CGM, Diabetes Mellitus Type 2, Infection
Conditions
Keywords
automated insulin delivery systems, AID, CGM, continouse glucose monitoring, infectiouse disease, type 2 diabetes mellitus, diabetes mellitus type 2, GlucoTab
Brief summary
Aim The investigators aim to investigate if automated insulin delivery systems (AID) improve in-hospital glycemic and clinical outcomes in patients with type 2 diabetes compared to standard-of-care with a pen-basal-bolus insulin regimen manually titrated by general staff at Herlev-Gentofte Hospital and a clinical decision support system (GlucoTab) titrating the basal-bolus regimen automatically daily at Graz University Hospital. Population Hospitalized patients with type 2 diabetes in non-intensive care units (non-ICU) at medical wards at Copenhagen University Hospitals of Herley-Gentofte (affiliated with Steno Diabetes Center Copenhagen) and Medical University Hospital of Graz (N = 92). Design This is an investigator-initiated, two-armed, two-site, prospective, randomized, open-label, blinded endpoint (PROBE) trial. Objectives The objective is to determine the glycemic and clinical effects of inpatient AID systems in non-ICU patients with type 2 diabetes. Participants will be randomized in a usual-of-care and an AID arm. Diabetes management will be performed by usual care in the control arm based on a basal-bolus insulin regimen and point-of-care (POC) glucose testing. A continuous glucose monitoring (CGM) system (Abbott FreeStyle Libre 3) will be used in all groups for outcome analysis and comparison between the groups. The CGM will be blinded for the control arm, to not interfere with the usual of care because of the higher amount of glucose data. The AID-arm will be managed by an AID system with real-time CGM data transmitted to nursing stations. Outcomes Primary outcome: The primary outcome is the difference in CGM-recorded time in range (TIR) (70-180 mg/dl (3.9-10.0 mmol/l)) between the POC- and the CGM-arm according to the 2023 in-hospital CGM consensus during the entire hospital stay. Secondary outcomes: Outcomes are reported according to the 2023 in-hospital CGM consensus and specified in the protocol during the entire hospital stay, including three levels of time above range (TAR) 180-250mg/dl (10.0-13.9 mmol/l), \>250mg/dl (\>13.9 mmol/l), and \>180mg/dl (\>10.0 mmol/l); three levels of time below range (TBR) 54-70mg/dl (3.0-3.9 mmol/l), \<54mg/dl (\<3.0 mmol/l), and \<70mg/dl (\<3.9 mmol/l); events of hypoglycemia in three levels, 54-68mg/dl (3.0-3.8 mmol/l), \<54mg/dl (\< 3.0 mmol/l), and \<70mg/dl (\<3.9 mmol/l), where the glucose values between the two hypoglycemic events must all be \>70mg/dl (\>3.9 mmol/l) for at least 15 consecutive minutes(1), including prolonged hypoglycemic events (\> 120 minutes), recurrent hypoglycemic events (events preceded by another hypoglycemic event), and recurrent hypoglycemic days (percentage of days with at least one hypoglycemic event on separate days that is preceded by another in-hospital day with hypoglycemia(1)); mean glucose level; standard deviation (SD) of the CGM glucose distribution; coefficient of variation (CV); and insulin doses during hospitalization. Clinical outcomes: The investigator assess the length of hospital stay as calculated from time of admission until discharge; in-hospital mortality; admissions to intensive care unit; any in-hospital-related complications occurring at least one day after randomization and until discharge, as documented and defined by the treating physician in the electronic health record (e.g., acute kidney injurie, sepsis, etc.) Method For the usual-of-care-arm, glucose assessment is done by standard POC glucose testing and insulin is manually titrated by general staff at Herlev-Gentofte Hospital and the glucose assessment is done by standard POC glucose testing and insulin is manually titrated by the GlucoTab system titrating the basal-bolus regimen automatically daily at Graz University Hospital. For the AID-arm, CGM data informs in real time the mylife Ypsopump for automated insulin delivery. Device The investigational device is the AID system, containing of the mylife YpsoPump and the FreeStyle Libre 3 sensor.
Interventions
To date, no randomized controlled trials have evaluated inpatient use - including bolus insulin - in patients with infectious disease.
PROCEDUREGlucoTab
Participants at Graz University Hospital are basal-bolus insulin regimen , however, insulin is not manually titrated, but titration is based daily on the GlucoTab system, a clinical decision support validated for the inpatient setting in titrating insulin for patients with type 2 diabetes as this is the usual of care at MUG. The GlucoTab-arm will be titrated initially by the principal Investigator or sub principal investigator and afterwards by the general ward nurses of MUG.
PROCEDUREControl-arm
In the control-arm, glucose levels are assessed with POC glucose testing at 03:00 h, pre-prandial at breakfast, lunch, and dinner, and before bedtime (22:00 h) or for participants not eating at 03:00 h, 08:00 h, 12:00 h, 17:00 h, and 22:00 h. Those collected glucose levels will be automatically transferred to the EHR. If POC glucose testing is not prescribed or performed five times daily as standard of care, the research staff may encourage usual ward nurses to do so. The investigat will also mount a FreeStyle Libre-3 CGM on each participant like descripted in the section above to be able to have a better comparison of the glucose levels throughout the day in both arms. This glucose data will be blinded and as such only be available for the diabetes research team in the end of the trial and not for the general wards. At admission, non-insulin antidiabetic medications will be paused, and the control-arm participants will be treated by usual-of-care with a pen based a basal-bolus regimen
Sponsors
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
The CGM-arm will be masked, the AID-arm will be open-label.
Intervention model description
This is an investigator-initiated, two-armed, two-site, prospective, randomized, open-label, blindedendpoint (PROBE) trial. The trial is conducted in general medical wards of Herlev-Gentofte Hospital (affiliated with Steno Diabetes Center Copenhagen) and Graz University Hospital (MUG), Austria.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A documented history of Type 2 diabetes mellitus (T2DM) which requires subcutaneous insulin therapy * acute infectious disease of any kind * age ≥ 18 years old * willingness and ability to comply with theclinical investigation plan * ability to communicate with the trial personal * an expected length of hospital stay for at least 2 days after enrolment
Exclusion criteria
* Patients already using AID for their glycemic management * Patients in use of an insulin pump * Skin pathologies that hinder application of a FreeStyle Libre-3 CGM and mylife YpsoPump * Participation in another trial, which could influence the outcome of the trial * Any mental condition rendering the patient incapable of giving informed consent * Known or suspected allergy to adhesive material/tape of the Libre-3-sensor and/or YpsoPump * Any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the patient * Diagnoses/treatments/clinical parameters prohibiting use of Insulin/AID such as * Estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m2 OR * Treated with hydroxyurea/hydroxycarbamide OR * Nutritional therapy (continuous enteral or parenteral feeding) OR * Clinically relevant pancreatic disease OR * Aystemic glucocorticoid treatment with prednisone equivalent dose \>5 mg/day OR * Expected to require admission to the intensive-care unit OR \> Patients in dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in range | From inclusion in the trial until discharge from hospital (up to 30 days) | The difference in CGM-recorded time in range of 70-180 mg/dl (3.9-10.0 mmol/l) between the control-arm and the AID-arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time above range level 1 | From inclusion in the trial until discharge from hospital (up to 30 days) | The difference in CGM-recorded time in range of 181 - 250 mg/dl (10.1 - 13.9 mmol/L) between the control-arm and the AID-arm |
| Time above range level 2 | From inclusion in the trial until discharge from hospital (up to 30 days) | The difference in CGM-recorded time in range of \> 250 mg/dl (\> 13.9 mmol/l between the control-arm and the AID-arm |
| Time below range level 1 | From inclusion in the trial until discharge from hospital (up to 30 days) | The difference in CGM-recorded time in the range of 54 - 70 mg/dl (3.0 - 3.9 mmol/L) between the control-arm and the AID-arm |
| Time below range level 2 | From inclusion in the trial until discharge from hospital (up to 30 days) | The difference in CGM-recorded time in the range of \< 54 mg/dl (\< 3.0 mmol/l) between the control-arm and the AID-arm |
| Hypoglycemic events level 1 | From inclusion in the trial until discharge from hospital (up to 30 days) | Hypoglycemic events (defined as three consecutive CGM measures) in the range of 54-70 mg/dl (3.0-3.9 mmol/l). |
| Hypoglycemic event level 2 | From inclusion in the trial until discharge from hospital (up to 30 days) | Hypoglycemic events (defined as three consecutive CGM measures) in the range of \<54 mg/dl (\<3.0 mmol/l). |
| Recurrent hypoglycemic event | From inclusion in the trial until discharge from hospital (up to 30 days) | Recurrent hypoglycemic events, defined as events preceded by another hypoglycemic event. The glucose values between the two episodes must all be \> 70mg/dl (\>3.9 mmol/l) for at least 15 consecutive minutes between the sentinel and recurrent hypoglycemic events to count. |
| Time at High Risk for Hypoglycemia | From inclusion in the trial until discharge from hospital (up to 30 days) | The difference in CGM-recorded time in range of 70 - 100 mg/dl (3.9 - 5.6 mmol/l) between the control-arm and the AID-arm |
| Glycemia risk index | From inclusion in the trial until discharge from hospital (up to 30 days) | Defined by the formula \[3.0 × % time below 54mg/dl (3.0 mmol/l)\] +\[2.4 × % time below 70mg/dl (3.9 mmol/l)\] + \[1.6 × % time above 180mg/dl (10.0 mmol/l)\] + \[0.8 × % time above 250mg/dl (13.9 mmol/l)\]. |
| Prolonged hypoglycemic events level 1 | From inclusion in the trial until discharge from hospital (up to 30 days) | A hypoglycaemic event 54 - 70 mg/dl (3.0 - 3.9 mmol/l) continuously for at least 120 minutes. |
| Prolonged hypoglycemic event level 2 | From inclusion in the trial until discharge from hospital (up to 30 days) | A hypoglycaemic event \<54 mg/dl (\<3.0 mmol/l) continuously for at least 120 minutes. |
| Severe hypoglycemia | From inclusion in the trial until discharge from hospital (up to 30 days) | Patient requires assistance to correct hypoglycemia. |
| Mean sensor glucose | From inclusion in the trial until discharge from hospital (up to 30 days) | Mean sensor glucose from the CGM in mg/dl (mmol/l). |
| Standard deviation of the glucose distribution | From inclusion in the trial until discharge from hospital (up to 30 days) | The standard deviation mg/dl (mmol/l) from the CGM glucose measurements. |
| Coefficient of variation | From inclusion in the trial until discharge from hospital (up to 30 days) | The standard deviation of the glucose distribution divided by the mean glucose level. |
| Length of stay | From admission untill discharge from the hospital (up to 30 days) | The amount of time spent in the hospital from admission untill discharge from the hospital |
| In-hospital complications | One day after randomisation until discharge from the hospital (up to 30 days) | Any in-hospital related complications occurring at least one day after randomization (e.g. acute kidney injury, sepsis, etc.) |
| Total daily insulin doses | From inclusion in the trial until discharge from hospital (up to 30 days) | The amoun of daily insulin given. |
Countries
Austria, Denmark
Outcome results
None listed