Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol

Patrick Divilly; Natalie Zaremba; Zeinab Mahmoudi; Uffe Søholm; Daniel J Pollard; Melanie Broadley; Evertine J Abbink; Bastiaan de Galan; Ulrik Pedersen-Bjergaard; Eric Renard; Mark Evans; Jane Speight; Alan Brennan; Rory J McCrimmon; Matthias Müllenborn; Simon Heller; Alexander Seibold; Julia K Mader; Stephanie A Amiel; Frans Pouwer; Pratik Choudhary; Hypo-RESOLVE Consortium

doi:10.1111/dme.14892

Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol

Diabet Med. 2022 Sep;39(9):e14892. doi: 10.1111/dme.14892. Epub 2022 Jun 22.

Authors

Patrick Divilly¹, Natalie Zaremba¹, Zeinab Mahmoudi^{1

2}, Uffe Søholm^{1

3}, Daniel J Pollard⁴, Melanie Broadley³, Evertine J Abbink⁵, Bastiaan de Galan^{5

6

7}, Ulrik Pedersen-Bjergaard^{8

9}, Eric Renard^{10

11}, Mark Evans¹², Jane Speight^{13

14}, Alan Brennan⁴, Rory J McCrimmon¹⁵, Matthias Müllenborn¹⁶, Simon Heller¹⁷, Alexander Seibold¹⁸, Julia K Mader^{19

20}, Stephanie A Amiel¹, Frans Pouwer^{3

21}, Pratik Choudhary^{1

22}; Hypo-RESOLVE Consortium

Affiliations

¹ Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
² Digital Therapeutics, Scientific Modelling, Novo Nordisk A/S, Søborg, Denmark.
³ Department of Psychology, University of Southern Denmark, Odense, Denmark.
⁴ School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
⁵ Department of internal medicine, Radboud university medical centre, Nijmegen, The Netherlands.
⁶ Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre, Maastricht, The Netherlands.
⁷ CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
⁸ Department of Endocrinology and Nephrology, Nordsjaellands Hospital Hillerød, Hillerød, Denmark.
⁹ Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, Montpellier, France.
¹¹ Institute of Functional Genomics, University of Montpellier, CNRS, INSERM, Montpellier, France.
¹² Wellcome Trust-MRC Institute of Metabolic Science and Department of Medicine, University of Cambridge, UK.
¹³ School of Psychology, Deakin University, Geelong, Australia.
¹⁴ The Australian Centre for Behavioural Research in Diabetes, Diabetes Victoria, Melbourne, Australia.
¹⁵ Systems Medicine, School of Medicine, University of Dundee, Dundee, UK.
¹⁶ Novo Nordisk A/S, Bagsvaerd, Denmark.
¹⁷ University of Sheffield, Sheffield, UK.
¹⁸ Abbott Diabetes Care, Wiesbaden, Germany.
¹⁹ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
²⁰ Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
²¹ Steno Diabetes Center Odense, Odense, Denmark.
²² Diabetes Research Centre, University of Leicester, Leicester, UK.

Abstract

Introduction: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia.

Methods: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes.

Ethics and dissemination: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations.

Trial registration: ClinicalTrials.gov NCT04304963.

Keywords: continuous glucose monitoring; hypoglycaemia; patient-reported hypoglycaemia; quality of life; sensor-detected.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benchmarking
Blood Glucose
Blood Glucose Self-Monitoring / methods
Diabetes Mellitus, Type 1* / complications
Diabetes Mellitus, Type 1* / drug therapy
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Glycated Hemoglobin / analysis
Humans
Hypoglycemia* / diagnosis
Hypoglycemic Agents / therapeutic use
Observational Studies as Topic
Quality of Life

Substances

Blood Glucose
Glycated Hemoglobin A
Hypoglycemic Agents

Associated data

ClinicalTrials.gov/NCT04304963