Investigating the day-to-day impact of hypoglycaemia in adults with type 1 or type 2 diabetes: design and validation protocol of the Hypo-METRICS application

Uffe Søholm, Melanie Broadley, Natalie Zaremba, Patrick Divilly, Giesje Nefs, Zeinab Mahmoudi, Bastiaan de Galan, Ulrik Pedersen-Bjergaard, Alan Brennan, Daniel John Pollard, Rory J McCrimmon, Stephanie A Amiel, Christel Hendrieckx, Jane Speight, Pratik Choudhary, Frans Pouwer, Hypo-RESOLVE Consortium, Uffe Søholm, Melanie Broadley, Natalie Zaremba, Patrick Divilly, Giesje Nefs, Zeinab Mahmoudi, Bastiaan de Galan, Ulrik Pedersen-Bjergaard, Alan Brennan, Daniel John Pollard, Rory J McCrimmon, Stephanie A Amiel, Christel Hendrieckx, Jane Speight, Pratik Choudhary, Frans Pouwer, Hypo-RESOLVE Consortium

Abstract

Introduction: Hypoglycaemia is a frequent adverse event and major barrier for achieving optimal blood glucose levels in people with type 1 or type 2 diabetes using insulin. The Hypo-RESOLVE (Hypoglycaemia-Redefining SOLutions for better liVEs) consortium aims to further our understanding of the day-to-day impact of hypoglycaemia. The Hypo-METRICS (Hypoglycaemia-MEasurement, ThResholds and ImpaCtS) application (app) is a novel app for smartphones. This app is developed as part of the Hypo-RESOLVE project, using ecological momentary assessment methods that will minimise recall bias and allow for robust investigation of the day-to-day impact of hypoglycaemia. In this paper, the development and planned psychometric analyses of the app are described.

Methods and analysis: The three phases of development of the Hypo-METRICS app are: (1) establish a working group-comprising diabetologists, psychologists and people with diabetes-to define the problem and identify relevant areas of daily functioning; (2) develop app items, with user-testing, and implement into the app platform; and (3) plan a large-scale, multicountry study including interviews with users and psychometric validation. The app includes 7 modules (29 unique items) assessing: self-report of hypoglycaemic episodes (during the day and night, respectively), sleep quality, well-being/cognitive function, social interactions, fear of hypoglycaemia/hyperglycaemia and work/productivity. The app is designed for use within three fixed time intervals per day (morning, afternoon and evening). The first version was released mid-2020 for use (in conjunction with continuous glucose monitoring and activity tracking) in the Hypo-METRICS study; an international observational longitudinal study. As part of this study, semistructured user-experience interviews and psychometric analyses will be conducted.

Ethics and dissemination: Use of the novel Hypo-METRICS app in a multicountry clinical study has received ethical approval in each of the five countries involved (Oxford B Research Ethics Committee, CMO Region Arnhem-Nijmegen, Ethikkommission der Medizinischen Universität Graz, Videnskabsetisk Komite for Region Hovedstaden and the Comite Die Protection Des Personnes SUD Mediterranne IV). The results from the study will be published in peer review journals and presented at national and international conferences.

Trial registration number: NCT04304963.

Keywords: diabetes & endocrinology; general diabetes; health economics; information technology; mental health.

Conflict of interest statement

Competing interests: UPB has received grants and personal fees from Novo Nordisk and personal fees from AstraZeneca, Bristol-Meyers Squibb, Sanofi and Zealand Pharma.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Conceptual framework of the key areas of daily functioning that might be impacted by hypoglycaemia.
Figure 2
Figure 2
Sample of screenshots of the Hypoglycaemia—MEasurement, ThResholds and ImpaCtS app on the uMotif Limited platform.

References

    1. Leonard CE, Han X, Brensinger CM, et al. . Comparative risk of serious hypoglycemia with oral antidiabetic monotherapy: a retrospective cohort study. Pharmacoepidemiol Drug Saf 2018;27:9–18. 10.1002/pds.4337
    1. Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol 2014;10:711–22. 10.1038/nrendo.2014.170
    1. Little SA, Leelarathna L, Barendse SM, et al. . Severe hypoglycaemia in type 1 diabetes mellitus: underlying drivers and potential strategies for successful prevention. Diabetes Metab Res Rev 2014;30:175–90. 10.1002/dmrr.2492
    1. Fidler C, Elmelund Christensen T, Gillard S. Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ 2011;14:646–55. 10.3111/13696998.2011.610852
    1. Ahammed A, Pathan F, Afsana F, et al. . The burden of severe hypoglycemia on quality of life among diabetes mellitus patients in a tertiary level hospital of Bangladesh. Indian J Endocrinol Metab 2018;22:499–504. 10.4103/ijem.IJEM_338_17
    1. Davis RE, Morrissey M, Peters JR, et al. . Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes. Curr Med Res Opin 2005;21:1477–83. 10.1185/030079905X61929
    1. Rombopoulos G, Hatzikou M, Latsou D, et al. . The prevalence of hypoglycemia and its impact on the quality of life (QOL) of type 2 diabetes mellitus patients (the HYPO study). Hormones 2013;12:550–8. 10.14310/horm.2002.1443
    1. Green AJ, Fox KM, Grandy S, et al. . Self-Reported hypoglycemia and impact on quality of life and depression among adults with type 2 diabetes mellitus. Diabetes Res Clin Pract 2012;96:313–8. 10.1016/j.diabres.2012.01.002
    1. Lopez JM, Annunziata K, Bailey RA, et al. . Impact of hypoglycemia on patients with type 2 diabetes mellitus and their quality of life, work productivity, and medication adherence. Patient Prefer Adherence 2014;8:683–92. 10.2147/PPA.S58813
    1. Polonsky WH, Fisher L, Hessler D. The impact of non-severe hypoglycemia on quality of life in patients with type 2 diabetes. J Diabetes Complications 2018;32:373–8. 10.1016/j.jdiacomp.2018.01.014
    1. International Hypoglycaemia Study Group . Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol 2019;7:385–96. 10.1016/S2213-8587(18)30315-2
    1. Hendrieckx C, Halliday JA, Bowden JP, et al. . Severe hypoglycaemia and its association with psychological well-being in Australian adults with type 1 diabetes attending specialist tertiary clinics. Diabetes Res Clin Pract 2014;103:430–6. 10.1016/j.diabres.2013.12.005
    1. Khunti K, Alsifri S, Aronson R, et al. . Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes. Diabetes Res Clin Pract 2017;130:121–9. 10.1016/j.diabres.2017.05.004
    1. Shafiee G, Mohajeri-Tehrani M, Pajouhi M, et al. . The importance of hypoglycemia in diabetic patients. J Diabetes Metab Disord 2012;11:17. 10.1186/2251-6581-11-17
    1. Pedersen-Bjergaard U, Alsifri S, Aronson R, et al. . Comparison of the HAT study, the largest global hypoglycaemia study to date, with similar large real-world studies. Diabetes Obes Metab 2019;21:844–53. 10.1111/dom.13588
    1. Tan NC, Goh S-Y, Khoo EY-H, et al. . Self-Reported hypoglycaemia in insulin-treated patients with diabetes mellitus: results from the Singapore cohort of the International operations hypoglycaemia assessment tool study. Singapore Med J 2020;61:129–36. 10.11622/smedj.2019081
    1. Blome C, Augustin M. Measuring change in quality of life: bias in prospective and retrospective evaluation. Value Health 2015;18:110–5. 10.1016/j.jval.2014.10.007
    1. Shiffman S, Stone AA, Hufford MR. Ecological momentary assessment. Annu Rev Clin Psychol 2008;4:1–32. 10.1146/annurev.clinpsy.3.022806.091415
    1. Henriksen MM, Andersen HU, Thorsteinsson B, et al. . Asymptomatic hypoglycaemia in type 1 diabetes: incidence and risk factors. Diabet Med 2019;36:62–9. 10.1111/dme.13848
    1. Berkman ET, Giuliani NR, Pruitt AK. Comparison of text messaging and paper-and-pencil for ecological momentary assessment of food craving and intake. Appetite 2014;81:131–7. 10.1016/j.appet.2014.06.010
    1. de Galan BE, McCrimmon RJ, Ibberson M, et al. . Reducing the burden of hypoglycaemia in people with diabetes through increased understanding: design of the hypoglycaemia redefining solutions for better liVEs (Hypo-RESOLVE) project. Diabet Med 2020;37:1066–73. 10.1111/dme.14240
    1. Speight J, Reaney MD, Barnard KD. Not all roads lead to Rome-a review of quality of life measurement in adults with diabetes. Diabet Med 2009;26:315–27. 10.1111/j.1464-5491.2009.02682.x
    1. Billington R, et al. . The New Zealand World Health organization quality of life (WHOQOL) group. Vol. 123, 2010: 65–70.
    1. Biggers A, Sharp LK, Nimitphong H, et al. . Relationship between depression, sleep quality, and hypoglycemia among persons with type 2 diabetes. J Clin Transl Endocrinol 2019;15: :62–4. 10.1016/j.jcte.2018.12.007
    1. Brod M, Christensen T, Bushnell DM. Impact of nocturnal hypoglycemic events on diabetes management, sleep quality, and next-day function: results from a four-country survey. J Med Econ 2012;15:77–86. 10.3111/13696998.2011.624144
    1. Hayashino Y, Tsujii S, Ishii H, et al. . High frequency of non-nocturnal hypoglycemia was associated with poor sleep quality measure by Pittsburg sleep quality index in patients with diabetes receiving insulin therapy: diabetes distress and care registry at Tenri (DDCRT 4). Exp Clin Endocrinol Diabetes 2013;121:628–34. 10.1055/s-0033-1355424
    1. Martyn-Nemeth P, Phillips SA, Mihailescu D, et al. . Poor sleep quality is associated with nocturnal glycaemic variability and fear of hypoglycaemia in adults with type 1 diabetes. J Adv Nurs 2018;74:2373–80. 10.1111/jan.13765
    1. Gold AE, Deary IJ, Frier BM. Hypoglycaemia and non-cognitive aspects of psychological function in insulin-dependent (type 1) diabetes mellitus (IDDM). Diabet Med 1997;14:111–8. 10.1002/(SICI)1096-9136(199702)14:2<111::AID-DIA309>;2-S
    1. Geelhoed-Duijvestijn PH, Pedersen-Bjergaard U, Weitgasser R, et al. . Effects of patient-reported non-severe hypoglycemia on healthcare resource use, work-time loss, and wellbeing in insulin-treated patients with diabetes in seven European countries. J Med Econ 2013;16:1453–61. 10.3111/13696998.2013.852098
    1. Sommerfield AJ, Deary IJ, McAulay V, et al. . Short-Term, delayed, and working memory are impaired during hypoglycemia in individuals with type 1 diabetes. Diabetes Care 2003;26:390–6. 10.2337/diacare.26.2.390
    1. Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey in patients and physicians. Curr Med Res Opin 2012;28:1947–58. 10.1185/03007995.2012.743457
    1. Barendse S, Singh H, Frier BM, et al. . The impact of hypoglycaemia on quality of life and related patient-reported outcomes in type 2 diabetes: a narrative review. Diabet Med 2012;29:293–302. 10.1111/j.1464-5491.2011.03416.x
    1. Shi L, Shao H, Zhao Y, et al. . Is hypoglycemia fear independently associated with health-related quality of life? Health Qual Life Outcomes 2014;12:167. 10.1186/s12955-014-0167-3
    1. Singh H, Gonder-Frederick L, Schmidt K, et al. . Assessing hyperglycemia avoidance in people with type 1 diabetes. Diabetes Manag 2014;4:263–71. 10.2217/dmt.14.3
    1. Vanstone M, Rewegan A, Brundisini F, et al. . Patient perspectives on quality of life with uncontrolled type 1 diabetes mellitus: a systematic review and qualitative Meta-synthesis. Ont Health Technol Assess Ser 2015;15:1–29.
    1. Brod M, Christensen T, Thomsen TL, et al. . The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value Health 2011;14:665–71. 10.1016/j.jval.2011.02.001
    1. Dickinson JK, Guzman SJ, Maryniuk MD, et al. . The use of language in diabetes care and education. Diabetes Educ 2017;43:551–64. 10.1177/0145721717735535
    1. Speight J, Conn J, Dunning T, et al. . Diabetes Australia position statement. A new language for diabetes: improving communications with and about people with diabetes. Diabetes Res Clin Pract 2012;97:425–31. 10.1016/j.diabres.2012.03.015
    1. Eldar E, Rutledge RB, Dolan RJ, et al. . Mood as representation of momentum. Trends Cogn Sci 2016;20:15–24. 10.1016/j.tics.2015.07.010
    1. Rosenkranz T, Takano K, Watkins ER, et al. . Assessing repetitive negative thinking in daily life: development of an ecological momentary assessment paradigm. PLoS One 2020;15:e0231783. 10.1371/journal.pone.0231783
    1. Eisele G, Vachon H, Lafit G, et al. . The effects of sampling frequency and questionnaire length on perceived burden, compliance, and Careless responding in experience sampling data in a student population. Assessment 2020:1073191120957102. 10.1177/1073191120957102
    1. Silvia PJ, Kwapil TR, Walsh MA, et al. . Planned missing-data designs in experience-sampling research: Monte Carlo simulations of efficient designs for assessing within-person constructs. Behav Res Methods 2014;46:41–54. 10.3758/s13428-013-0353-y
    1. DeCastellarnau A. A classification of response scale characteristics that affect data quality: a literature review. Qual Quant 2018;52:1523–59. 10.1007/s11135-017-0533-4
    1. Emerson JA, Dunsiger S, Williams DM. Reciprocal within-day associations between incidental affect and exercise: an EMA study. Psychol Health 2018;33:130–43. 10.1080/08870446.2017.1341515
    1. Kratz AL, Murphy SL, Braley TJ. Ecological Momentary assessment of pain, fatigue, depressive, and cognitive symptoms reveals significant daily variability in multiple sclerosis. Arch Phys Med Rehabil 2017;98:2142–50. 10.1016/j.apmr.2017.07.002
    1. Engelen L, Held F. Understanding the office: using ecological Momentary assessment to measure activities, posture, social interactions, mood, and work performance at the workplace. Buildings 2019;9:54. 10.3390/buildings9020054
    1. uMotif . uMotif. Available: [Accessed 20 Jul 2020].
    1. Lakshminarayana R, Wang D, Burn D, et al. . Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson's disease. NPJ Parkinsons Dis 2017;3:2. 10.1038/s41531-016-0003-z
    1. Dixon WG, Beukenhorst AL, Yimer BB, et al. . How the weather affects the pain of citizen scientists using a smartphone APP. NPJ Digit Med 2019;2:105. 10.1038/s41746-019-0180-3
    1. Wild D, Grove A, Martin M, et al. . Principles of good practice for the translation and cultural adaptation process for patient-reported outcomes (pro) measures: report of the ISPOR Task force for translation and cultural adaptation. Value Health 2005;8:94–104. 10.1111/j.1524-4733.2005.04054.x
    1. Hypo-METRICS . Hypoglycaemia - Measurement, ThResholds and ImpaCtS (Hypo-METRICS), 2020. Available:
    1. Palmier-Claus JE, Myin-Germeys I, Barkus E, et al. . Experience sampling research in individuals with mental illness: reflections and guidance. Acta Psychiatr Scand 2011;123:12–20. 10.1111/j.1600-0447.2010.01596.x
    1. Reise SP, Ventura J, Nuechterlein KH, et al. . An illustration of multilevel factor analysis. J Pers Assess 2005;84:126–36. 10.1207/s15327752jpa8402_02
    1. Forkmann T, Spangenberg L, Rath D, et al. . Assessing suicidality in real time: a psychometric evaluation of self-report items for the assessment of suicidal ideation and its proximal risk factors using ecological momentary assessments. J Abnorm Psychol 2018;127:758–69. 10.1037/abn0000381
    1. Theobald E. Students are rarely independent: when, why, and how to use random effects in Discipline-Based education research. CBE Life Sci Educ 2018;17:rm2. 10.1187/cbe.17-12-0280
    1. Woyshville MJ, Lackamp JM, Eisengart JA, et al. . On the meaning and measurement of affective instability: clues from chaos theory. Biol Psychiatry 1999;45:261–9. 10.1016/S0006-3223(98)00152-8

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する