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| Name | Class |
|---|---|
| University of Southern Denmark | OTHER |
| Sheffield Teaching Hospitals NHS Foundation Trust | OTHER |
| Cambridge University Hospitals NHS Foundation Trust | OTHER |
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Hypoglycaemia or low blood glucose, and its fear are major barriers to achieving optimal glucose control. New technology, such as continuous glucose monitors (CGM), help to better identify hypoglycaemia and develop strategies to avoid it. These devices measure glucose in the skin, rather than in the blood, and provide information not only on how low glucose is, but also for how long. Recent studies showed that over half of episodes of low glucose with these systems are not recognised by people with diabetes, and even people without diabetes have sensor values that are below the current thresholds for hypoglycaemia [ low blood glucose] that we measure with traditional monitors.
In this study, the investigators will evaluate the impact of symptomatic as well as asymptomatic episodes of low sensor glucose on a variety of clinical, patient-related and health economic outcomes such as mood, quality of sleep and productivity. The investigators will test different levels and durations of low sensor glucose to identify the one that best matches episodes that are symptomatic to best define hypoglycaemia using these systems.
The investigators will also look at factors that influence this such as sleep or activity as well as diabetes management behaviours (such as insulin dosing, carb counting, etc). At the end of this study, the investigators will be able to provide a better definition of clinically relevant low sensor glucose readings that will help inform clinical as well as academic interpretation of CGM data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| T1DM and intact awareness of hypoglycaemia | 200 participants with T1DM and intact awareness of hypoglycaemia |
| |
| T1Dm and impaired awareness of hypoglycaemia | 50 participants with T1Dm and impaired awareness of hypoglycaemia |
| |
| insulin treated T2DM | 350 participants with insulin treated T2DM ( > 1 injections / day) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NO intervention - observational study | Other | NO intervention - observational study |
|
| Measure | Description | Time Frame |
|---|---|---|
| LIG optimum detection of hypoglycemia | To determine the Low Interstitial Glucose (LIG) parameters that have the optimum performance for detection and identification of patient-reported-hypoglycemia (PRH); 〖LIG〗_PRH (h_opt,t_opt). | week 10 |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary outcome 1 | To evaluate the impact of symptomatic and asymptomatic hypoglycaemia on different domains of Quality of Life (QoL) and health economic variables measured by a bespoke mobile phone application. We will use the definition of LIG identified in the primary objective, 〖LIG〗_PRH (h_opt,t_opt), to evaluate the impact of symptomatic and asymptomatic hypoglycaemia on various outcome variables. To do this, we will divide the days into one of 4 categories LIG-PRH- :no hypoglycaemia LIG+PRH- :asymptomatic biochemical hypoglycaemia ( CGM false positive) LIG+PRH+ :symptomatic biochemical hypoglycaemia LIG-PRH+ :symptomatic without biochemical hypoglycaemia (CGM false negative) We will then compare the scores in different domains collected on the app ( eg reported mood, quality of sleep, alertness, productivity, time off work) between the 4 categories. |
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Inclusion Criteria:
Exclusion Criteria:
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A total of 600 participants will be recruited in the following categories.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| King's College London | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38512385 | Derived | Martine-Edith G, Zaremba N, Divilly P, Soholm U, Broadley M, Baumann PM, Mahmoudi Z, Gomes M, Ali N, Abbink EJ, de Galan B, Brosen J, Pedersen-Bjergaard U, Vaag AA, McCrimmon RJ, Renard E, Heller S, Evans M, Cigler M, Mader JK, Amiel SA, Speight J, Pouwer F, Choudhary P. Associations Between Hypoglycemia Awareness Status and Symptoms of Hypoglycemia Among Adults with Type 1 or Insulin-Treated Type 2 Diabetes Using the Hypo-METRICS Smartphone Application. Diabetes Technol Ther. 2024 Aug;26(8):566-574. doi: 10.1089/dia.2023.0596. Epub 2024 Apr 12. | |
| 38386436 |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003924 | Diabetes Mellitus, Type 2 |
| D007003 | Hypoglycemia |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Ninewells Hospital |
| OTHER |
| Radboud University Medical Center | OTHER |
| Nordsjaellands Hospital | OTHER |
| Medical University of Graz | OTHER |
| University Hospital, Montpellier | OTHER |
| Innovative Medicines Initiative | OTHER |
| The Leona M. and Harry B. Helmsley Charitable Trust | OTHER |
| Juvenile Diabetes Research Foundation | OTHER |
| International Diabetes Federation | OTHER |
| Novo Nordisk A/S | INDUSTRY |
| Abbott Diabetes Care | INDUSTRY |
| Medtronic MiniMed, Inc. | INDUSTRY |
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| week 10 |
| Secondary outcome 2 | To evaluate the impact of adding co-variates such as change of glucose for 30 minutes prior to the event and area under the curve to the threshold and duration parameters to see if this can improve the sensitivity and specificity of 〖LIG〗_PRH (h_opt,t_opt), | week 10 |
| Secondary outcome 3 | To evaluate the impact on these optimal parameters [〖LIG〗_PRH (h_opt,t_opt ] on Type of diabetes ( Type 1 with normal awareness, Type 2, Type 1 with impaired awareness) Awake vs sleeping ( as determined by Fitbit) Usual Mode of glucose monitoring (SMBG vs Flash vs CGM) Rate of 〖LIG〗_PRH during the study | week 10 |
| Secondary outcome 4 | To evaluate the impact of the rate of 〖LIG〗_PRH over the whole study duration on Rate of Patient reported hypoglycaemia ( non-severe) Rate of severe hypoglycaemia Overall EQ-5D-5L scores WPAI ( productivity) PROMIS - (sleep quality) Hypo fear scores Baseline C-peptide levels | week 10 |
| Secondary outcome 5 | To determine the parameters (threshold and duration) of low interstitial glucose (LIG) that best identify a pre-specified reduction/ change in QoL. [ 0.07 reduction in EQ-5D-5L] 〖LIG〗_(EQ-5D) (h_opt,t_opt). | week 10 |
| Secondary outcome 6 | To determine the parameters ( threshold and duration) of low interstitial glucose (LIG) that best identify a pre-specified health economic outcome. [1.5 hour loss of effective work/ activity] 〖LIG〗_productivity (h_opt,t_opt). | week 10 |
| Secondary outcome 7 | Determining the predictors of 〖LIG〗_PRH by looking at variables such as mean glucose, variability, activity (step count and intensity). | week 10 |
| Secondary outcome 8 | We will evaluate the impact of activity ( step count) on the risk of 〖LIG〗_PRH the following night. A generalized linear mixed models (GLMM) with step count as the independent variable and the rate of LIG_PRH as the response variable will address this research question | week 10 |
| Secondary outcome 9 | We will try to understand some of the causes of hypoglycaemia. To do this we will look at the 4 hours prior to every available 〖LIG〗_PRH (h_opt,t_opt) and PRH and describe the category of events (if also insulin data is available) by classifying them into those with Bolus within range [ < 10 mmol/l] within 4 hours Bolus and correction [ > 10 mmol/l ] within 4 hours No bolus within 4 hours Activity [ as identified by the Fitbit charge 3] within 2 hours. | week 10 |
| Secondary outcome 10 | Evaluating the effect of personality (assessed by DS-14) on number and severity of hypoglycaemia and the effect of hypoglycaemia on quality of life measures | week 10 |
| Derived |
| Martine-Edith G, Divilly P, Zaremba N, Soholm U, Broadley M, Baumann PM, Mahmoudi Z, Gomes M, Ali N, Abbink EJ, de Galan B, Brosen J, Pedersen-Bjergaard U, Vaag AA, McCrimmon RJ, Renard E, Heller S, Evans M, Cigler M, Mader JK, Speight J, Pouwer F, Amiel SA, Choudhary P, Hypo-Resolve FT. A Comparison of the Rates of Clock-Based Nocturnal Hypoglycemia and Hypoglycemia While Asleep Among People Living with Diabetes: Findings from the Hypo-METRICS Study. Diabetes Technol Ther. 2024 Jul;26(7):433-441. doi: 10.1089/dia.2023.0522. Epub 2024 Apr 17. |
| 35633291 | Derived | Divilly P, Zaremba N, Mahmoudi Z, Soholm U, Pollard DJ, Broadley M, Abbink EJ, de Galan B, Pedersen-Bjergaard U, Renard E, Evans M, Speight J, Brennan A, McCrimmon RJ, Mullenborn M, Heller S, Seibold A, Mader JK, Amiel SA, Pouwer F, Choudhary P; Hypo-RESOLVE Consortium. 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. |
| 35105572 | Derived | Soholm U, Broadley M, Zaremba N, Divilly P, Nefs G, Mahmoudi Z, de Galan B, Pedersen-Bjergaard U, Brennan A, Pollard DJ, McCrimmon RJ, A Amiel S, Hendrieckx C, Speight J, Choudhary P, Pouwer F; Hypo-RESOLVE Consortium. 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. BMJ Open. 2022 Feb 1;12(2):e051651. doi: 10.1136/bmjopen-2021-051651. |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |