Navigating Hypoglycemia in Diabetes Care: Clinical Management Strategies and Glucagon Treatment Options
EXECUTIVE SUMMARY
Hypoglycemia, defined as a blood glucose level less than 70 mg/dL, can be life-threatening, particularly with insulin therapy, and imposes a significant risk factor leading to severe morbidity and increased medical costs.
- A recent global study people with diabetes on insulin therapy revealed that four of five individuals with type 1 diabetes and about one-half of individuals with type 2 diabetes reported a hypoglycemic event at least once every four weeks.
- It is estimated that 25% to 40% of people with type 1 diabetes and 6% to 17% of people with type 2 diabetes have impaired awareness of hypoglycemia, resulting in a diminished ability to recognize hypoglycemic events, which can lead to inadequate intervention and treatment.
- Multiple glucagon kits are available for treatment, and the characteristics of these agents are described in detail.
- Technology approaches include using continuous glucose monitoring devices, which have become increasingly available for patients.
Hypoglycemia is a life-threatening complication of diabetes mellitus treatment, particularly insulin therapy. It not only disrupts patients’ quality of life but also imposes significant economic burdens caused by emergency department visits or possible hospital admissions.
Hypoglycemia, in general, is defined as a blood glucose level < 70 mg/dL (3.9 mmol/L). As a preventable and potentially acute complication of diabetes management, providing proper patient education, identifying key risk factors, and tailoring treatment approaches are crucial for prevention.
This review aims to elucidate the common causes of hypoglycemia, identify significant risk factors, and compare available pharmacological options, such as various forms of glucagon devices and outpatient clinical management strategies, to address and prevent hypoglycemic episodes. Additionally, this article delves into the public health implications of hypoglycemia and its effect on the healthcare system. Finally, a clinical case is presented to bridge the knowledge gap by incorporating the newest American Diabetes Association Standards of Care in Diabetes on this topic and the key concepts discussed in this review.
Introduction: Epidemiology and Economic Implications — The Public Health Aspect
Severe hypoglycemia is a life-threatening complication that most commonly occurs in those with diabetes secondary to pharmacotherapeutic treatment, especially when using insulin therapy. Other etiologies may include, but are not limited to, alcohol use, critical illness, and counterregulatory hormone deficiencies in people without diabetes. Therefore, hypoglycemia is considered a significant risk factor leading to severe morbidity and mortality.
According to the National Diabetes Statistics Report, 2020 Estimates of Diabetes and Its Burden in the United States, there were 9.6 emergency department (ED) visits per 1,000 adults with diabetes (95% confidence interval [CI], 8.9 to 10.3) in 2018.1 Of all the hypoglycemia-related ED visits in 2018 among U.S. adults, the mortality rate was < 0.1%; 23.1% were admitted to the hospital for observations and 70.1% were managed and discharged.1
In a recent study published in 2021, Bajpai et al found that the median cost of hospitalization associated with severe hypoglycemia was $11,988.80 ($3,728.90 to $33,192.20; 25th to 75th interquartile range).2 Economic consequences of diabetes-related hypoglycemia events can affect those involved in diabetes care, from patients to family, caregivers, and employers, leading to an increased need for diabetes supplies or clinical appointments.3
Frequent hypoglycemic events would increase the psychological burden for people with diabetes, their families, and healthcare professionals. Therapeutic inertia, such as not initiating or titrating insulin therapy, often occurs because of the fear of possible hypoglycemia.4
In type 1 diabetes (T1D), the fear of hypoglycemia in patients is universal.5 Although hypoglycemia episodes happen less frequently in type 2 diabetes (T2D), the occurrence still is significant because of the larger population of T2D patients; this makes hypoglycemia a concern in T2D management.6-8
Hypoglycemic episodes can be prevented through optimal diabetes management and education. Advanced insulin therapy options (i.e., insulin analogs, concentrated insulins), glucagon products, and state-of-the-art diabetes technologies (i.e., continuous glucose monitoring [CGM] devices and hybrid closed-loop insulin pump systems) have offered a layer of protection in preventing hypoglycemia-associated hospitalizations in those who use or rely on daily insulin therapy.
Parents of children with T1D, for example, feel relief after their children are started on a CGM and an insulin pump — a hybrid closed-loop system — minimizing their constant fear that their children might experience hypoglycemia episodes overnight while sleeping.9
The landmark trials in diabetes management, e.g., Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease (ADVANCE), and Veterans Affairs Diabetes Trial (VADT), have shown increased mortality and morbidity caused by hypoglycemia — raising the risk of ischemia and arrhythmias and leading to neurological damages — as a result of intensive glycemic management.10-12
Although hypoglycemia episodes have caused unscheduled medical visits and negative health consequences, leading to unnecessary or preventable medical costs, further discussions on this topic are warranted to potentially reduce its negative effect on patients and the healthcare system at large.
Discussing Hypoglycemia: A Multidimensional Approach
Biological Factors
A global study including people with diabetes and on insulin therapy revealed that four of five individuals with T1D and about one-half of individuals with T2D reported a hypoglycemic event at least once every four weeks.13,14 Although most hypoglycemic episodes are iatrogenic, these episodes also can occur in individuals without diabetes.
During an episode of hypoglycemia in otherwise healthy people, there is a sequence of counterregulatory hormones, such as epinephrine, cortisol, and glucagon, to regulate blood glucose levels. The pancreatic beta cells respond by suppressing insulin release, and pancreatic alpha cells increase glucagon secretion. The sympathetic-adrenal response includes increased adrenaline, norepinephrine, adrenocorticotropic hormone (ACTH), and glucocorticoids.
In individuals with diabetes, this response is impaired. People with diabetes who are treated with exogenous insulin or insulin secretagogues for glycemic management have an increased risk of hypoglycemia because of an increased level of insulin in the body. The severity of hypoglycemic episodes may vary and involve two types of symptoms, e.g., neurogenic and neuroglycopenic.
Neurogenic symptoms involve shakiness, anxiety, nervousness, palpitations, diaphoresis, dry mouth, pallor, and pupil dilation. In contrast, neuroglycopenic symptoms occur because of a lack of neuronal glucose, causing altered mental status, confusion, ataxia, paresthesia, headache, seizures, coma, or even brain death.15
Impaired awareness of hypoglycemia (IAH) or hypoglycemia unawareness is defined as the diminished ability to recognize hypoglycemic events, leading to treatment failure within the opportune time period.16 Twenty-five percent to 40% of people with T1D and 6% to 17% of people with T2D are estimated to have IAH.16
Although people with T1D already have a loss of counterregulatory mechanisms, IAH and impaired adrenomedullary responses further contribute to the risk of hypoglycemia.16 People with IAH also are at a sixfold increased risk of developing level 3 hypoglycemia (discussed in a subsequent section).17
The hallmark symptoms of IAH include the loss of sympathetic symptoms such as palpitations, tremors, anxiety, and epinephrine responses. Autonomic dysfunction and hypoglycemia unawareness can lead to an increased risk of cardiovascular events and mortality.18
People with T1D may be at risk for “dead in bed” syndrome.18 This syndrome describes cases of unexplained death seen in people with T1D younger than 50 years of age. Proposed explanations include possible severe hypoglycemia, hypoglycemia unawareness, or cardiac arrhythmia.18
Exposure to repeated moderate levels of hypoglycemia may lead the person to an increased tolerance of low blood glucose levels (adaptation), thus causing reduced recognition and defense mechanisms to prevent the episodes (hypoglycemia unawareness).
In the effort to enhance the prevention and detection at the population level, two validated educational programs — Blood Glucose Awareness Training (BGAT) and Hypoglycemia Anticipation, Awareness, and Treatment Training (HAATT) — were designed for this purpose. While BGAT educates individuals with diabetes to recognize the early signs of hypoglycemia and hyperglycemia and take appropriate actions to manage these conditions, HAATT is specifically developed to help people with diabetes minimize their risk for hypoglycemia.19
Hypoglycemia typically presents with shakiness, dizziness, and/or confusion; in a paradoxical condition known as pseudohypoglycemia, these symptoms appear even when blood glucose levels are above the standard threshold. Pseudohypoglycemia is defined as a condition where the measured blood glucose levels are above 70 mg/dL (> 3.9 mmol/L) but the person still exhibits classic hypoglycemic symptoms.20
In people without diabetes, hypoglycemia can occur postprandially (reactive hypoglycemia). Within four hours after food consumption, reactive hypoglycemia can occur and can be identified by Whipple’s triad.15 Postabsorptive hypoglycemia is a fast state that can occur during an overnight fast, between meals, or after exercise.15
Other factors, such as alcohol use, critical illnesses, sepsis, and end-stage liver or kidney disease, can contribute to postabsorptive hypoglycemia.15
Pharmacotherapeutic Options for Hypoglycemia Management
For several decades, lyophilized glucagon injections were used as the principal strategy for managing severe hypoglycemia episodes. Amphastar is the only pharmaceutical company that still makes the traditional glucagon kit. However, challenges in preparing and administering traditional glucagon kits have paved the way for improved and user-friendly glucagon formulations.
• Baqsimi, a dry nasal powder form of glucagon administered via a prefilled device, holds a single, fixed, ready-to-use dose that may be used in patients ages 4 years and older.21 In June 2023, Baqsimi was acquired from its original manufacturer.22
• Gvoke is available as an autoinjector or prefilled syringe and does not require reconstitution. This product can be administered to patients ages 2 years and older.23 The first version, the original prefilled syringe, has been discontinued.24
• Dasiglucagon, under the trade name Zegalogue, is a glucagon analog available as an autoinjector or a prefilled syringe for patients 6 years of age and older.25
For this review article, the focus is to describe the various innovative forms of glucagon devices available for treating hypoglycemia. Table 1 summarizes the details of each of the new forms of glucagon devices.
Table 1. FDA-Approved Glucagon Products |
||||
Types of Glucagon Products |
||||
Baqsimi (glucagon nasal spray)21 |
Gvoke HypoPen (glucagon injection)23 |
Zegalogue (dasiglucagon)25 |
Glucagon |
|
Manufacturer |
Eli Lilly and Company |
Xeris Pharmaceuticals, Inc. |
Zealand Pharma A/S |
Amphastar Pharmaceuticals, Inc. |
FDA Approval |
July 2019 |
August 2021 (autoinjector) |
March 2021 |
December 2020 |
Type of Device |
|
|
|
|
Reconstitution? |
No |
No |
No |
Yes |
Age |
≥ 4 years of age |
≥ 2 years of age |
≥ 6 years of age |
No age restriction |
Site of Administration |
Nasal |
SQ injection to the upper arm, outer thigh, or lower abdomen |
SQ injection to the upper arm, outer thigh, or lower abdomen |
IM or SQ |
Dosage |
Age ≥ 4 years:
|
Adult
Pediatric Children ≥ 12 years of age:
Children 2 to 12 years of age:
|
|
Adult
Pediatric
|
Onset of Action |
~15 minutes27 |
~10-15 minutes |
10 minutes (median time for plasma glucose recovery) —adults |
Dose-dependent: |
Peak Effect |
Children ≥ 4 years of age: ~60 minutes21 |
50 minutes |
7 to 17 years of age: ~21 minutes; |
Route dependent: |
Duration of Action (measure glucose elevation) |
> 90 minutes (patients with type 1 diabetes)27 |
> 90 minutes (patients with type 1 diabetes)23 |
N/A |
Dose-dependent: |
Effects on Plasma Glucose |
3-5 minutes slower response compared to IM administration |
10 minutes onset, delayed by a few minutes in comparison to Glucagon Emergency |
9-14 minutes: increased plasma glucose by 6-10 minutes increased plasma glucose to |
|
Median Average Wholesale Price |
$337 per dose |
$368 per dose |
$371 per dose |
$266 per dose |
Special Considerations |
Check for clear and water-like consistency; reconstituted solution should be inspected for particulate matter and discoloration before administration. |
|||
Side Effects |
|
|
|
|
FDA: Food and Drug Administration; SQ: subcutaneous; IV: intravenous; IM: intramuscular |
||||
Mechanism of Action: Glucagon and Dasiglucagon
Glucagon promotes gluconeogenesis and hepatic glycogenolysis, which, in turn, leads to an increase in glucose concentration in the bloodstream. This process requires hepatic glycogen storage to resolve a hypoglycemic episode after injection or inhalation of glucagon.
Dasiglucagon, on the other hand, is a glucagon receptor agonist that activates hepatic glucagon receptors, which stimulates gluconeogenesis and glycogenolysis in the liver.25 To exert its effects, dasiglucagon depends on glycogen storage in the liver.
Clinical Evidence
The clinical effect of these agents is discussed in the following section, focusing on the safety and efficacy demonstrated in the selected clinical trials.
Glucagon Trials: Exercise-Induced Hypoglycemia
A clinical trial using a mini-dose glucagon (MDG) strategy in individuals with T1D has demonstrated the agent’s efficacy in preventing exercise-induced hypoglycemia and reduced the likelihood of resulting in post-intervention hyperglycemia (compared to carbohydrate consumption).29
In addition, another clinical trial with ready-to-use liquid stable glucagon (RTUG) demonstrated that a fixed dose of this agent was able to prevent exercise-induced hypoglycemia during aerobic exercise by maintaining individuals with T1D at their euglycemic state.30 Similarly, RTUG also was shown to be less likely to cause post-intervention hyperglycemia compared to ingestion of carbohydrates.
Dasiglucagon Trials: The Next-Generation Glucagon Analog
A Phase III clinical trial with ready-to-use, aqueous dasiglucagon, including adults with T1D, showed that this agent, exhibiting a similar safety profile compared to reconstituted glucagon, reliably corrected severe hypoglycemia episodes in participants.31
Additionally, another trial in children and adolescents with T1D demonstrated similar efficacy and safety outcomes of dasiglucagon in correcting insulin-induced hypoglycemia episodes.32
Clinical Principles
Hypoglycemia is a critical limiting factor in managing T1D and T2D. Hence, an assessment of the risk of hypoglycemia by a clinician is recommended at every visit with patients treated with insulin and insulin secretagogues, followed by patient education on measures that could prevent hypoglycemia episodes.28 Common strategies to avoid episodes of hypoglycemia include using blood glucose monitoring (BGM) or CGM, frequent snacks and meals, and the possible use of continuous subcutaneous insulin infusion. For patients with hypoglycemia unawareness, training programs such as BGAT, HypoAware, Dose Adjusted for Normal Eating (DAFNE), and DAFNEplus may help patients recognize and prevent hypoglycemia effectively.33
Symptoms of hypoglycemia include shakiness, irritability, confusion, tachycardia, and hunger.28 (See Table 2.)
Table 2. Hypoglycemia Risk Factors and Symptoms |
Risk Factors |
|
Symptoms |
|
Clinically, hypoglycemia is classified into three levels. Level 1 hypoglycemia is defined as a blood glucose level < 70 mg/dL (3.9 mmol/L) and ≥ 54 mg/dL (3.0 mmol/L); level 2 hypoglycemia is defined as a blood glucose level < 54 mg/dL (3.0 mmol/L) and is the threshold at which neurological symptoms begin to occur and requires immediate glucose treatment; and level 3 hypoglycemia, which is a severe event characterized by altered mental and/or physical status requiring immediate assistance for treatment of hypoglycemia.28 Glucagon should be prescribed for all patients using insulin therapy or at a higher risk for hypoglycemia.28
Patients should be educated on the risk factors for hypoglycemia, which include fasting for laboratory tests or procedures, delayed meals, alcohol consumption, intense exercise, and long duration of sleep. Insufficient understanding of their insulin therapy or instructions or mistaking short-acting insulin for long-acting insulin could further increase a patient’s risk for frequent hypoglycemia episodes. Patients need to be educated about the usage of CGM. Caregivers should be educated on the signs and symptoms of hypoglycemia, the correct usage of glucagon devices, and the importance of vigilant cognitive function evaluations to assist patients in treating hypoglycemic events.
Technology to Detect and Prevent Hypoglycemia
Adults using intensive insulin therapies (multiple daily injections [MDI] or insulin pump therapy) and youths with T1D or T2D using intensive insulin therapies should be encouraged to use BGM (and/or CGM) to assess their glucose levels before meals and snacks, at bedtime, occasionally postprandially, before exercise, when they suspect low blood glucose, and after treating low blood glucose, as well as before performing critical tasks such as driving.34 In recent years, multiple randomized controlled clinical trials have shown that CGM devices can better reach A1c targets while minimizing hypoglycemic episodes.35,36
CGM devices can be divided into three categories: real-time CGM (rtCGM), intermittently scanned CGM (isCGM) with and without alarms, and professional CGM. (See Table 3.)
Table 3. Types of Continuous Glucose Monitoring Devices |
|
Real-time CGM |
|
Intermittently Scanned CGM |
|
Professional CGM |
|
CGM: continuous glucose monitoring |
|
• The rtCGM devices measure and store glucose levels continuously without prompting.
• The isCGM devices with and without alarms measures glucose levels continuously but require scanning to store glucose values. isCGM devices should be scanned at least once every eight hours.35,36
• Professional CGMs are clinic-based devices that provide blinded or unblinded data for a discrete period.
The rtCGM or isCGM devices should be offered to patients who can use devices safely (either by themselves or with a caregiver), and the device should be chosen based on patient desires, circumstances, and needs.35,36 Two specific devices, FreeStyle Libre 2 (isCGM) and Dexcom G6 (rtCGM), have been designated by the U.S. Food and Drug Administration (FDA) as integrated CGM (iCGM) devices so they can be reliably integrated with other digitally connected devices, including automated insulin-dosing systems.37
An automated insulin delivery system (AID), also known as an artificial pancreas, adjusts insulin delivery based on sensor-derived glucose levels, which may facilitate better glycemic management and lower the risk of exercise-induced hypoglycemia.
In August 2020, the FDA approved the MiniMed 770G insulin pump system that automatically adjusts background insulin every five minutes with little or no input from the user.38,39
Using real-time glucose readings, the system can calculate a personalized amount of insulin to be delivered and connects directly with a compatible smartphone to allow easy viewing of glucose trends and insulin delivery.38,39 Two multicenter, randomized controlled trials have shown that another AID system (t:slim X2 insulin pump with Control-IQ Technology, approved in 2019) provides significantly better glycemic management (within the target range of 70 mg/dL to 180 mg/dL) for a more significant percentage of time than a sensor-augmented insulin pump in both children and adults with T1D.40,41
Continuous research, specifically in the technology space, is being conducted to increase the safety of glycemia management — thus reducing the risk of hypoglycemia — through a multimodal approach.
Closing the Gaps: Putting it All Together
Managing hypoglycemia and preventing subsequent episodes involves assessing risk factors and tailoring treatment strategies to mitigate the risk.
A Clinical Vignette: Frequent Hypoglycemia Episodes
Patient Information
Name: Nick
Age: 20
Gender: Male
Medical History:
• Type 1 diabetes mellitus (diagnosed 12 years ago)
• Crohn’s disease (diagnosed five years ago)
• Hypothyroidism (diagnosed three years ago)
• Asthma (diagnosed one year ago)
Current Medications
• Insulin degludec (Tresiba): 24 units daily before bedtime
• Insulin lispro-aabc (Lyumjev): 1 unit per 15 g of carbohydrates before each meal and snack
• Levothyroxine: 88 mcg, one tablet by mouth daily in the morning 30 minutes before breakfast
• Budesonide/formoterol (Symbicort): 80/4.5 mcg, two puffs by mouth twice daily
• Albuterol HFA: 90 mcg, two puffs by mouth every four to six hours as needed for wheezing or shortness of breath
Chief Complaint
“I think I am doing something wrong because I keep having low blood sugar,” Nick says.
Presenting History
Nick, a 20-year-old male with a history of T1D, presents at the clinic complaining of frequent hypoglycemia episodes that often have caused him to panic. He describes some episodes of confusion for moments and feels like it was a blur sometimes. Fortunately, his roommate helped him to bring his blood glucose up while he was experiencing hypoglycemic episodes.
The patient mentions the fatigue he felt after recovering from an episode and the mentally draining aspect of managing low blood glucose levels.
At the time of his visit, his glucose report downloads showed some large glucose variability (as low as the 30s to as high as the 340s), with an average of three fingersticks per day. He explains that sometimes he does not check his glucose before eating and “guesstimates” because his fingers are sore.
Past Medical History
Nick was living at home before moving out for college. Before college, he often ate home-prepared meals, simplifying his carbohydrate counting and mealtime insulin dosing.
However, after moving out, his glucose had shown significantly large variability as the result of eating out more often rather than preparing food at home. Occasionally, he would use an additional injection to correct his high glucose level regardless of meals.
Because of the recent frequent hypoglycemic episodes that he experienced, he had increased concerns about them occurring when no one was around to rescue him.
Whenever his glucose is low, he uses fast-acting sugars that he has available, which usually are candy bars. The lows tend to occur a couple of hours after physical activity. He plays an intense, high-impact sport at college and worries about managing these lows.
Social History
Occupation: College student who works at a coffee shop on weekends
Smoking: Never
Recreational drugs: Never
Alcohol: Occasionally during college parties
Assessment
After reviewing his insulin injections, insulin doses were adjusted to match his changed lifestyle. Because of his intense physical activity and frequent hypoglycemic episodes (as low as the 30s), having a glucagon product is necessary since it can be lifesaving. The product preference depends on the insurance formulary and whether the patient prefers a nasal or injectable version.
The American Diabetes Association Standards of Care 2024 provides a comprehensive list of factors increasing the risk of hypoglycemia, supporting the assessment of hypoglycemia risk (one of which states “history of severe hypoglycemia event”).28
During the encounter, the care team assessed Nick’s risk and discussed with him when to use correctional insulin doses and how much to bolus before meals to minimize the risks of hypoglycemia, especially before physical activity.
Recommendations on Prevention, Treatment, and Management
Pharmacotherapeutic Approach
According to the American Diabetes Association Standards of Care Recommendation 6.13, glucagon should be included in the management plan for those taking insulin or at a higher risk of hypoglycemia.28 In addition, glucagon administration is not limited to only healthcare professionals; thus, these individuals’ support systems also should learn about glucagon injection.
With frequent hypoglycemia episodes as low as the 30s, Nick will need to be prescribed glucagon (with a preference for preparations that do not require reconstitution), and education on the glucagon device will be given to people around him, especially the group who engages in the high-impact sport with him.28
Diabetes Technology Approach
According to the American Diabetes Association Standards of Care Recommendation 7.14, adults with diabetes who take MDI or have an insulin pump (continuous subcutaneous insulin infusion) are recommended to be on a CGM.42 The CGM can be real-time or intermittently scanned, depending on the individual’s preference, situation, and needs. This recommendation fits Nick’s situation, since he is taking at least three insulin injections daily.
Along the same line, the American Diabetes Association Standards of Care Recommendation 7.25 states that for diabetes management in adults with T1D and taking MDI, insulin pump therapy should be considered with or without sensor-
augmented, low-glucose-suspend feature and/or automated insulin delivery (hybrid closed-loop) system.42
With the system of CGM and insulin pump, Nick will be able to adjust his insulin infusion before engaging in physical activity and have the system monitor his glucose levels, thus reducing the risk of hypoglycemia by catching the downward trend before he experiences an episode.
Diabetes Education Approach
Reducing hypoglycemia is one of the many benefits associated with diabetes self-management education and support.42 (See Primary Care Reports, August 2021.) The goal of engaging Nick in diabetes education is to devise a plan for hypoglycemia prevention and hypoglycemia management involving people around him (because he has a history of experiencing severe hypoglycemia). Since individuals with T1D have variable glycemic responses to physical activity, it would be beneficial for Nick to consult with a clinical exercise physiologist to reduce
exercise-induced hypoglycemia.
Summary and Take-Home Points
Hypoglycemia episodes can be life-threatening. Preventing these episodes is a continuous effort where diabetes technology for glucose monitoring meets the individual’s behavioral modifications and assessment.
Effective hypoglycemia management, especially severe hypoglycemia, involves timely administration of glucagon when warranted and assistance from people around the individual who is experiencing hypoglycemia.
Conclusion
Identifying individual risk factors, customizing treatment plans, and educating patients on the use of glucagon devices are critical steps in enhancing hypoglycemia management. These collaborative efforts between patients and healthcare professionals enable more effective hypoglycemia management, often leading to stable blood glucose levels within a short timeframe. Such strategies not only alleviate patients' fear of hypoglycemic episodes but also decrease the frequency of ED visits and related healthcare costs. Although traditional glucagon emergency kits continue to play a vital role, the introduction of newer pharmacotherapeutic options has significantly improved ease of use and convenience.
Through focused patient education and the provision of accessible treatment options, healthcare professionals and patients can work together toward achieving safer glycemic management, thereby improving patient quality of life and diminishing the overall effect on the healthcare system.
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Hypoglycemia, defined as a blood glucose level less than 70 mg/dL, can be life-threatening, particularly with insulin therapy, and imposes a significant risk factor leading to severe morbidity and increased medical costs. As a preventable and potentially acute complication of diabetes management, providing proper patient education, identifying key risk factors, and tailoring treatment approaches are crucial for prevention.
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