Abstract
Objectives:
To describe daytime non-severe hypoglycemic events (NSHEs), assess their impact on patient functioning and diabetes self-management, and examine if these impacts differ by diabetes type or country.
Methods:
Internet survey to adults with diabetes in the US, UK, Germany, and France.
Results:
Of 6756 screened respondents, 2439 reported a daytime NSHE in the past month. NSHEs occurred while active (e.g., running errands) (45.1%), 29.6% while not active (e.g., watching TV), and 23.8% at work. On average, it took half a day to respond and recover from NSHE. Respondents monitored their glucose 5.7 extra times on average over the following week. On the day of event, type 1 respondents tested significantly more often than type 2 (p < 0.05). Type 2 were less likely to confirm NSHE with glucose test (p < 0.001). Following NSHE, 12.6% of respondents reduced total insulin by an average of 7.6 units (SD = 8.3). Total units and days with reduced dosing was significantly less, whilst number of additional glucose tests and time to recover was significantly longer if NSHE occurred at work (p < 0.001). Type 1 decreased insulin doses more often (p < 0.001); however, type 2 decreased a greater number of units (p < 0.01). Compared with other countries, US respondents were more likely to eat a light or full meal and respondents in France took significantly longer than all other countries to recognize (p < 0.05), respond to (p < 0.001), and recover from (p < 0.001) NSHE, used significantly more monitoring tests the day of (p < 0.05) and over the subsequent week (p < 0.001), and decreased their normal insulin dose more (p < 0.001). Limitations of the study include potential recall bias and selection bias.
Conclusions:
NSHEs are associated with a significant impact on patient functioning and diabetes management.
Introduction
Hypoglycemia, a common complication of insulin therapy for diabetes, is a significant burden to patients, and the critical limiting factor to achieving optimal glycemic control in diabetesCitation1–3. The impact of hypoglycemia can range from troubling symptoms, such as shakiness and sweating, to cognitive impairment or, in extreme cases, death. According to the American Diabetes AssociationCitation2, hypoglycemic events are categorized as either severe (requiring the assistance of another person to administer remedy) or non-severe (not requiring assistance from another person). To date, the majority of hypoglycemia research has focused on severe events, yet non-severe hypoglycemic events (NSHEs) are actually much more commonCitation4; they contribute to the cycle of recurrent hypoglycemia, and frequently precede episodes of severe hypoglycemiaCitation2. It has been estimated that patients with insulin-treated type 1 and type 2 diabetes experience an average of 43 and 16 non-severe symptomatic hypoglycemic episodes per year, respectivelyCitation4. For severe hypoglycemia, up to two episodes are experienced annually by patients with type 1 diabetes and approximately one episode in 5 years by patients with type 2 diabetesCitation4. Thus, for many insulin-treated patients, NSHEs are experienced frequentlyCitation3–6 and time spent on corrective actions and return to a normal level of functioning may be more extensive than previously believedCitation6.
NSHEs can occur at any time of the day and in a variety of settings (work vs at home) and during different degrees of physical activity (active vs sedentary). It has been found that ∼75% of patients with diabetes experienced an NSHE during the day while not at workCitation6 and that patients are at a higher risk of events when participating in physically demanding activities vs sedentary onesCitation7. These events have a negative effect on health-related quality-of-life (HRQoL)Citation8–11, work productivityCitation6, daily functionCitation5,Citation8, and costs of illnessCitation12. NSHEs are also associated with patient-initiated changes to diabetes self-management, including the frequency of self-monitoring of blood glucose testing, and greater use of blood glucose stripsCitation6.
Fear of repeat NSHEs may also have a significant impact on the kinds of activities patients participate in and on self-management of glucose levels. Patients may prioritize the immediate risk of hypoglycemia over considerations for long-term healthCitation3,Citation10 in that they may intentionally maintain blood glucose levels above target in order to minimize the frequency of the eventsCitation13. Evidence also indicates that type 1 and type 2 diabetic patients may differ in self-management strategies usedCitation5.
Little is known about the economic burden specific to non-severe hypoglycemia that does not require assistance from another person or immediate medical attention. Research associated with the economic burden of hypoglycemia emphasizes the medical costs associated with severe hypoglycemic events or focuses on the differences between therapies and the associated side-effects of hypoglycemia. A recent review of the literature on the burden of hypoglycemia in type 2 diabetes located only 11 studies, with eight emphasizing the medical costs and resource use associated primarily with severe hypoglycemiaCitation14. However, costs associated with mild or non-severe hypoglycemia can be indirect, such as work productivity problems, absenteeism from work or school, and out-of-pocket costs that include glucose monitoring test strips and food or drink for corrective actions taken. Research conducted in Sweden concluded that the indirect cost of a mild hypoglycemic event was €37.0 per event, to include lost wages and other indirect costsCitation12. Also in Sweden, direct and indirect costs of hypoglycemia were estimated to be US $12.9 and $14.1, respectively, per monthCitation15. In Canada, the mean out-of-pocket costs for patients in managing hypoglycemia was estimated to be $807 annually for type 1 diabetics and $679 for type 2 diabetics, with glucose monitoring test strips accounting for 39.2% of these costsCitation16. Researchers in the US have demonstrated that patients with hypoglycemia sustain greater activity impairment and reduced life productivity; among the employed, hypoglycemia is linked to 12.9% greater work impairment and 11.4% less work productivityCitation17. Similarly, data associated with the survey described in this paper have resulted in estimates of 8.3–15.9 hours of lost work time per month, with estimates of costs ranging from US $15.26–$93.57 per NSHECitation6.
Despite the frequency of these events, and indications that they may impact self-management behavior, the characteristics of NSHEs, how they differ depending upon the situation in which they occur, diabetes type, and the impacts these events have on diabetes self-management behavior is poorly understood.
The objective of the study is to describe daytime NSHEs, the situations in which they occur (what the person was doing when NSHE occurred), the characteristics of the event (how long they last, time for corrective actions, and time taken to recover from the event), and the impact these events have on diabetes self-management. Additionally the differences between type 1 and type 2 diabetes and country effects will be examined.
Patients and methods
Data were collected by a 20-minute survey designed to assess the impact of NSHEs on diabetes self-management and daily functioningCitation6. This survey was administered securely via the Internet to a panel of individuals aged ≥18 years with self–reported diabetes and residing in the US, UK, Germany, or France. The survey questions were designed based on a literature review, clinical expert input, and the qualitative analysis of interviews and focus groups conducted with adults with type 1 or type 2 diabetes who reported experiencing ≥1 NSHE in the preceding month. A total of eight focus groups were conducted in the US, UK, and France. To ensure content validity (relevant questions) and face-validity (no unfamiliar words or concepts for respondents), the survey was cognitive-debriefed and pilot-tested with six individuals. The final survey was translated into all relevant languages using a linguistic validation method outlined by an International Society for Pharmacoeconomics and Outcomes Research (ISPOR) task forceCitation18.
To avoid sourcing bias, individual survey respondents were recruited from a variety of online venues, including website advertising, affiliate networks, and email recruitment; respondents were also recruited via face-to-face or telephone interviews (this approach was used to identify individuals who were not frequently on-line). All respondents were screened initially to ensure that they self-reported that their diabetes was physician-diagnosed and that they were currently receiving diabetes treatment. In order to maintain proportionate response between categories, a stratified sampling procedure was applied. The stratification variables applied in the study were age (approximately equal distribution of 18–29, 30–49, 50–64, and ≥65 years) and diabetes type (∼50% each type 1 and type 2)Citation6. Eligible respondents were required to be able to read in the primary language of their country of residence. Respondents were remunerated the equivalent of $10.00 (USD) for completing the survey. The survey study was reviewed and approved by an Institutional Review Board.
The analysis sample for the current study comprises respondents who reported that they had experienced at least one daytime NSHE in the past month. Daytime events were further classified as either occurring (1) during the day while active (e.g., running errands) but not at work [Daytime–Active], (2) during the day but when not active (e.g., watching TV) [Daytime–Not Active], (3) during the day while at work, and (4) during the day while at school. Diabetes self-management variables included: length of time required to recognize and respond to the NSHE; time required to recover from the event; and subsequent adjustments to diabetes self-management (e.g., insulin dose adjustments, glucose monitoring frequency, healthcare provider follow-up, and/or intake of food or other supplements to stabilize blood glucose).
Results by country and by diabetes type are presented via frequencies or descriptive statistics (means and standard deviations), with differences explored using analysis of variance (ANOVA) for continuous variables and chi-square for proportions. Additionally, post-hoc tests (Scheffe’s procedure) were applied to evaluate differences between countries, independent of diabetes type. Observed significant country differences are reported for the countries that exhibited the greatest amount of difference (i.e., the spread between the highest and lowest values). In addition, certain responses for total units of insulin decreased due to an NSHE (>46 units) and number of extra blood glucose tests after an NSHE (>28 tests) contained outliers, or observations that appeared to be inconsistent with other observations in the data set. To account for these departures from normality, a 5% trim was employedCitation19.
Results
Analytic sample
A total of 6756 individuals with diabetes were screened. Of these, 2439 had experienced ≥1 daytime NSHE at any time in the past month, had complete, analyzable data, and were the analysis sample for this paper (see ).
Figure 1. Sample composition.
Sample description
The mean age of the sample was 45.7 years (SD = 14.7), predominately female (56.3%), and Caucasian (76.3%), with a mean duration of diabetes of 12.7 (SD = 12.7) years. Type 1 respondents were significantly younger (p < 0.001), more often female (p < 0.01), had diabetes for a longer duration (p < 0.001), and more often confirmed their NSHE with a blood glucose test than type 2 respondents. Further, the US had significantly older respondents who had diabetes for a longer duration than the other countries (p < 0.001).
and present the full sample description.
Table 1. Demographic and daytime NSHE characteristics.
Table 2. Demographic and daytime NSHE characteristics.
Description of event
Four hundred and twenty-two respondents (38.9%) reported experiencing their most recent NSHE in the past week (≤7 days), 30.5% in the last 2 weeks (>7 days and <14 days), and 30.7% reported experiencing their NSHE in the last month, but more than 2 weeks prior.
When examining all NSHEs in the past month, the majority of events occurred while respondents were active, for example running errands or during sports (45.1% of total events), while 29.6% occurred when not active, 23.8% occurred while at work, and 1.5% occurred while at school. One hundred and eighty-eight (7.7%) of the total sample reported being a student and, of these, 104 (55.3%) were also currently working for pay. Due to the low report of events occurring during school, this group has been removed from subsequent analyses.
The majority of hypoglycemic events were confirmed by blood glucose monitoring (58.8%). On average it took respondents almost half a day to recognize, respond to, and recover from their event. The majority of this time (on average close to 11 h) was spent recovering from the event rather than the period when experiencing or responding to their acute symptoms. Respondents having daytime NSHEs at work spent a longer time recovering from the event (p < 0.001) than they did for daytime active events.
Corrective actions and diabetes management (see Table 3)
For the most part, respondents used glucose tablets/gel or ate sweet candy, cake, or drinks to counteract their NSHE. However, almost a quarter of respondents (23.6%) ate a light meal as a corrective action.
On average, respondents monitored their glucose 5.7 extra times (SD = 7.4) over the subsequent 7 days after the NSHE than they would have if they had not had the NSHE. This number of additional tests was significantly greater for events when they occurred at work than for NSHEs which occurred either while not at work and active (p < 0.001) or while not active (p < 0.05).
Further, 12.6% of the sample reduced their total units of insulin taken, an average of 7.6 (SD 8.3) units. If the NSHE occurred while at work, the total amount of insulin reduced and the number of days they reduced their insulin dose was significantly less than if the event occurred while not at work (p < 0.001).
Differences by diabetes type
Description of event
Type 2 respondents were significantly older than type 1 respondents (p < 0.001), more often male (p < 0.01), and were less likely to confirm their NSHE symptoms with a glucose monitoring test (p < 0.001) (see and ). There were no significant differences between diabetes type in the amount of time recognizing, dealing with, or recovering from the NSHE.
Corrective actions and diabetes management (see )
Type 2 respondents were more likely to eat a light meal (p < 0.001), whereas type 1 respondents were more likely to eat (p < 0.001) or drink (p < 0.01) something sweet.
Table 3. Impact of daytime NSHEs on diabetes self-management by level of activity.
Table 4. Impact of daytime NSHEs on diabetes self-management by diabetes type.
Table 5. Impact of daytime NSHEs on diabetes self-management by country.
Over a 7-day period there were no differences in the number of extra glucose monitoring tests done; however, on the day of the event, type 1 respondents tested significantly more often than type 2 respondents (p < 0.05).
Type 1 respondents also decreased their normal insulin doses more often than type 2 respondents (p < 0.001); however, type 2 respondents decreased their insulin by a greater number of units (p < 0.01). There were no significant differences between diabetes types’ duration of insulin dose decrease.
Differences by country
Description of event
Differences between countries in terms of where their daytime NSHEs occurred were found for events which occurred while not active (p < 0.01) or at work (p < 0.001) (see Table 5). Respondents in France took significantly longer than respondents in all other countries to recognize (p < 0.05), respond to (p < 0.001), and recover from (p < 0.001) the NSHE. They also used significantly more glucose monitoring tests both the day of (p < 0.05) and over the subsequent week (p < 0.001) than respondents in any other country.
Corrective actions and diabetes management
Respondents in the US were more likely to eat either a light meal or full meal than respondents in other countries. Additionally, more respondents in France decreased their normal insulin dose (p < 0.001), although there were no differences between countries for the amount of insulin dose reduction.
Discussion
These findings strongly suggest that NSHEs are not without significant impact on patient functioning and diabetes management, regardless of where they occur or whether a person has type 1 or type 2 diabetes, and support previous findingsCitation3–11. For example, our data demonstrates that NSHEs are not infrequent. Over one-third of the survey sample (2439 or 36%) reported ≥1 daytime NSHE at anytime during the previous month. Additionally, a majority of respondents to the survey experienced hypoglycemic events while physically active and not at work, which is also supported by the literatureCitation6,Citation7. However, NSHEs which occur while a person is active will last a shorter period of time than those events which occur while not active or at work, suggesting that, when patients are active, they may be more vigilant and quicker to respond to an NSHE. Despite the fact that NSHEs which occurred while not active took the longest to recover from (although only slightly longer than work events), NSHEs at work resulted in significantly more glucose monitoring tests as well as fewer people adjusting their usual insulin dose, suggesting that more frequent monitoring after an NSHE may be helpful for patients to correctly adjust their insulin following an event.
Furthermore, the time spent on corrective action and recovery was substantial, with the potential to impact health-related quality-of-life (HRQoL), work productivity, and daily function. This compares similarly to previous studiesCitation5,Citation6,Citation8–11. Following the NSHE, respondents in this study reported that they reduce their insulin, which suggests that they may intentionally keep blood sugar high in order to avoid further NSHEs, a strategy also noted in previous studiesCitation3,Citation10,Citation13.
The comparison of NSHE between four countries is a novel contribution of this study. Respondents in France experienced longer response and recovery times, and used more glucose monitoring tests following an NSHE. More respondents in France decreased their insulin dose following an NSHE. What is unclear from these data is the extent to which these differences are due to differences in health system access, clinical practice, or diabetes education strategies and information provision to patients across countries. Additionally, socio-cultural sentiment about self-management of health concerns may play a role in these distinctions. There are many possibilities for explaining both similarities and differences across countries, and more research is needed in order to better understand cross-country differences in the management of NSHEs.
These findings may also offer some insight into why healthcare practitioners, in general, may tend to underplay the importance or incidence of these non-severe eventsCitation20. According to these respondents, far less time and effort is spent in the acute phase of an NSHE experiencing and reacting to symptoms: in line with the common wisdom that these events are over in a short time and that a glass of juice or a sweet is all that is needed. However, these findings suggest that one must also look beyond the acute phase and regard the recovery phase or the total time spent before one is functioning at a normal level, to accurately understand the importance of an NSHE for patients functioning and well-being. The total time spent on these events, including the recovery phase, last considerably longer—up to days for some patients, during which time functioning and diabetes management continues to be negatively impacted.
These data indicate that patients monitor their blood glucose more frequently after the NSHE, and this additional monitoring may translate into an economic burden for patients who often must pay for glucose monitoring strips out-of-pocket. Additionally, as monitoring rates vary by country, this may partially explain some country-specific differences in the economic burden of these events. Further research is needed to better understand the economic burden of NSHEs generally, including how economic burden might differ by country and by health system.
There are limitations to this study design that should be considered. As with any self-report method, recall bias influences the data and its findings. However, with regard to hypoglycemia, at least one study has demonstrated that hypoglycemic event recall of up to 1 week can be considered accurateCitation21. In the current study, a majority of respondents reported NSHEs that had occurred within the previous 2 weeks. Given this time frame, we consider the risks of recall bias to be relatively small. Additionally, findings from focus groups conducted prior to survey implementation suggest that recall was relatively accurate up to 1 month. Furthermore, selection bias is a possibility with any internet-based survey as only those with access to computers and the ability to use them are able to participate. Mitigating this potential bias is the fact that computer literacy is high in all of the countries included in this study. For example, the UK has a 99% literacy rate and 51.4 million internet users out of 63.5 million inhabitantsCitation22. Accuracy of participant response could also have been affected by the paid incentive for participating; however, the incentive was kept small in order to avoid this potential bias. Last, eligibility for the study only required a self-reported physician diagnosis of diabetes. However, it was not known to participants that only those with diabetes would be administered the survey, and we believe that this feature of the survey administration was an important safeguard to avoid misrepresentation of diagnosis.
Conclusions
In conclusion, NSHEs are not minor events in the day-to-day functioning and diabetes management of patients. A greater understanding of the impact of these events in terms of time spent both dealing with and recovering from an NSHE as well as the adjustments that patients make in their diabetes management as a result of the event, would better inform healthcare practitioners and facilitate improvements in patient expectations and education around managing these events.
Transparency
Declaration of funding
This study was funded by Novo Nordisk A/S. Mr Christensen contributed to the survey design and preparation of the manuscript.
Declaration of financial or other relationships
Dr Brod and Mr Bushnell are advisors/paid consultants to Novo Nordisk A/S. Mr Christensen is an employee of Novo Nordisk A/S.
Acknowledgments
No assistance in the preparation of this article is to be declared.
Related Research Data
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