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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
92
To date, no randomized controlled trials have evaluated inpatient use - including bolus insulin - in patients with infectious disease.
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.
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
University Hospital of Graz
Graz, Styria, Austria
Steno Diabetes Center Copenhagen
Copenhagen, Denmark
Time in range
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
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Time above range level 1
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 frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Time above range level 2
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 frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Time below range level 1
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 frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Time below range level 2
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
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Hypoglycemic events level 1
Hypoglycemic events (defined as three consecutive CGM measures) in the range of 54-70 mg/dl (3.0-3.9 mmol/l).
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Hypoglycemic event level 2
Hypoglycemic events (defined as three consecutive CGM measures) in the range of \<54 mg/dl (\<3.0 mmol/l).
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Recurrent hypoglycemic event
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 frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Time at High Risk for Hypoglycemia
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
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Glycemia risk index
Defined by the formula \[3.0 × % time below 54mg/dl (3.0 mmol/l)\] +\[2.4 × % time below 70mg/dl (3.9 mmol/l)\] + \[1.6 × % time above 180mg/dl (10.0 mmol/l)\] + \[0.8 × % time above 250mg/dl (13.9 mmol/l)\].
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Prolonged hypoglycemic events level 1
A hypoglycaemic event 54 - 70 mg/dl (3.0 - 3.9 mmol/l) continuously for at least 120 minutes.
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Prolonged hypoglycemic event level 2
A hypoglycaemic event \<54 mg/dl (\<3.0 mmol/l) continuously for at least 120 minutes.
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Severe hypoglycemia
Patient requires assistance to correct hypoglycemia.
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Mean sensor glucose
Mean sensor glucose from the CGM in mg/dl (mmol/l).
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Standard deviation of the glucose distribution
The standard deviation mg/dl (mmol/l) from the CGM glucose measurements.
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Coefficient of variation
The standard deviation of the glucose distribution divided by the mean glucose level.
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
Length of stay
The amount of time spent in the hospital from admission untill discharge from the hospital
Time frame: From admission untill discharge from the hospital (up to 30 days)
In-hospital complications
Any in-hospital related complications occurring at least one day after randomization (e.g. acute kidney injury, sepsis, etc.)
Time frame: One day after randomisation until discharge from the hospital (up to 30 days)
Total daily insulin doses
The amoun of daily insulin given.
Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)
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