Abstract
Insulin use is a major risk factor for developing hypoglycemia (Table 1). In 2022, Myers et al indicated 6.8% of people with type 1 diabetes (T1D) and 3.7% of people with type 2 diabetes (T2D) reported having a severe hypoglycemic event requiring emergency medical services (EMS). Furthermore, Hughes et al surveyed members of the T1D Exchange Registry in 2020, and among them, mild (level 1) hypoglycemic events averaged 7.4 per week, moderate (level 2) hypoglycemic events averaged 5.0 per week, and severe (level 3) hypoglycemic events averaged 0.07 per week (3.6/52 wk).
Definitions for Levels of Hypoglycemia.
These data indicate severe hypoglycemic events are rare; however, one severe hypoglycemic event can be life-threatening. Predicting which mild or moderate hypoglycemic event will escalate to a severe hypoglycemic event is challenging. Consider, too, that these events could be especially problematic for children and older adults, who may not be able to effectively recognize and/or communicate to caregivers that they are experiencing hypoglycemia.
The transition of care for people with diabetes is a critical period that poses challenges with glycemic management. Hypoglycemia is a prevalent complication during these transitions, and it is important to ensure safe and effective prevention and treatment. Several strategies could be considered to address the multifaceted nature of hypoglycemia during care transitions. This article aims to identify risk factors and summarize strategies to mitigate this risk.
Risk Factors and Consequences for Hypoglycemia
Besides insulin—assuming correct insulin type, dose, and administration—other factors are associated with high risk for hypoglycemia; these include impaired awareness of hypoglycemia and social determinants of health (Table 2).
Risk Factors for Hypoglycemia in People With Diabetes.
People with diabetes may simultaneously have more than one risk factor, thereby placing them at increased risk for hypoglycemia. For example, people with T1D may have long-standing diabetes and impaired awareness of hypoglycemia, and people with T2D may be receiving a sulfonylurea, have had a cardiovascular event, have autonomic neuropathy, and be affected by social determinants of health, such as poor access to health care resources and/or healthy foods.
The consequences people with diabetes may face after a severe hypoglycemic event include (1) poor next-day functioning; (2) EMS use, emergency department (ED) visit, and/or hospitalization; (3) death; and (4) fear of future hypoglycemia.
Next-day functioning may be affected by overnight glucose concentrations, according to Pyatak et al. Overnight glycemic variability—possibly due to disrupted sleep with awakening to and addressing frequent continuous glucose monitoring device alarms for hyperglycemia and hypoglycemia—was predictive for overall next-day functioning, including poorer sustained attention and lower engagement in demanding daily activities.
Snoek et al reported that among people with diabetes and unrelated caregivers, 20% said they used a health care resource, such as calling for an ambulance, calling their health care provider (HCP), and going to the ED, because of a severe hypoglycemic event. Furthermore, approximately 40% of those that arrived at the ED indicated a subsequent overnight hospital stay for themselves or for those in their care. Additionally, during the last severe hypoglycemic event, over 70% felt scared, and over 40% felt unprepared or helpless.
For some risk factors and consequences for severe hypoglycemia, discerning which came first—the chicken or the egg—may be difficult. First, cognitive impairment and dementia are associated with poor diabetes self-management and frequent severe hypoglycemic events; however, frequent severe hypoglycemic events may contribute to cognitive impairment and dementia. Second, impaired awareness of hypoglycemia is associated with frequent hypoglycemic events due to blunted hypoglycemia symptoms until the glucose reaches potentially dangerously low levels. For example, people with hypoglycemia unawareness may not recognize hypoglycemia symptoms until they reach level 2 or level 3 hypoglycemia. Yet the more frequently hypoglycemic events happen, the worse impaired awareness of hypoglycemia becomes, until the person has hypoglycemia unawareness. Third, Standl et al reported that among people with T2D, nearly the same number of them had a cardiovascular event (eg, fatal and nonfatal myocardial infarction, stroke) that preceded a severe hypoglycemic event and vice versa.
Fear of hypoglycemia can be so overwhelming to both people with diabetes and their caregivers that those with diabetes limit their activities and allow their glucose levels to run high as a preventive measure. According to Polonsky et al, a previous severe hypoglycemic event is a major contributor to fear of hypoglycemia, and affected people may have difficulty accurately perceiving body sensations as those truly associated with hypoglycemia rather than associated with another cause or with normal physiology. Yet people with diabetes and their caregivers can be prepared—and thereby counter their feelings of unpreparedness or helplessness and thus their fear—to treat for severe hypoglycemia.
Before a person develops hypoglycemia, Polonsky et al also suggest a person with diabetes establish a no-delay treatment glucose threshold. This is a glucose level in which a person will always treat themselves for hypoglycemia, including when they do not yet have hypoglycemia symptoms, by using the 15-15 rule (15 g of carbohydrates, wait 15 minutes, and check glucose; then repeat every 15 minutes until glucose attains >70 mg/dL; Table 3). Maybe the last time when they had hypoglycemia symptoms, their glucose level rapidly increased after eating 15 g of carbohydrates, and symptoms rapidly abated. Then, when they encounter a glucose level similar to the last time, they may rationalize their glucose level may not be that bad yet—considering the previous outcome—and choose to wait to treat. Yet with waiting, their glucose may precipitously drop and not normalize with eating 15 g of carbohydrates, leading to a severe hypoglycemic event.
Common Hypoglycemia Scenarios and Proposed Management Approaches
Abbreviations: CGM, continuous glucose monitoring; EMS, emergency medical services.
People with impaired awareness of hypoglycemia may benefit from short-term relaxation of glycemic goals to reestablish awareness of hypoglycemia.
A person may quickly progress from level 1 to level 2 to level 3 hypoglycemia regardless of whether they consumed 15 or more grams of carbohydrates. Thus, prepositioning fast-acting carbohydrates of the person's choice and ready-to-use glucagon is important such that they are easily accessible to the affected person and their caregivers when needed.
Guidelines for Treatment of Hypoglycemia
The guidelines from the American Diabetes Association (ADA), the Endocrine Society, the American Association of Clinical Endocrinology, the International Society for Pediatric and Adolescent Diabetes, and the American Society of Consultant Pharmacists are aligned in the recommendation for glucagon prescribing for those, across all ages, at increased risk for level 2 or level 3 hypoglycemia. The 2024 ADA Standards of Care align with the 2023 Endocrine Society's guidelines for preferring ready-to-use glucagon rather than glucagon preparations that require reconstitution (ie, traditional lyophilized glucagon in a glucagon emergency kit; Table 4). Both the standards and the guidelines stress the use of ready-to-use glucagon because untrained family members, friends, coworkers, teachers, and so on will often be the ones administering the glucagon during a hypoglycemia emergency (ie, level 3 hypoglycemia).
Characteristics of Currently Available Ready-to-Use Glucagon Formulations
Abbreviations: AI, autoinjector; PFS, prefilled syringe; SC, subcutaneous.
Lilly divested Baqsimi to Amphastar Pharmaceuticals, Inc (April 2023).
Gvoke HypoPen (AI), Gvoke PFS, and Gvoke kit are from Xeris Pharmaceuticals, Inc.
Novo Nordisk has an agreement with Zealand Pharma to commercialize Zegalogue (September 2022).
Unfortunately, glucagon prescribing to date remains low, as evidenced in a 2023 Herges et al study, despite the availability of ready-to-use glucagon formulations since as early as 2019. Pharmacist prescribing of glucagon to those identified as high risk may be one approach to increase glucagon prescribing. Whitfield et al reported in 2022 success—more glucagon prescribing—with a pharmacist-led outreach intervention to HCPs before patients' appointments in a North Carolina academic health care system. Coincidentally, in 2021 and updated in 2023, North Carolina authorized "immunizing pharmacists practicing pharmacy in the state of North Carolina and licensed by the North Carolina Board of Pharmacy to dispense, deliver, or administer glucagon as directed" for those the pharmacists have identified to be at risk for hypoglycemia and educating about the available treatments. Recommending glucagon can also be a role for diabetes care and education specialists (DCESs) to address the current gap in care.
Hypoglycemia During Care Transitions
The 2022 National Standards for Diabetes Self-Management Education and Support (DSMES) encourage HCPs to refer people with diabetes for DSMES—and consider engaging a DCES—at 4 critical times: (1) at diagnosis, (2) annually or when not meeting treatment targets, (3) when complications develop (eg, medical, physical, psychosocial complications), and (4) at transitions in life or care.
During care transitions, people with diabetes may be more susceptible to suffering severe hypoglycemic events. In any transition, the handoff for care may be suboptimal, thereby possibly leading to poor diabetes management and higher risk for severe hypoglycemia. For example, a person's insulin dose may have been lowered due to a severe hypoglycemia event that required hospitalization; however, they may not have received written discharge instructions about the dose reduction and resumed their prehospitalization regimen after returning home. Additionally, a ready-to-use glucagon dosage form may have been prescribed at the time of hospital discharge; however, the outpatient HCP may have been unaware of the glucagon prescription and therefore did not follow up about whether the prescription was filled.
However, even with an optimal handoff between HCPs, care transitions can still be suboptimal due to person-related factors. For example, Majidi et al reported that some college students may not reliably receive ambulatory diabetes care due to irregular schedules, lack of parental involvement, and finances.
Care transitions for people with diabetes may include transitions between care settings, life stages, or HCPs (Table 5). Here we discuss each of these 3 care transitions and considerations related to hypoglycemia risk.
Examples of Care Transitions Between Care Settings, Life Stages, and Health Care Providers.
Care Setting-Related Transitions
Particularly high-risk periods for hypoglycemic events are between hospital discharge and admission to a postacute or long-term care (LTC) facility and between hospital discharge and return home. Munshi et al reported that nearly one-third of residents (across 6 LTC facilities in the northeastern United States) who had at least 1 hypoglycemic event had their event within 2 weeks of LTC facility admission. Furthermore, Bhalodkar et al indicated that by 30 days after a first hospital admission, 19% of people with diabetes (mean age, 56 years; SD, 13 years) returned to the ED and were rehospitalized. However, in a parallel group of people who at the time of hospital discharge were enrolled in a specialized multidisciplinary diabetes management program—which included a visit with a DCES or nurse practitioner who developed an individualized plan for each person with diabetes—only 7% of people returned to the ED and were rehospitalized, which is a reduction of 171%.
Life-Stage Care Transitions
Transition from childhood to young adulthood is a period in which people with diabetes are particularly vulnerable to severe hypoglycemic events due to normal physiologic changes, psychosocial factors, and increasing reliance on themselves, rather than more reliance on their parents like they did at younger ages, for diabetes care. They are also transitioning from a pediatrician or local primary care provider (PCP) to an adult care provider, possibly one in a faraway town near to where they attend college. During this transition period, specialty care by an endocrinologist either alone or in collaboration with a PCP is recommended; however, Sauder et al identified that only 65% of those with T1D consistently received care from an endocrinologist during this period.
Also, Phan et al reported in the November 2023 issue of ADCES in Practice that among the 27 participating patients ages between 16 and 22 years, only 66% attended the first appointment for transitioning care from a pediatric endocrinologist to an adult endocrinologist. Thereafter, attendance rates precipitously dropped, to 40% for the second care transitions appointment and to 7% for the third (final) care transitions appointment. Phan et al also reported clinic staff did not have a system for automatically rescheduling patients who missed their care transitions appointments; therefore, regardless of the care transition care plan, clinic staff may need to frequently recontact adolescents/young adults to ensure they adhere to their care transition plans.
One resource that may help with care transition for these young persons is the Six Core Elements of Health Care Transition 3.0, created by Got Transition, the federally funded national resource center on health care transition (https://www.gottransition.org/six-core-elements/), for use by clinicians to assist youth and young adults as they transition from a pediatric to an adult-centered model of health care. Available for download is a sample transfer-of-care checklist. The checklist includes various tools, such as a plan of care with transition goals and prioritized actions, a medical summary and an emergency care plan, and a final assessment for transition readiness.
HCP-Related Care Transitions
The handoff of care between HCPs is frequently subpar, and Doyle et al reported that although transfer letters from diabetes specialists often detail results for physical examinations and diagnostic tests, they often lacked treatment plans, future management needs, and expected outcomes. Through use of a templated letter, however, these gaps were addressed, according to Doyle et al.
All templated letters included a current medication list, versus 51% of standard letters; the treatment targets for glycosylated hemoglobin, versus 14% of standard letters; low density lipoprotein, versus 11%; blood pressure, versus 7% of standard letters; the type of diabetes, versus 56% of standard letters; and body weight, versus 44% of standard letters. Most templated letters also included recent blood pressure measurements (98% vs 60%) and whether the person with diabetes had a history of hypoglycemia (80% vs 20%). Therefore, a standard form that everyone in the practice uses can help to ensure critical clinical information, especially the hypoglycemia treatment protocol, is communicated from the referring HCP to the receiving HCP. Such a form may also be useful when care transitions from one HCP to another HCP in the same practice or health care system, which may be the case as care transitions from a pediatrician care provider to an adult care provider. Inclusion of the hypoglycemia treatment protocol will immediately inform the new provider whether the person with diabetes is a candidate for glucagon and whether glucagon has been previously prescribed.
Communication Is Key During Care Transitions
In 2022, Munshi et al proposed a 3-part diabetes management discharge communication plan that could be used for any care transition regardless of care setting or intensity. Each part of the plan is made up of several elements considered to be requisite. There are a total of 6 elements in the plan that pertain to hypoglycemia history and risk. Those 6 elements include the following:
Subsequent care facility and outpatient PCP should receive the date/time for the hypoglycemic events that occurred within the past 7 days, whether hypoglycemia was severe (patient in coma/unconsciousness), list of medications when events occurred, and the explanation(s) for the events.
For each drug: name, administration route, frequency, date/time for the last dose given, and date/time for the next dose to be given; indicate whether patient is using an insulin pump, and if yes, then providing the pump settings.
Recent (past 7 days) changes in glucose-lowering drugs—dose increases/decreases, new drugs, discontinued drugs, rationale for any changes.
Presence of dementia and whether dementia diagnosis was evident before admission.
Assessment for a person's ability for diabetes self-management: clinical documentation (an objective or a subjective narrative) indicating a person's ability to measure and give all drugs prescribed to them and, if prescribed, their ability to self-monitor their glucose.
Assessment for a person's awareness of hypoglycemia: clinical documentation indicating a person's ability level to recognize symptoms for hypoglycemia and readily address through a hypoglycemia treatment protocol.
Proposed Checklist for Facilitating Safe, Successful Care Transitions
Considering the Got Transition resources and the results of the studies by Doyle et al and Munshi et al, we propose this customizable checklist for facilitating a safe and successful care transition (Table 6). The checklist would comprise an overall communication plan for diabetes management and would be shared with all stakeholders, such as the receiving diabetes care team and caregivers, involved in person-centered care.
Customizable Checklist for Incorporating Glucagon Into Diabetes Care Plans for the Safe and Successful Care Transition Between Care Settings, Life Stages, and Health Care Providers
The checklist is derived from the 2024 ADA Standards of Care and guidelines from the Endocrine Society (2023), the American Association of Clinical Endocrinology (2022), the International Society for Pediatric and Adolescent Diabetes (2022), and the American Society of Consultant Pharmacists (2023). Items in the checklist are categorized by stage of the care transition—before, during, and after.
Before the transition, the referring HCP would determine whether the person with diabetes is at high risk for hypoglycemia. Then, they would inform the person and any caregivers about the role of glucagon for hypoglycemia treatment, directions for when and how to use and store it, and its side effects. Also, they would investigate insurance coverage for the various glucagon dosage forms.
Also, before the transition, a hypoglycemia treatment protocol should be developed (Table 7). The protocol could include a no-delay treatment glucose threshold, as Polonsky et al suggest.
Sample Protocol for Hypoglycemia Treatment.
During the transition, the HCP would review the checklist with the person with diabetes, their caregivers, and other diabetes care stakeholders; demonstrate how to administer glucagon; observe the caregiver demonstrating how to administer glucagon; verify the person has a glucagon prescription; and answer any questions.
After the transition, follow-up appointments would be scheduled. During these appointments, the receiving diabetes care team would determine whether the person with diabetes has filled the glucagon prescription; whether glucagon had been administered due to experiencing a severe hypoglycemic event (level 3) and if yes, under what circumstances; and whether refills are available or a new prescription needs to be written.
Conclusion
Transitions of care in health care settings require proactive planning to ensure a person's continuity of diabetes care. Additionally, the person's safety is the top priority during care transitions, with persons with diabetes more susceptible to hypoglycemic events during care transitions. A customizable checklist to encourage appropriate glucagon prescribing and use can be a valuable tool in proactive planning, especially for those with diabetes who are at high risk for hypoglycemia and therefore would benefit from having ready-to-use glucagon.
By using a customizable checklist, the diabetes care team can enhance the person's safety, promote effective communication among care stakeholders, and better contribute to the continuum of diabetes care. Periodic or planned updates and revisions can be made to the checklist, ensuring it includes current, relevant information (eg, including information from the annually updated ADA Standards of Care) for people with diabetes. ■
Footnotes
Acknowledgements
Matthew Krecic, DVM, MS, MBA, Xeris Pharmaceuticals, Inc, provided writing support.
Declaration of Conflicting Interests
Jennifer N. Clements reports serving as a speaker for Eli Lilly and Novo Nordisk. Joshua J. Neumiller reports serving as an advisor for Bayer, Boehringer Ingelheim, Eli Lilly, and Proteomics International. Curtis Triplitt reports serving as a speaker for Novo Nordisk.
Funding
The authors declare having received no specific grant from a funding agency in the public, commercial, or not-for-profit sectors related to the content or development of this article.
Jennifer N. Clements, PharmD, FCCP, FADCES, BCPS, CDCES, BCACP, BC-ADM, is with University of South Carolina College of Pharmacy in Greenville, SC. Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP, is with Washington State University in Spokane, WA. Curtis Triplitt, PharmD, CDCES, FADCES, is with University of Texas Health at San Antonio and Texas Diabetes Institute, University Health System in San Antonio, TX.