliminate, IAH. In a related vein, when IAH cannot be reversed through these approaches, patients can often learn to better identify and respond to early warning signs of hypoglycemia. Typically, these early warning signs are subtle autonomic or neuroglycopenic “brain sputtering” symptoms that may have been previously misidentified or unrecognized. Programs that include such training, such as Blood Glucose Awareness Training and Hypoglycemia Anticipation, Awareness, and Treatment Training, have been shown to reduce hypoglycemic risk as well as hypoglycemic fear (43,44).

5. Establish a No-Delay Glucose Value.

One crucial issue often concerns how an individual decides when it is time to take action and whether choosing to delay action is reasonable. For example, PWD may become aware that they are becoming hypoglycemic (through the experience of symptoms and/or seeing a low glucose value) but may opt to continue with their current activities because they do not yet feel “that bad” or they are “too busy” to interrupt what they are doing. This could be especially worrisome for PWD with significant IAH; for those individuals, the first obvious warning sign of hypoglycemia may be confusion (after glucose levels have already dropped precipitously, leading to moderate or severe neuroglycopenia), which may leave them unable to respond appropriately.

In either case, a severe hypoglycemic event is, unfortunately, the likely consequence. Therefore, we believe it is crucial that all at-risk PWD choose (ideally, in close collaboration with their health care provider) a reasonable glucose value, which might be identified via CGM or fingerstick blood glucose monitoring, at which they agree to take immediate action to treat, regardless of how inconvenient it may be or what they may or may not be feeling. If CGM is available, this action point may be a glucose value in combination with a glycemic trend arrow. In total, we suggest urging PWD to rely not only on their feelings or hunches, but rather on specific numbers that represent the need for urgent action.

6. Identify Times of Elevated Risk.

A careful review of PWD’s glucose patterns and history with hypoglycemia can help to identify the key contributors to past hypoglycemic events and, of equal importance, pinpoint when future hypoglycemia may occur, such as while sleeping or after exercise. Once these circumstances are identified, collaborative problem-solving may lead to helpful recommendations, including bedtime or pre-exercise snacks, adjustments to basal insulin doses, or the introduction of CGM. Individuals also need to be alerted to the fact that a single hypoglycemic event can put them at risk for another event in the near future; therefore, extra caution should be exercised after an event occurs.

Intervention programs that incorporate strategies such as these have often demonstrated significant benefits. For example, the HypoCOMPaSS study, focusing on adults with type 1 diabetes and a history of severe hypoglycemia and IAH, introduced a group-based comprehensive education program that emphasized: “Never delay hypoglycemia treatment, establish times of Extra risk, recognize Subtle hypoglycemia symptoms, and be Wary about detecting and preventing nocturnal hypoglycemia.” Over a 24-month follow-up period, rates of severe hypoglycemia fell 90%, and hypoglycemic fear dropped significantly (45).

FEEL SAFE Strategies

Helping PWD who are struggling with HFsyn to be safe often is not enough. In our clinical experience, we sometimes find that the BE SAFE strategies described above are not even necessary. Consider Maddie’s case. Given her current avoidance strategies and her elevated A1C, she is—practically speaking—at no risk of hypoglycemia. She is safe, but she still feels vulnerable, fearing that hypoglycemia could strike without warning. This feeling can be viewed as being similar to PTSD, where a single traumatic event can reverberate over years and continues to induce significant fear (26). In such cases, as Vallis et al. (46) have argued, the needed intervention is fear management rather than merely glucose management. In other words, to regain hypoglycemic confidence, PWD need to FEEL SAFE. To address this crucial aspect of HFsyn, four major interventions, which all follow from a cognitive-behavioral therapy framework, are suggested.

1. Encourage Adoption of Diabetes Technology.

The introduction of CGM and/or an AID system, although introduced above as a BE SAFE strategy, is also a FEEL SAFE strategy. In a recent review of quality of life benefits after CGM initiation, the one consistent finding was a significant, though modest, drop in hypoglycemic fear and/or an increase in hypoglycemic confidence (39). AID systems have been linked to similar improvements (40). Thanks to the availability of low glucose alarms, including the recent advent of predictive low glucose alarms, and the use of CGM trend arrows (which allow PWD to see where their glucose is heading, not merely where they are in the current moment), users can be alerted to impending low glucose levels at an earlier stage and therefore can respond more quickly. Combined with the documented reduction in time in hypoglycemia, PWD may also begin to feel somewhat safer from severe hypoglycemia.

Of note, the effect sizes for improved hypoglycemic fear and hypoglycemic confidence observed in recent studies have only been small to moderate (41), which is similar to what we see in clinical practice. We have also seen, however, that the use of CGM in HFsyn cases may on occasion be problematic, as some PWD may find certain elements of the CGM feedback (especially when observing a downward glucose trend) to be too anxiety-provoking. Also, with the rapid growth in the use of AID systems, we have begun to observe that the standard glucose target ranges set by the AID system algorithms may be too aggressive, at least initially, for individuals struggling with HFsyn. In such cases, using the system’s manual mode, or an exercise mode, for an initial period of time may be the wisest course. In total, although CGM and AID use can be essential for helping most PWD with HFsyn feel safer, they are rarely sufficient on their own.

2. Engage in Symptom Discrimination.

As was evident in the two cases described above, it is common for PWD to confuse errant body sensations with warning signs of hypoglycemia. This confusion may be because anxiety symptoms are often quite similar to early autonomic signs of hypoglycemia, with both arising via the same hormonal pathways. Maddie’s “minor panic attacks” are a good example of this, in which she found herself constantly wondering, “Am I having a low, or am I just frightened?” Fred was having similar incidents, although he did not view his recurrent experience of feeling “funny” as being linked to anxiety. In either case, it can be valuable to educate PWD about the similarities (as well as the subtle differences) between anxiety and hypoglycemic symptoms; then, through the introduction of in-office guided relaxation exercises, especially when a presumed early symptom of hypoglycemia first arises, PWD can often begin to better discriminate one group of symptoms from the other.

Shortly after Maddie began HFsyn counseling and first described her last experience with hypoglycemia, she immediately noticed that her hands and feet began to sweat, her chest tightened, and she became winded. Fearing the onset of hypoglycemia, she immediately reached for her glucose meter. Before she could reach it, her counselor intervened and asked her to first practice the brief, 1-minute relaxation exercise that had been taught to her in the previous session. Her symptoms quickly disappeared, which was a startling experience for Maddie; the quick reversal of her uncomfortable bodily sensations made her realize that her glucose was not likely to be severely low. Rather, it was anxiety about hypoglycemia—not actual hypoglycemia—that was causing these symptoms. She was encouraged to continue to practice the relaxation exercise at least once daily (to strengthen her ability to quickly address and reverse early anxiety sensations) and, when further symptoms arose, to try the relaxation exercise before pulling out her glucose meter or consuming glucose tablets or other fact-acting carbohydrates.

Anxiety about hypoglycemia can escalate very quickly, and asking people like Fred or Maddie to stop in the midst of such feelings and practice a brief relaxation exercise can be challenging. To help individuals with HFsyn gain a few precious seconds in which to reclaim perspective and thereby potentially choose the new behavior (e.g., relaxation practice) over the old behavior (e.g., binge eating), it is important to plan ahead by brainstorming with them about simple environmental cues that could be introduced. Fred, for example, found that affixing a small piece of adhesive tape with the words “Take a breath!” written on it to the bottom part of his CGM reader gave him the moment he needed to interrupt his cascading anxiety and practice his brief relaxation exercise (47). It is important to emphasize that such interventions should only be conducted with individuals who are not at very high risk of severe hypoglycemia.

3. Evaluate Hypoglycemia Treatment Practice.

PWD with HFsyn are likely to feel safer when they are assured that their preferred hypoglycemia treatment can be trusted to work as needed. Such assurance can only be gained when the effectiveness of the treatment is demonstrated in action. Therefore, conducting home or in-office “experiments” when a person is not hyperglycemic can be helpful. During these experiments, PWD select and consume their preferred treatment (say, three or four glucose tablets) and note exactly how long it takes for their glucose levels to increase >50 mg/dL. If needed, PWD are encouraged to repeat this experiment at other times and with several different treatment options until they find at least one that works well for them. With this practice, PWD can begin to trust that glucose levels will indeed rise after treatment. This practice will also assist them in estimating the amount of time they will have to tolerate the discomfort of hypoglycemia. It can also help worried individuals see that consuming larger and larger portions of carbohydrates does not make their glucose levels rise any faster.

As a next step, once PWD feel courageous enough to begin using their identified treatment at the time of actual hypoglycemic events, they may need help in planning strategies to feel safe during the post-treatment period until their glucose has risen to a safe level. Maddie, for example, in the course of treatment, began once again to experience mild hypoglycemia, as was expected. During those first few events, after consuming her preferred carbohydrate snack, she was able to manage her immediate anxiety by having her husband keep her company during the 20-minute period while she waited for her glucose level to rise.

4. Initiate Graduated Behavioral Exposure.

At the heart of almost all successful treatments for fear and anxiety, including PTSD, is a slow but steady return to the feared activity. This return must not be done too quickly or before equipping PWD with needed resources. Behaviors to be targeted might include adopting appropriate medication use, returning to physical activity, reducing dependence on glucose tablets, or cutting back on overeating before bedtime. In almost all cases, the focus is on enhancing PWD’s ability to safely tolerate lower glucose levels and to gain a sense of confidence that hypoglycemic events can be avoided or addressed effectively (46,48).

Fred agreed to start by walking to the end of his block each morning with his wife. After several mornings, he felt confident enough to move to the next stage— walking two blocks, and then three. Gradually, his walking distance and time expanded, and he began to walk alone. Soon thereafter, he was able to return to trail running. As his confidence expanded, he moved on to the next set of challenging tasks, which involved slowly increasing his premeal insulin boluses.

Conclusion

High levels of hypoglycemic fear are common in adults with type 1 or type 2 diabetes. When such fear looms so large that individuals begin to limit their lives and/or keep their glucose levels dangerously high, we refer to this as HFsyn. At the core of HFsyn is a loss of confidence in one’s body—a sense that individuals feel they can no longer trust their own bodies and/or their own abilities to respond effectively to keep them safe while sleeping, driving, exercising, or taking part in social situations.

To escape this trap, two groups of effective strategies have been described. First, for those who are at heightened risk of severe hypoglycemia, there are six key BE SAFE strategies: optimizing medications, being prepared to treat hypoglycemia appropriately, adopting appropriate diabetes technology, addressing IAH, deciding on a no-delay glucose value for treatment, and identifying and addressing times of excessive risk. In our clinical experience, we find that BE SAFE strategies are rarely sufficient for reducing excessive hypoglycemic fear, and, in some cases, they may not even be necessary for many PWD with HFsyn. Thus, we also described a second group of interventions, the four FEEL SAFE strategies: adopting appropriate diabetes technology (which is also a BE SAFE strategy), learning to discriminate symptoms, practicing hypoglycemia treatment, and introducing graduated behavioral exposure.

We are not suggesting that all BE SAFE and FEEL SAFE strategies will be needed in all HFsyn cases. Care should be individualized for each person. Depending on the case, the skilled interventionist, who we suggest should most likely be a specially trained diabetes nurse educator or mental health professional, will need to select the most appropriate group of strategies. In addition, it must be acknowledged that these 10 strategies may be insufficient for a subset of PWD with HFsyn, especially when there are deep-rooted core beliefs and/or an underlying, pervasive anxiety disorder that make it all but impossible for someone to tolerate the uncomfortable feelings that are likely to arise in the course of treatment, and especially during graduated behavioral exposure. In such cases, the first step should be referral to an anxiety disorder specialist who can provide appropriate treatment. Subsequently, BE SAFE and FEEL SAFE strategies may then prove to be useful.