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• Letter to the editor regarding published article by de Groot et al. ‘A cost of illness study of hypoglycaemic events in insulin-treated diabetes in the Netherlands’
  Lisa Aniek de Jong, Lotte Westerink, Evgeni Dvortsin and Maarten Postma
  Published on: 21 August 2018

• Published on: 21 August 2018

  Letter to the editor regarding published article by de Groot et al. ‘A cost of illness study of hypoglycaemic events in insulin-treated diabetes in the Netherlands’

  • Lisa Aniek de Jong, PhD candidate pharmacoeconomics Unit of PharmacoTherapy, -Epidemiology & -Economics, University of Groningen, the Netherlands
  • Other Contributors:
    • Lotte Westerink, PhD candidate pharmacoeconomics
    • Evgeni Dvortsin, Health economist
    • Maarten Postma, Professor in pharmacoeconomics

  Dear editor,

  We would like to congratulate de Groot et al. for having performed this cost of illness study regarding hypoglycaemic events in insulin-treated diabetic patients in the Netherlands, which is a great step forward to a broader perspective on the hypoglycaemic burden specifically for the Netherlands [1]. In this study, Groot et al. use data from self-assessment questionnaires in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients in the Netherlands during a 4-week follow up period, to assess the costs of hypoglycaemic events. The article sheds light on the substantial impact which direct and indirect costs related to hypoglycaemia have on the total economic burden of diabetes. Accordingly, the study suggests that preventing hypoglycaemia can lead to an increase in quality of life, but also lead to a reduction in DM-related health care costs. We would like to elaborate on the results of this study to stimulate debate, and encourage further research.

  Using self-reported data on hypoglycaemic events due to insulin treatment, de Groot et al. estimated that the total annual costs of hypoglycaemia, lies between a range of €112.5 million to €590.8 million in the Netherlands. Further research could support the conclusions reached in this study, for example, using alternative sources and methods to estimate costs. In addition, further research could be conducted on the incidence and frequency of hypoglycaemia and its potential consequences. To furthe...

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  Dear editor,

  We would like to congratulate de Groot et al. for having performed this cost of illness study regarding hypoglycaemic events in insulin-treated diabetic patients in the Netherlands, which is a great step forward to a broader perspective on the hypoglycaemic burden specifically for the Netherlands [1]. In this study, Groot et al. use data from self-assessment questionnaires in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients in the Netherlands during a 4-week follow up period, to assess the costs of hypoglycaemic events. The article sheds light on the substantial impact which direct and indirect costs related to hypoglycaemia have on the total economic burden of diabetes. Accordingly, the study suggests that preventing hypoglycaemia can lead to an increase in quality of life, but also lead to a reduction in DM-related health care costs. We would like to elaborate on the results of this study to stimulate debate, and encourage further research.

  Using self-reported data on hypoglycaemic events due to insulin treatment, de Groot et al. estimated that the total annual costs of hypoglycaemia, lies between a range of €112.5 million to €590.8 million in the Netherlands. Further research could support the conclusions reached in this study, for example, using alternative sources and methods to estimate costs. In addition, further research could be conducted on the incidence and frequency of hypoglycaemia and its potential consequences. To further elucidate the total burden of hypoglycaemia in diabetic patients, additional data during an extended follow-up period could be collected to provide a more comprehensive view of hypoglycaemia related costs. Additional data could include hypoglycaemia related adverse events, such as: falls, fractures, and corresponding hospitalisations.

  Hypoglycaemia may cause dizziness, visual disturbances, confusion or even loss of consciousness in severe cases, which can lead to falls, and associated fractures, other injuries and hospitalizations [2–5]. To further elucidate the total burden of hypoglycaemia in diabetic patients, additional data during an extended follow-up period could be collected to provide a more comprehensive view of hypoglycaemia related costs. Furthermore, it is important to consider that 74% of T2DM patients in the Netherlands is 65-years or older [6]. Elderly T2DM patients often have multiple comorbidities and therefore polypharmacy, resulting in a higher rate of frailty. As such, fractures due to hypoglycaemia in T2DM patients may be frequent, and represent a significant adverse outcome with associated costs, in T2DM patients.

  A disadvantage of self-reported assessments used in the study by de Groot et al. is that these reports can only be completed by patients in an outpatient care setting. This means that ill, frail or non-ambulatory diabetes patients would be excluded from the self-report assessment, which eventually leads to partial mapping of the hypoglycaemia burden. Further research focussing on complications and hospitalizations due to hypoglycaemic events, would support the identification of additional consequences and costs that are part of the total burden of hypoglycaemia.

  The study by De Groot et al. focuses on insulin-treated T1DM and T2DM patients. The outcome of the study reflects the total burden of disease in T1DM patients in the Netherlands, as these patients are treated with insulin upon diagnosis. Nevertheless, only a proportion of patients with T2DM are actually treated with insulin. In the Netherlands insulin will only be prescribed to T2DM patients once oral treatment is insufficient, which means that prior to insulin, they have often already been treated with other drugs for years. Whereas many oral drugs are not related to hypoglycaemic risks, some oral treatments, like sulphonylurea derivatives, do have such risk [7]. Further research could evaluate the impact of these oral drugs on the economic burden of hypoglycaemia. As patients that use oral treatments are on average younger than patients on insulin, costs related to productivity losses could be measured alongside healthcare costs.

  De Groot et al. based the costs of hypoglycaemia on a subanalysis of the Global Hypoglycaemia Assessment Tool (HAT) study [8]. This subanalysis indicates that 15% of Dutch patients had a severe event, which is considered reasonably high compared to other international studies and guidelines [1]. For example, the Dutch primary care guideline for T2DM refers to Schopman et al., which mentions a lower incidence of severe hypoglycaemic events in T2DM [7,9]. Varying definitions for hypoglycaemia and severe hypoglycaemia could partially explain this difference. Notably, De Groot et al. defined a severe event as “hypoglycaemia requiring assistance from another person to administer carbohydrate and/or glucagon”(p.2), whereas Schopman et al. refer to a severe event as hypoglycaemia requiring help of a third party or medical assistance [1,9]. Consensus on the definition of a hypoglycaemic event, and a consistent application of this definition, can facilitate the identification of hypoglycaemia at a higher level of granularity and consistency. Furthermore, we would suggest to make a distinction between mild, moderate and severe events, following the definitions of the AACE/ACE guidelines [10]. These guidelines provide a clear definition of severity states, and are commonly used in international health economic studies.

  Considering our review and suggestions on the article of de Groot et al., we recommend that further research is conducted to help identify, broaden and complete the knowledge on the economic burden of hypoglycaemia in the Netherlands. This will require research that includes a longer follow-up period, the inclusion of T2DM patients that are not using insulin, and the application of a common definition and categorization of hypoglycaemia. Throughout the next four years, a recently launched EU project Hypo-RESOLVE aims to identify the burden of hypoglycaemia in Europe, including the Netherlands [11]. The start of this project underlines the critical need for more data and knowledge in this area, and the importance of the study published by de Groot et al. In the meantime, we would recommend performing additional analyses to assess the incidence of hypoglycaemic events and its consequences in terms of falls, fractures and hospitalizations as reported in different (Western) countries in T2DM patients, to complement the study of de Groot et al. This knowledge will further broaden the perspective and strengthen the evidence base of the total burden of hypoglycaemia for T2DM population in the Netherlands.

  References
  1. de Groot S, Enters-Weijnen CF, Geelhoed-Duijvestijn PH, Kanters TA. A cost of illness study of hypoglycaemic events in insulin-treated diabetes in the Netherlands. BMJ Open. 2018 Mar 25;8(3):e019864.
  2. Mattishent K, Loke YK. Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients. J Diabetes Complications. 2016 Jul;30(5):811–8.
  3. Pijpers E, Ferreira I, de Jongh RT, Deeg DJ, Lips P, Stehouwer CDA, et al. Older individuals with diabetes have an increased risk of recurrent falls: analysis of potential mediating factors: the Longitudinal Ageing Study Amsterdam. Age Ageing. 2012 May;41(3):358–65.
  4. Kachroo S, Kawabata H, Colilla S, Shi L, Zhao Y, Mukherjee J, et al. Association Between Hypoglycemia and Fall-Related Events in Type 2 Diabetes Mellitus: Analysis of a U.S. Commercial Database. J Manag Care Spec Pharm. 2015 Mar;21(3):243–53.
  5. Hartholt KA, Polinder S, Van der Cammen TJM, Panneman MJM, Van der Velde N, Van Lieshout EMM, et al. Costs of falls in an ageing population: A nationwide study from the Netherlands (2007–2009). Injury. 2012 Jul 1;43(7):1199–203.
  6. Dutch Institute for Public Health and Environment (RIVM). Volksgezondheid Toekomst Verkenning - Aandoeningen - Diabetes [Internet]. 2018 [cited 2018 Feb 21]. Available from: https://www.vtv2018.nl/aandoeningen
  7. Rutten G, De Grauw W, Nijpels G, Houweling S, Van de Laar F, Bilo H, et al. NHG-Standaard Diabetes mellitus type 2 (Vierde (partiële) herziening). Huisarts Wet [Internet]. 2018 [cited 2018 Feb 28]; Available from: https://www.nhg.org/standaarden/volledig/nhg-standaard-diabetes-mellitus...
  8. Khunti K, Alsifri S, Aronson R, Cigrovski Berković M, Enters-Weijnen C, Forsén T, et al. Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study. Diabetes Obes Metab [Internet]. 2016 Sep [cited 2018 Jun 5];18(9):907–15. Available from: http://doi.wiley.com/10.1111/dom.12689
  9. Schopman JE, Simon ACR, Hoefnagel SJM, Hoekstra JBL, Scholten RJPM, Holleman F. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2014 Jan;30(1):11–22.
  10. Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al. AACE/ACE Guidelines AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY – CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN – 2015 AACE TAsk ForCE For DEvEloping A DiAbETEs ComprEhEnsivE CArE plAn WriTing CommiTTEE. Endocr Pract Endocr Pr. 2015;21.
  11. Hypoglycaemia - REdefining SOLutions for better liVEs | Hypo-RESOLVE [Internet]. [cited 2018 Jun 5]. Available from: https://hypo-resolve.eu/

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  Conflict of Interest:
  None declared.

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