Diabetes Care
1
Ulrik Pedersen-Bjergaard,1,2 Louise Færch,1 Marie-Louise Allingbjerg,1 Rikke Agesen,1,2 and Birger Thorsteinsson1,2
DOI: 10.2337/dc14-1417
OBJECTIVE
We test the hypotheses that the implementation in Denmark of new, stricter European Union (EU) legislation on driver’s licensing, with the purpose to improve traffic safety in January 2012, has reduced the self-reported rate of severe hypoglycemia in a routine clinical setting and that anonymous reporting results in higher event rates. RESEARCH DESIGN AND METHODS
A cohort of 309 patients with type 1 diabetes was recruited in the outpatient clinic at Nordsjællands University Hospital Hillerød, Denmark. Yearly numbers of severe hypoglycemic events defined by need for treatment assistance from another person were retrieved from medical records in the years 2010 to 2012 and retrospectively reported in an anonymous questionnaire. Data from medical records in 2012 were compared with those from 2010 and 2011 and with data from the questionnaire. RESULTS
Reported rates of severe hypoglycemia in the medical records were reduced by 55% in 2012 compared with the prior years (P = 0.034). The proportion of subjects reporting recurrent episodes was grossly reduced from 5.6 to 1.5% (P = 0.014). Compared with anonymous reporting in the questionnaire, the rate of severe hypoglycemia in 2012 was 70% lower (P < 0.001). CONCLUSIONS
1
Reporting of severe hypoglycemia by patients with type 1 diabetes is significantly reduced following implementation of EU driver’s licensing legislation that implies withdrawal of driver’s licensing in case of recurrent episodes within 1 year. The resulting burden of concealed severe hypoglycemia may impair the safety of affected patients and unintentionally paradoxically reduce the general traffic safety. Occurrence of severe hypoglycemia with cognitive disruption and impaired self-care is the main side effect of insulin therapy in type 1 diabetes, representing a threat toward safety and well-being of the patients (1). Knowledge about occurrence of hypoglycemia in the individual patient is a prerequisite to reduce the risk of future
Department of Cardiology, Nephrology, and Endocrinology, Nordsjællands Hospital Hillerød, Hillerød, Denmark 2 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Corresponding author: Ulrik Pedersen-Bjergaard, [email protected]. Received 6 June 2014 and accepted 2 September 2014. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Diabetes Care Publish Ahead of Print, published online October 6, 2014
CLIN CARE/EDUCATION/NUTRITION/PSYCHOSOCIAL
The Influence of New European Union Driver’s License Legislation on Reporting of Severe Hypoglycemia by Patients With Type 1 Diabetes
2
Driver’s License and Reporting of Hypoglycemia
episodes. Assessment of hypoglycemia is therefore mandatory and should be made at every outpatient visit. Even mild hypoglycemia reduces driving performance and decision making, and severe hypoglycemia may lead to motor vehicle accidents when occurring during driving (2–7). Consequently, driver’s licensing for patients with type 1 diabetes requires an assessment of the future risk of severe hypoglycemia to be low (2,8,9). The legislation on driver’s licensing, however, varies considerably between countries. In Europe, this has led to the elaboration of the European Union Third Directive on Driving in 2006 (10,11), implemented in Denmark 1 January 2012. The novel key point representing a major tightening compared with previous Danish legislation is that occurrence of two or more yearly episodes of severe hypoglycemia disqualifies the patient from obtaining and maintaining a driver’s license. Prior to implementation, these new rules were widely debated in the diabetic community and the public media, as they were claimed to represent a threat toward driver’s licensing for many type 1 diabetic patients. Thus Danish surveys have consistently reported a proportion of type 1 diabetic patients reporting at least two episodes per year of 20% (12,13). This corresponds to ;6,000 Danish patients with endangered driver’s licensing. Such patients facing the risk of losing their driver’s license may be discouraged to inform their health care providers about severe hypoglycemia. The aim of this study was to test the hypothesis that implementation of the novel European Union (EU) legislation on driver’s licensing is followed by reduced reporting of severe hypoglycemia in a routine clinical care setting. A further purpose was to compare clinic reporting to that in a study setting in which patients are aware of data anonymization. RESEARCH DESIGN AND METHODS
The study was a retrospective cohort study and was approved by the Committee on Biomedical Ethics of the Copenhagen Capital Region (H-4–2011–043). A total of 416 consecutive adult patients with type 1 diabetes for more than 1 year attending the outpatient clinic at Nordsjællands University Hospital Hillerød were invited to participate in the
Diabetes Care
study. Following written informed consent, 309 patients (74.3%) were willing to participate. Type 1 diabetes was defined by insulin treatment from the time of diagnosis and unstimulated C-peptide less than 300 pmol/L or stimulated (venous blood glucose concentration .12 mmol/L) C-peptide less than 600 pmol/L. Pregnant women and subjects suffering from severe concomitant disease were excluded from participation. Baseline clinical data were extracted from the medical records, and random C-peptide concentration was measured as previously reported (14). Hypoglycemia awareness was self-estimated by a validated method (14) that is recommended in the Danish guidelines for treatment of type 1 diabetes issued by the National Board of Health (15). Patients were recruited for participation in a cross-sectional survey from November 2011 to May 2013 and completed a questionnaire composed of validated questions on hypoglycemia after ensuring a common understanding of the questions and definitions used (12). The patients were informed that the data remain confidential and anonymized following incorporation into a database according to Danish data legislation. The core question was “How many episodes of severe hypoglycemia needing treatment assistance from another person have you had during the last year?” This definition of severe hypoglycemia is in accordance with the recommendations by the American Diabetes Association Workgroup on Hypoglycemia (16) and the recall within 1 year is well preserved and proven valid (14). Subsequently, medical records were scrutinized for occurrence of severe hypoglycemia in the 2 years before (2010 and 2011) and the year following (2012) implementation of EU regulations on driver’s licensing. Outpatient clinic data on severe hypoglycemia has been systematically collected (consistently using the same definition as above) at each 3- to 4-monthly visit during the last decade. The question posed to the patient as an integrated part of the consultation is “How many episodes of severe hypoglycemia needing treatment assistance from another person have you had since your last visit?” The number is documented on the diabetes summary chart. This practice has not been subject to changes during the study period. Mean
HbA1c level and insulin regimen and dose were also extracted for each of the calendar years: 2010, 2011, and 2012. Statistics
The sample size was aimed to be in the range of that of previous studies of severe hypoglycemia in cohorts of type 1 diabetic patients yielding robust results (14,17–20). Rates of severe hypoglycemia are given as mean (range). Other values shown in the text and tables are mean (SD) or n (%). Data coverage for each year is calculated as percentage of the year covered by valid data. Yearly rates of severe hypoglycemia are corrected for data completeness. Standard descriptive and comparative statistics are used as appropriate. Rates of severe hypoglycemia are compared by Wilcoxon signed ranks test. RESULTS
The baseline clinical characteristics of the participants are shown in Table 1. The proportion of subjects with risk factors for severe hypoglycemia such as hypoglycemia unawareness (13.9%) and undetectable C-peptide concentration (75.1%) are as expected in a representative random sample of patients with type 1 diabetes (12,13). From a mean yearly rate of severe hypoglycemic events in the medical records of 0.42 (0–6.5) events per patientyear in 2010 to 2011, the rate in 2012 was reduced by 55% to 0.19 (0–5) events per patient-year (P = 0.034) (Table 2 and Fig. 1). This was predominantly due to a 73% relative reduction in the proportion of subjects reporting recurrent (two or more) episodes (absolute reduction from 5.6 to 1.5% [P = 0.014]), whereas the number of subjects reporting solitary episodes within each calendar year was not significantly reduced (P = 0.88) (Fig. 2). There was no difference in reporting patterns between the sexes, and the decline in reporting was not associated with age or with hypoglycemia awareness class (not shown). The mean HbA 1 c level of 8.0% (1.1%) (64 [12] mmol/mol) in 2010 was reduced to 7.7% (1.0) (61 [11] mmol/mol) in 2012 (P = 0.035) (Table 2). There was a significant reduction of data coverage from 2010 to 2011 (P , 0.001), but no difference between 2011 and 2012 (Table 2). A number of patients were transferred to insulin analogs,
care.diabetesjournals.org
Pedersen-Bjergaard and Associates
Table 1—Baseline characteristics Demographics and clinical characteristics
n = 309
Women
118 (38.2)
Age (years)
52.4 (13.9)
Duration of diabetes (years)
23 (14)
Retinopathy
169 (54.7)
Nephropathy
41 (13.3)
BMI (kg/m2)
25.5 (4.0)
Hypertension
76 (24.6)
C-peptide negative Hypoglycemia awareness Normal Impaired Unaware Missing
232 (75.1) 133 (43.0) 130 (42.1) 43 (13.9) 3 (1.0)
Severe hypoglycemia (events per patient-year) Mean rate Range
0.63 0–15
Data are presented as mean (SD) or n (%) unless otherwise indicated.
and the number of patients on continuous subcutaneous insulin infusion (CSII) increased from 28 to 49 (P = 0.014) (Table 2). Exclusion of subjects commencing CSII therapy did not affect the annually reported rates of severe hypoglycemia significantly. The rate of 0.19 (0–5) episodes per patient-year reported in the medical records in 2012 was 70% lower than the annual rate of severe hypoglycemia of 0.63 (0–15) episodes per patient-year obtained in the questionnaire survey (P , 0.001) (Fig. 1). The main reason for this difference is a more than sevenfold higher proportion of subjects reporting recurrent episodes in the questionnaire (11.4 vs. 1.5%; P =
0.0046) (Fig. 2). There was no difference between the proportions reporting solitary events (P = 0.48). The difference between study reporting and clinic reporting was not associated with sex, age, or awareness class (not shown). CONCLUSIONS
This study demonstrates an immediate halving in reporting of severe hypoglycemia in a routine clinical setting following implementation of new EU regulations on driver’s licensing. The reduction was not explained by relaxation of metabolic control or by any specific intervention in the cohort, and therefore, it is probably not a true rate reduction. This is further supported by the
Table 2—Temporal development in rates of severe hypoglycemia as indicated in medical records, HbA1c levels, and insulin treatment regimens Year 2010
2011
2012
Data coverage (%)
81.7
65.4
66.1
Severe hypoglycemia Mean rate per patient-year Range
0.36 0–7
0.47 0–11
0.19 0–5
Insulin doses (IU/day)
51.2 (22.0)
49.8 (21.9)
49.5 (22.1)
Insulin regimen Analog basal-bolus Human basal-bolus Mixed basal-bolus CSII Other
113 (36.6) 48 (15,5) 55 (17.8) 28 (9.1) 65 (21.0)
125 (40.5) 46 (14.9) 48 (15.5) 38 (12.3) 52 (16.8)
128 (41.4) 41 (13.3) 55 (17.8) 49 (15.9) 36 (11.6)
HbA1c (%)
8.0 (1.1)
7.8 (1.1)
7.7 (1.0)
HbA1c (mmol/mol)
64 (12)
62 (12)
61 (11)
Data are presented as mean (SD) or n (%) unless otherwise indicated.
fact that the rate of severe hypoglycemia in the general type 1 diabetic population has only declined marginally during the past decades despite the introduction of a range of new therapeutic measures (12–14,17–20). The reduction was primarily due to a pronounced decline in the proportion of patients reporting recurrent events. This is noteworthy because a key operational point in the new EU regulations is that occurrence of two or more episodes of severe hypoglycemia within 12 months imposes withdrawal of driver’s licensing (10,11). This particular issue has been heavily debated in the mass media, with major contributions from the Danish Diabetes Association, and is presumably common knowledge to all patients with diabetes. In accordance, a recent Danish survey exploring the reluctance to report severe hypoglycemia by patients with type 1 diabetes reported that more than one-third of patients holding a driver’s licensedin particular, those prone to severe hypoglycemiad would consider keeping the episodes for themselves if their license would be endangered by reporting (21). Anonymous reporting may encourage some patients to report more accurate numbers of events. This was apparent by a threefold higher rate of severe hypoglycemia in the questionnaire survey when compared with that retrieved from the medical records. Again, the difference was almost exclusively due to different reporting of recurrent episodes. A previous large Danish anonymous survey in 2006 (13) included 500 consecutive patients from our clinic with clinical characteristics comparable to those of the actual cohort and yielded a rate of severe hypoglycemia of 0.86 episodes per patient-year (unpublished data from Kristensen et al. [13]), thus somewhat higher compared with the 0.63 episodes per patient-year in this study. The difference may be accounted for by systematic efforts in the clinic to reduce the rate, but a bias introduced by the driver’s licensing legislation on willingness to participate in a survey on hypoglycemia or on reportingd although anonymousdcannot be excluded. Finally, even patients’ own anonymous estimates in studies may be subject to underreporting, as rates of severe hypoglycemia obtained from spouses are often significantly higher
3
4
Driver’s License and Reporting of Hypoglycemia
Diabetes Care
Figure 1—Mean annual rates of severe hypoglycemia obtained in an anonymous questionnaire survey and from medical records before and after the 1 January 2012 implementation of new EU legislation on driver’s licensing in Denmark.
than those reported by the patients (22,23). The study is strengthened by the thorough routine collection of hypoglycemic data in this clinic but, on the other hand, limited by not having a true prospective design. A reluctance to ask about and document severe hypoglycemia may include some health care professionals due to a misunderstood empathy for the patients. The potential impact of the latter cannot be estimated from the study, but the fact that data completeness was similar in 2011 and 2012 is argument against a major contribution. The clinical characteristics of the
participants and the rate of severe hypoglycemia in our clinic obtained under similar study conditions are comparable to those of other clinics (12,13), and consequently, the results are likely to be generalizable. The study shows that the estimated proportion of concealed severe hypoglycemia has now grown to approximately two-thirds of all episodes. There are several potential risks of such a burden of hidden severe hypoglycemia. At the individual patient level, this precludes from rational intervention against recurrent severe hypoglycemia. Facing a patient with recurrent
Figure 2—Proportion of patients with solitary and recurrent (two or more) episodes of severe hypoglycemia in an anonymous questionnaire (left columns) and as documented in the medical records in 2010, 2011, and 2012. SH, severe hypoglycemia.
severe hypoglycemia, a number of specific interventions may be considered: lifestyle intervention, including snacking and intensified self-monitoring; relaxation of glycemic target; changing insulin regimen; optimizing the use of bolus insulin, including carbohydrate counting; specific interventions for improvement of hypoglycemia awareness; and use of technology in terms of CSII and/or continuous glucose monitoring (24–27). By not being offered these opportunities, the patient may remain at continued risk of recurrent severe hypoglycemia and its consequences in terms of risk of accidents and reduced quality of life (1). As for the society, incremental concealed severe hypoglycemia may increase the risk of hypoglycemia-related traffic accidents. This may in fact be an unintended paradoxical result of the EU legislation as it stands. According to several surveys, ;20% of all type 1 diabetic patients will at a given time be at danger of revoked driver’s license (12,13). A reanalysis of data from the Diabetes Control and Complications Trial (DCCT)d which specifically excluded subjects with recurrent severe hypoglycemiad estimated that up to 30% of the participants would have had their license revoked at some time during the trial (28). Thus a very large proportion of patients with type 1 diabetes faces the risk of further stigmatization and may be tempted not to report recurrent severe hypoglycemia to their health care providers. For the benefit of the treatment of type 1 diabetes as well as traffic safety, it can be argued that granting of driver’s licensing should rely more on an individual risk assessment, as also recommended by the American Diabetes Association (2), including a documentation of proper self-care (self-monitoring and snacking) when driving, rather than operate on reported occurrence of severe hypoglycemia that is not a valid measure when the driver’s license is endangered. In conclusion, rates of severe hypoglycemia reported by patients with type 1 diabetes in routine clinical practice are immediately halved following implementation of the new EU directive on driver’s licensing. We acknowledge the importance of legislation on driver’s licensing because hypoglycemia impairs driving capacity (4–7). However, the recently altered Danish legislation seems to impose a threat against maintenance
care.diabetesjournals.org
of the physician-patient relationship necessary to improve long-term outcomes. Information about severe hypoglycemia in medical records only represent the tip of the iceberg, and it is therefore of utmost importance to improve the dialogue with the patients about this major clinical problem and its prevention.
Acknowledgments. The authors thank re-
search nurses Tove Larsen, Pernille Banck, and Charlotte Hansen, Department of Cardiology, Nephrology, and Endocrinology, Nordsjællands University Hospital Hillerød, for data collection and management. Funding. The study was funded by a grant from the Research Foundation of Nordsjællands University Hospital Hillerød, the Beckett Foundation, and the Foundation of Captain Lieutenant Harald Jensen and Wife. B.T. received core funding from Nordsjællands University Hospital Hillerød. Duality of Interest. U.P.-B. served on advisory boards for AstraZeneca/Bristol Myers Squibb and Novo Nordisk and received lecture fees from AstraZeneca/Bristol Myers Squibb, Sanofi Aventis, and Novo Nordisk. L.F. is now employed by Novo Nordisk. B.T. served on advisory boards for Eli Lilly. No other potential conflicts of interest relevant to this article were reported. Author Contributions. U.P.-B. initiated and designed the study, performed the data analysis, and drafted the first version of the manuscript. L.F. initiated and designed the study and participated in the collection of data. M.-L.A. and R.A. participated in the collection of data. B.T. initiated and designed the study. All authors have contributed to, read, and approved the final manuscript. U.P.-B. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented at the 74th Scientific Sessions of the American Diabetes Association, San Francisco, 13–17 June 2014.
References 1. Frier BM. How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev 2008;24:87–92 2. Lorber D, Anderson J, Arent S, et al.; American Diabetes Association. Diabetes and driving. Diabetes Care 2014;37(Suppl. 1):S97–S103 3. Frier BM. Driving and diabetes. BMJ 1992; 305:1238–1239 4. Cox DJ, Penberthy JK, Zrebiec J, et al. Diabetes and driving mishaps: frequency and
Pedersen-Bjergaard and Associates
correlations from a multinational survey. Diabetes Care 2003;26:2329–2334 5. Cox DJ, Gonder-Frederick LA, Kovatchev BP, Julian DM, Clarke WL. Progressive hypoglycemia’s impact on driving simulation performance. Occurrence, awareness and correction. Diabetes Care 2000;23:163–170 6. Cox DJ, Kovatchev BP, Anderson SM, Clarke WL, Gonder-Frederick LA. Type 1 diabetic drivers with and without a history of recurrent hypoglycemia-related driving mishaps: physiological and performance differences during euglycemia and the induction of hypoglycemia. Diabetes Care 2010;33:2430–2435 7. Stork ADM, van Haeften TW, Veneman TF. The decision not to drive during hypoglycemia in patients with type 1 and type 2 diabetes according to hypoglycemia awareness. Diabetes Care 2007;30:2822–2826 8. Diabetes and Driving in Europe. A report of the Second European Working Group on Diabetes and Driving, an advisory board to the Driving Licence Committee of The European Union [Internet], 2006. Available from http://ec.europa.eu/ transport/road_safety/pdf/behavior/diabetes_ and_driving_in_europe_final_1_en.pdf. Accessed 3 January 2014 9. Inkster B, Frier BM. Diabetes and driving. Diabetes Obes Metab 2013;15:775–783 10. European Parliament; Council of the European Union. Directive 2006/126/EC of the European parliament and of the council of 20 December 2006 on driving licences (Recast). Off J Eur Union 2006;L403:18–60 11. European Parliament; Council of the European Union. Commission directive 2009/113/EC of 25 August 2009 amending directive 2006/ 126/EC of the European Parliament and of the Council on driving licences. Off J Eur Union 2009;L223:31–35 12. Pedersen-Bjergaard U, Pramming S, Heller SR, et al. Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection. Diabetes Metab Res Rev 2004;20:479–486 13. Kristensen PL, Hansen LS, Jespersen MJ, et al. Insulin analogues and severe hypoglycaemia in type 1 diabetes. Diabetes Res Clin Pract 2012;96:17–23 14. Pedersen-Bjergaard U, Pramming S, Thorsteinsson B. Recall of severe hypoglycaemia and self-estimated state of awareness in type 1 diabetes. Diabetes Metab Res Rev 2003;19:232–240 15. Kliniske retningslinier for behandling af voksne med type 1 diabetes [Internet]. Available from http://www.endocrinology.dk/index.php/ nbvhovedmenu/nationale-rapporter-omendokrinologiske-emner/1-diabetes-mellitus-2 16. Seaquist ER, Anderson J, Childs B, et al.; American Diabetes Association; Endocrine Society. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association
and the Endocrine Society. J Clin Endocrinol Metab 2013;98:1845–1859 17. Pramming S, Thorsteinsson B, Bendtson I, Binder C. Symptomatic hypoglycaemia in 411 type 1 diabetic patients. Diabet Med 1991;8: 217–222 18. MacLeod KM, Hepburn DA, Frier BM. Frequency and morbidity of severe hypoglycaemia in insulin-treated diabetic patients. Diabet Med 1993;10:238–245 19. ter Braak EW, Appelman AM, van de Laak M, Stolk RP, van Haeften TW, Erkelens DW. Clinical characteristics of type 1 diabetic patients with and without severe hypoglycemia. Diabetes Care 2000;23:1467–1471 20. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50:1140–1147 21. Bagger M, Dømgaard M, Rhee NA, Burton CM, Thorsteinsson B. What drives patients? A cross-sectional survey of the effects and fear of hypoglycaemia on individuals, workplace and patients’ continued eligibility to drive. Diabetologia 2014;57(Suppl. 1):S428 22. Jørgensen HV, Pedersen-Bjergaard U, Rasmussen AK, Borch-Johnsen K. The impact of severe hypoglycemia and impaired awareness of hypoglycemia on relatives of patients with type 1 diabetes. Diabetes Care 2003;26: 1106–1109 23. Heller S, Chapman J, McCloud J, Ward J. Unreliability of reports of hypoglycaemia by diabetic patients. BMJ 1995;310:440 24. Cox DJ, Gonder-Frederick L, Polonsky W, Schlundt D, Kovatchev B, Clarke W. Blood glucose awareness training (BGAT-2): long-term benefits. Diabetes Care 2001;24:637–642 25. Leelarathna L, Little SA, Walkinshaw E, et al. Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial. Diabetes Care 2013;36:4063–4070 26. Choudhary P, Ramasamy S, Green L, et al. Real-time continuous glucose monitoring significantly reduces severe hypoglycemia in hypoglycemia-unaware patients with type 1 diabetes. Diabetes Care 2013;36:4160–4162 27. Pedersen-Bjergaard U, Kristensen PL, BeckNielsen H, et al. Effect of insulin analogues on risk of severe hypoglycaemia in patients with type 1 diabetes prone to recurrent severe hypoglycaemia (HypoAna trial): a prospective, randomised, open-label, blinded-endpoint crossover trial. Lancet Diabetes Endocrinol 2014;2:553– 561 28. Kilpatrick ES, Rigby AS, Warren RE, Atkin SL. Implications of new European Union driving regulations on patients with Type 1 diabetes who participated in the Diabetes Control and Complications Trial. Diabet Med 2013;30:616– 619
5
1
Ulrik Pedersen-Bjergaard,1,2 Louise Færch,1 Marie-Louise Allingbjerg,1 Rikke Agesen,1,2 and Birger Thorsteinsson1,2
DOI: 10.2337/dc14-1417
OBJECTIVE
We test the hypotheses that the implementation in Denmark of new, stricter European Union (EU) legislation on driver’s licensing, with the purpose to improve traffic safety in January 2012, has reduced the self-reported rate of severe hypoglycemia in a routine clinical setting and that anonymous reporting results in higher event rates. RESEARCH DESIGN AND METHODS
A cohort of 309 patients with type 1 diabetes was recruited in the outpatient clinic at Nordsjællands University Hospital Hillerød, Denmark. Yearly numbers of severe hypoglycemic events defined by need for treatment assistance from another person were retrieved from medical records in the years 2010 to 2012 and retrospectively reported in an anonymous questionnaire. Data from medical records in 2012 were compared with those from 2010 and 2011 and with data from the questionnaire. RESULTS
Reported rates of severe hypoglycemia in the medical records were reduced by 55% in 2012 compared with the prior years (P = 0.034). The proportion of subjects reporting recurrent episodes was grossly reduced from 5.6 to 1.5% (P = 0.014). Compared with anonymous reporting in the questionnaire, the rate of severe hypoglycemia in 2012 was 70% lower (P < 0.001). CONCLUSIONS
1
Reporting of severe hypoglycemia by patients with type 1 diabetes is significantly reduced following implementation of EU driver’s licensing legislation that implies withdrawal of driver’s licensing in case of recurrent episodes within 1 year. The resulting burden of concealed severe hypoglycemia may impair the safety of affected patients and unintentionally paradoxically reduce the general traffic safety. Occurrence of severe hypoglycemia with cognitive disruption and impaired self-care is the main side effect of insulin therapy in type 1 diabetes, representing a threat toward safety and well-being of the patients (1). Knowledge about occurrence of hypoglycemia in the individual patient is a prerequisite to reduce the risk of future
Department of Cardiology, Nephrology, and Endocrinology, Nordsjællands Hospital Hillerød, Hillerød, Denmark 2 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Corresponding author: Ulrik Pedersen-Bjergaard, [email protected]. Received 6 June 2014 and accepted 2 September 2014. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Diabetes Care Publish Ahead of Print, published online October 6, 2014
CLIN CARE/EDUCATION/NUTRITION/PSYCHOSOCIAL
The Influence of New European Union Driver’s License Legislation on Reporting of Severe Hypoglycemia by Patients With Type 1 Diabetes
2
Driver’s License and Reporting of Hypoglycemia
episodes. Assessment of hypoglycemia is therefore mandatory and should be made at every outpatient visit. Even mild hypoglycemia reduces driving performance and decision making, and severe hypoglycemia may lead to motor vehicle accidents when occurring during driving (2–7). Consequently, driver’s licensing for patients with type 1 diabetes requires an assessment of the future risk of severe hypoglycemia to be low (2,8,9). The legislation on driver’s licensing, however, varies considerably between countries. In Europe, this has led to the elaboration of the European Union Third Directive on Driving in 2006 (10,11), implemented in Denmark 1 January 2012. The novel key point representing a major tightening compared with previous Danish legislation is that occurrence of two or more yearly episodes of severe hypoglycemia disqualifies the patient from obtaining and maintaining a driver’s license. Prior to implementation, these new rules were widely debated in the diabetic community and the public media, as they were claimed to represent a threat toward driver’s licensing for many type 1 diabetic patients. Thus Danish surveys have consistently reported a proportion of type 1 diabetic patients reporting at least two episodes per year of 20% (12,13). This corresponds to ;6,000 Danish patients with endangered driver’s licensing. Such patients facing the risk of losing their driver’s license may be discouraged to inform their health care providers about severe hypoglycemia. The aim of this study was to test the hypothesis that implementation of the novel European Union (EU) legislation on driver’s licensing is followed by reduced reporting of severe hypoglycemia in a routine clinical care setting. A further purpose was to compare clinic reporting to that in a study setting in which patients are aware of data anonymization. RESEARCH DESIGN AND METHODS
The study was a retrospective cohort study and was approved by the Committee on Biomedical Ethics of the Copenhagen Capital Region (H-4–2011–043). A total of 416 consecutive adult patients with type 1 diabetes for more than 1 year attending the outpatient clinic at Nordsjællands University Hospital Hillerød were invited to participate in the
Diabetes Care
study. Following written informed consent, 309 patients (74.3%) were willing to participate. Type 1 diabetes was defined by insulin treatment from the time of diagnosis and unstimulated C-peptide less than 300 pmol/L or stimulated (venous blood glucose concentration .12 mmol/L) C-peptide less than 600 pmol/L. Pregnant women and subjects suffering from severe concomitant disease were excluded from participation. Baseline clinical data were extracted from the medical records, and random C-peptide concentration was measured as previously reported (14). Hypoglycemia awareness was self-estimated by a validated method (14) that is recommended in the Danish guidelines for treatment of type 1 diabetes issued by the National Board of Health (15). Patients were recruited for participation in a cross-sectional survey from November 2011 to May 2013 and completed a questionnaire composed of validated questions on hypoglycemia after ensuring a common understanding of the questions and definitions used (12). The patients were informed that the data remain confidential and anonymized following incorporation into a database according to Danish data legislation. The core question was “How many episodes of severe hypoglycemia needing treatment assistance from another person have you had during the last year?” This definition of severe hypoglycemia is in accordance with the recommendations by the American Diabetes Association Workgroup on Hypoglycemia (16) and the recall within 1 year is well preserved and proven valid (14). Subsequently, medical records were scrutinized for occurrence of severe hypoglycemia in the 2 years before (2010 and 2011) and the year following (2012) implementation of EU regulations on driver’s licensing. Outpatient clinic data on severe hypoglycemia has been systematically collected (consistently using the same definition as above) at each 3- to 4-monthly visit during the last decade. The question posed to the patient as an integrated part of the consultation is “How many episodes of severe hypoglycemia needing treatment assistance from another person have you had since your last visit?” The number is documented on the diabetes summary chart. This practice has not been subject to changes during the study period. Mean
HbA1c level and insulin regimen and dose were also extracted for each of the calendar years: 2010, 2011, and 2012. Statistics
The sample size was aimed to be in the range of that of previous studies of severe hypoglycemia in cohorts of type 1 diabetic patients yielding robust results (14,17–20). Rates of severe hypoglycemia are given as mean (range). Other values shown in the text and tables are mean (SD) or n (%). Data coverage for each year is calculated as percentage of the year covered by valid data. Yearly rates of severe hypoglycemia are corrected for data completeness. Standard descriptive and comparative statistics are used as appropriate. Rates of severe hypoglycemia are compared by Wilcoxon signed ranks test. RESULTS
The baseline clinical characteristics of the participants are shown in Table 1. The proportion of subjects with risk factors for severe hypoglycemia such as hypoglycemia unawareness (13.9%) and undetectable C-peptide concentration (75.1%) are as expected in a representative random sample of patients with type 1 diabetes (12,13). From a mean yearly rate of severe hypoglycemic events in the medical records of 0.42 (0–6.5) events per patientyear in 2010 to 2011, the rate in 2012 was reduced by 55% to 0.19 (0–5) events per patient-year (P = 0.034) (Table 2 and Fig. 1). This was predominantly due to a 73% relative reduction in the proportion of subjects reporting recurrent (two or more) episodes (absolute reduction from 5.6 to 1.5% [P = 0.014]), whereas the number of subjects reporting solitary episodes within each calendar year was not significantly reduced (P = 0.88) (Fig. 2). There was no difference in reporting patterns between the sexes, and the decline in reporting was not associated with age or with hypoglycemia awareness class (not shown). The mean HbA 1 c level of 8.0% (1.1%) (64 [12] mmol/mol) in 2010 was reduced to 7.7% (1.0) (61 [11] mmol/mol) in 2012 (P = 0.035) (Table 2). There was a significant reduction of data coverage from 2010 to 2011 (P , 0.001), but no difference between 2011 and 2012 (Table 2). A number of patients were transferred to insulin analogs,
care.diabetesjournals.org
Pedersen-Bjergaard and Associates
Table 1—Baseline characteristics Demographics and clinical characteristics
n = 309
Women
118 (38.2)
Age (years)
52.4 (13.9)
Duration of diabetes (years)
23 (14)
Retinopathy
169 (54.7)
Nephropathy
41 (13.3)
BMI (kg/m2)
25.5 (4.0)
Hypertension
76 (24.6)
C-peptide negative Hypoglycemia awareness Normal Impaired Unaware Missing
232 (75.1) 133 (43.0) 130 (42.1) 43 (13.9) 3 (1.0)
Severe hypoglycemia (events per patient-year) Mean rate Range
0.63 0–15
Data are presented as mean (SD) or n (%) unless otherwise indicated.
and the number of patients on continuous subcutaneous insulin infusion (CSII) increased from 28 to 49 (P = 0.014) (Table 2). Exclusion of subjects commencing CSII therapy did not affect the annually reported rates of severe hypoglycemia significantly. The rate of 0.19 (0–5) episodes per patient-year reported in the medical records in 2012 was 70% lower than the annual rate of severe hypoglycemia of 0.63 (0–15) episodes per patient-year obtained in the questionnaire survey (P , 0.001) (Fig. 1). The main reason for this difference is a more than sevenfold higher proportion of subjects reporting recurrent episodes in the questionnaire (11.4 vs. 1.5%; P =
0.0046) (Fig. 2). There was no difference between the proportions reporting solitary events (P = 0.48). The difference between study reporting and clinic reporting was not associated with sex, age, or awareness class (not shown). CONCLUSIONS
This study demonstrates an immediate halving in reporting of severe hypoglycemia in a routine clinical setting following implementation of new EU regulations on driver’s licensing. The reduction was not explained by relaxation of metabolic control or by any specific intervention in the cohort, and therefore, it is probably not a true rate reduction. This is further supported by the
Table 2—Temporal development in rates of severe hypoglycemia as indicated in medical records, HbA1c levels, and insulin treatment regimens Year 2010
2011
2012
Data coverage (%)
81.7
65.4
66.1
Severe hypoglycemia Mean rate per patient-year Range
0.36 0–7
0.47 0–11
0.19 0–5
Insulin doses (IU/day)
51.2 (22.0)
49.8 (21.9)
49.5 (22.1)
Insulin regimen Analog basal-bolus Human basal-bolus Mixed basal-bolus CSII Other
113 (36.6) 48 (15,5) 55 (17.8) 28 (9.1) 65 (21.0)
125 (40.5) 46 (14.9) 48 (15.5) 38 (12.3) 52 (16.8)
128 (41.4) 41 (13.3) 55 (17.8) 49 (15.9) 36 (11.6)
HbA1c (%)
8.0 (1.1)
7.8 (1.1)
7.7 (1.0)
HbA1c (mmol/mol)
64 (12)
62 (12)
61 (11)
Data are presented as mean (SD) or n (%) unless otherwise indicated.
fact that the rate of severe hypoglycemia in the general type 1 diabetic population has only declined marginally during the past decades despite the introduction of a range of new therapeutic measures (12–14,17–20). The reduction was primarily due to a pronounced decline in the proportion of patients reporting recurrent events. This is noteworthy because a key operational point in the new EU regulations is that occurrence of two or more episodes of severe hypoglycemia within 12 months imposes withdrawal of driver’s licensing (10,11). This particular issue has been heavily debated in the mass media, with major contributions from the Danish Diabetes Association, and is presumably common knowledge to all patients with diabetes. In accordance, a recent Danish survey exploring the reluctance to report severe hypoglycemia by patients with type 1 diabetes reported that more than one-third of patients holding a driver’s licensedin particular, those prone to severe hypoglycemiad would consider keeping the episodes for themselves if their license would be endangered by reporting (21). Anonymous reporting may encourage some patients to report more accurate numbers of events. This was apparent by a threefold higher rate of severe hypoglycemia in the questionnaire survey when compared with that retrieved from the medical records. Again, the difference was almost exclusively due to different reporting of recurrent episodes. A previous large Danish anonymous survey in 2006 (13) included 500 consecutive patients from our clinic with clinical characteristics comparable to those of the actual cohort and yielded a rate of severe hypoglycemia of 0.86 episodes per patient-year (unpublished data from Kristensen et al. [13]), thus somewhat higher compared with the 0.63 episodes per patient-year in this study. The difference may be accounted for by systematic efforts in the clinic to reduce the rate, but a bias introduced by the driver’s licensing legislation on willingness to participate in a survey on hypoglycemia or on reportingd although anonymousdcannot be excluded. Finally, even patients’ own anonymous estimates in studies may be subject to underreporting, as rates of severe hypoglycemia obtained from spouses are often significantly higher
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Driver’s License and Reporting of Hypoglycemia
Diabetes Care
Figure 1—Mean annual rates of severe hypoglycemia obtained in an anonymous questionnaire survey and from medical records before and after the 1 January 2012 implementation of new EU legislation on driver’s licensing in Denmark.
than those reported by the patients (22,23). The study is strengthened by the thorough routine collection of hypoglycemic data in this clinic but, on the other hand, limited by not having a true prospective design. A reluctance to ask about and document severe hypoglycemia may include some health care professionals due to a misunderstood empathy for the patients. The potential impact of the latter cannot be estimated from the study, but the fact that data completeness was similar in 2011 and 2012 is argument against a major contribution. The clinical characteristics of the
participants and the rate of severe hypoglycemia in our clinic obtained under similar study conditions are comparable to those of other clinics (12,13), and consequently, the results are likely to be generalizable. The study shows that the estimated proportion of concealed severe hypoglycemia has now grown to approximately two-thirds of all episodes. There are several potential risks of such a burden of hidden severe hypoglycemia. At the individual patient level, this precludes from rational intervention against recurrent severe hypoglycemia. Facing a patient with recurrent
Figure 2—Proportion of patients with solitary and recurrent (two or more) episodes of severe hypoglycemia in an anonymous questionnaire (left columns) and as documented in the medical records in 2010, 2011, and 2012. SH, severe hypoglycemia.
severe hypoglycemia, a number of specific interventions may be considered: lifestyle intervention, including snacking and intensified self-monitoring; relaxation of glycemic target; changing insulin regimen; optimizing the use of bolus insulin, including carbohydrate counting; specific interventions for improvement of hypoglycemia awareness; and use of technology in terms of CSII and/or continuous glucose monitoring (24–27). By not being offered these opportunities, the patient may remain at continued risk of recurrent severe hypoglycemia and its consequences in terms of risk of accidents and reduced quality of life (1). As for the society, incremental concealed severe hypoglycemia may increase the risk of hypoglycemia-related traffic accidents. This may in fact be an unintended paradoxical result of the EU legislation as it stands. According to several surveys, ;20% of all type 1 diabetic patients will at a given time be at danger of revoked driver’s license (12,13). A reanalysis of data from the Diabetes Control and Complications Trial (DCCT)d which specifically excluded subjects with recurrent severe hypoglycemiad estimated that up to 30% of the participants would have had their license revoked at some time during the trial (28). Thus a very large proportion of patients with type 1 diabetes faces the risk of further stigmatization and may be tempted not to report recurrent severe hypoglycemia to their health care providers. For the benefit of the treatment of type 1 diabetes as well as traffic safety, it can be argued that granting of driver’s licensing should rely more on an individual risk assessment, as also recommended by the American Diabetes Association (2), including a documentation of proper self-care (self-monitoring and snacking) when driving, rather than operate on reported occurrence of severe hypoglycemia that is not a valid measure when the driver’s license is endangered. In conclusion, rates of severe hypoglycemia reported by patients with type 1 diabetes in routine clinical practice are immediately halved following implementation of the new EU directive on driver’s licensing. We acknowledge the importance of legislation on driver’s licensing because hypoglycemia impairs driving capacity (4–7). However, the recently altered Danish legislation seems to impose a threat against maintenance
care.diabetesjournals.org
of the physician-patient relationship necessary to improve long-term outcomes. Information about severe hypoglycemia in medical records only represent the tip of the iceberg, and it is therefore of utmost importance to improve the dialogue with the patients about this major clinical problem and its prevention.
Acknowledgments. The authors thank re-
search nurses Tove Larsen, Pernille Banck, and Charlotte Hansen, Department of Cardiology, Nephrology, and Endocrinology, Nordsjællands University Hospital Hillerød, for data collection and management. Funding. The study was funded by a grant from the Research Foundation of Nordsjællands University Hospital Hillerød, the Beckett Foundation, and the Foundation of Captain Lieutenant Harald Jensen and Wife. B.T. received core funding from Nordsjællands University Hospital Hillerød. Duality of Interest. U.P.-B. served on advisory boards for AstraZeneca/Bristol Myers Squibb and Novo Nordisk and received lecture fees from AstraZeneca/Bristol Myers Squibb, Sanofi Aventis, and Novo Nordisk. L.F. is now employed by Novo Nordisk. B.T. served on advisory boards for Eli Lilly. No other potential conflicts of interest relevant to this article were reported. Author Contributions. U.P.-B. initiated and designed the study, performed the data analysis, and drafted the first version of the manuscript. L.F. initiated and designed the study and participated in the collection of data. M.-L.A. and R.A. participated in the collection of data. B.T. initiated and designed the study. All authors have contributed to, read, and approved the final manuscript. U.P.-B. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented at the 74th Scientific Sessions of the American Diabetes Association, San Francisco, 13–17 June 2014.
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