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, 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

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.

Conflict of interest statement

SAA has served on advisory boards for NovoNordisk and Medtronic and has spoken at an educational symposium sponsored by Sanofi. MLE has served on advisory boards and/or received lecture fees and/or research support from NovoNordisk, Eli Lilly, AstraZeneca, Medtronic, Dexcom, Ypsomed, Abbott Diabetes Care, Roche, NGM Pharma, Zucara, Pila Pharma. UPB has served on advisory boards and has received lecture fees from Sanofi and Novo Nordisk. JKM is a member in the advisory board of Boehringer Ingelheim, Eli Lilly, Medtronic, NovoNordisk AS, Prediktor A/S, Roche Diabetes Care, Sanofi‐Aventis and received speaker honoraria from Abbott Diabetes Care, Astra Zeneca, Dexcom, Eli Lilly, Medtronic, MSD, NovoNordisk AS, Roche Diabetes Care, Sanofi, Servier and Takeda. ER has served as a consultant/advisor for Abbott, Air Liquide SI, Astra‐Zeneca, Boehringer‐Ingelheim, Dexcom, Eli‐Lilly, Hillo, Insulet, Medirio, Novo‐Nordisk, Roche, Sanofi‐Aventis, Tandem, and received research support from Dexcom and Tandem. JS has served on advisory boards for Janssen, Medtronic, Roche Diabetes Care and Sanofi Diabetes; her research group (Australian Centre for Behavioural Research in Diabetes [ACBRD]) has received honoraria for this advisory board participation and has also received unrestricted educational grants and in‐kind support from Abbott Diabetes Care, AstraZeneca, Medtronic, Roche Diabetes Care and Sanofi Diabetes. JS has also received sponsorship to attend educational meetings from Medtronic, Roche Diabetes Care, and Sanofi Diabetes, and consultancy income or speaker fees from Abbott Diabetes Care, AstraZeneca, Medtronic, Novo Nordisk, Roche Diabetes Care and Sanofi Diabetes. PC has received personal fees Abbott Diabetes Care, Insulet, Dexcom, Novo Nordisk, AstraZeneca, Medtronic, Roche Diabetes Care and Sanofi Diabetes. Research funding support from Abbott Diabetes Care, Medtronic and Novo Nordisk.

© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Figures

FIGURE 1
FIGURE 1
Motif and check‐ins
FIGURE 2
FIGURE 2
Participant timeline for the study
FIGURE 3
FIGURE 3
A SDH defined by a threshold, h, and a minimum duration, t, under the threshold
FIGURE 4
FIGURE 4
Data visualization; Sensor glucose with step count and heart rate over time

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