In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can ...improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care.
In this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital discharge.
The mean (±SD) percentage of time that the sensor glucose measurement was in the target range was 65.8±16.8% in the closed-loop group and 41.5±16.9% in the control group, a difference of 24.3±2.9 percentage points (95% confidence interval CI, 18.6 to 30.0; P<0.001); values above the target range were found in 23.6±16.6% and 49.5±22.8% of the patients, respectively, a difference of 25.9±3.4 percentage points (95% CI, 19.2 to 32.7; P<0.001). The mean glucose level was 154 mg per deciliter (8.5 mmol per liter) in the closed-loop group and 188 mg per deciliter (10.4 mmol per liter) in the control group (P<0.001). There was no significant between-group difference in the duration of hypoglycemia (as defined by a sensor glucose measurement of <54 mg per deciliter; P=0.80) or in the amount of insulin that was delivered (median dose, 44.4 U and 40.2 U, respectively; P=0.50). No episode of severe hypoglycemia or clinically significant hyperglycemia with ketonemia occurred in either trial group.
Among inpatients with type 2 diabetes receiving noncritical care, the use of an automated, closed-loop insulin-delivery system resulted in significantly better glycemic control than conventional subcutaneous insulin therapy, without a higher risk of hypoglycemia. (Funded by Diabetes UK and others; ClinicalTrials.gov number, NCT01774565 .).
Automated fully closed-loop (CL) insulin delivery system without meal-bolusing was evaluated in medical and surgical non-critical care wards of two acute hospitals in Switzerland and United Kingdom. ...In a randomised controlled parallel design study, 136 adults with inpatient hyperglycaemia requiring subcutaneous (s/c) insulin were randomised to receive either CL-directed s/c insulin delivery (n=70) or conventional s/c insulin therapy as per local practice with masked continuous glucose monitoring (n=66) for up to 15-days. Participants consumed self-selected hospital meals and were matched for age (68±10 vs. 67±13 years; CL vs. control), HbA1c (7.8±2.5 vs. 8.0±1.9%) and BMI (32.7±8.2 vs. 32.3±8.1kg/m2). During CL, participant’s usual insulin and sulphonylurea therapy were withheld. In an intention to treat analysis, the proportion of time when sensor glucose was in target range from 5.6 to 10.0mmol/l was significantly higher during CL (p<0.001, Table). CL reduced time spent above target (p<0.001), and reduced mean and standard deviation of sensor glucose (p<0.001). Time spent hypoglycaemic was low and comparable. Total daily insulin delivery was not different. No severe hypoglycaemia or serious adverse events occurred in either group.
In conclusion, fully closed-loop without meal-bolusing is safe, and may improve glucose control in a heterogeneous inpatient population.Closed-loop insulin delivery (n=70)Conventional insulin therapy (n=66)PTime spent at sensor glucose levels (%)5.6 to 10.0 mmol/l65.7±16.841.5±16.9<0.001>10.0 mmol/l23.7±16.649.5±22.8<0.001<5.6 mmol/l10.6±6.79.0±13.30.37<3.0 mmol/l0.0 (0.0, 0.1)0.0 (0.0, 0.0)0.80Mean sensor glucose (mmol/l)8.5±1.610.5±2.4<0.001SD of sensor glucose (mmol/l)2.6±1.03.2±1.1<0.001Total daily insulin (U)44.0 (27.5, 73.3)40.2 (26.5, 65.6)0.36Data are mean ± SD or median (IQR).
Disclosure
L. Bally: None. H. Thabit: None. S. Hartnell: Speaker’s Bureau; Self; Medtronic, Roche Pharma. E. Andereggen: None. Y. Ruan: None. M.E. Wilinska: None. M. Evans: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, Cellnovo, Roche Pharma. Speaker’s Bureau; Self; Abbott, Novo Nordisk A/S. M.M. Wertli: None. A.P. Coll: None. C. Stettler: None. R. Hovorka: Speaker’s Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company, AstraZeneca. Other Relationship; Self; B. Braun Medical Inc.. Research Support; Self; Medtronic. Other Relationship; Self; Medtronic. Research Support; Self; Abbott, JDRF, Diabetes UK, National Institute of Diabetes and Digestive and Kidney Diseases.
Aim: To assess the ability of fully closed-loop insulin delivery to accommodate day-to-day variability in insulin requirements in noncritical care setting.
Methods: We retrospectively analyzed ...insulin delivery during closed-loop studies in inpatients with hyperglycaemia requiring insulin on general wards (type 1 diabetes excluded). Coefficient of variation (CV) quantified day-to-day variability of insulin requirements over 5 to 15 days of closed-loop use. Participants were stratified into tertiles according to variability of insulin requirements.
Results: Data from 487 days (55 participants) were analyzed. Participants with higher CV of insulin requirements had comparable mean glucose (149 vs. 153mg/dL; P=0.59; Table) and time in target glucose 100-180mg/dL (67.8 vs. 67.9%; P=0.99) to those with lower CV. There was no increase in hypoglycemia in those with higher CV (P=0.67). Those with higher CV were younger than those with lower CV (66 vs. 72years; P=0.037). Weight, gender, HbA1c, diabetes/insulin duration, use of steroids/dialysis/nutrition support were comparable (ns).
Conclusions: Fully closed-loop insulin delivery can accommodate highly variable insulin requirements without compromising glucose control or increasing the risk of hypoglycaemia in inpatients receiving insulin therapy on general wards.
Disclosure
C.K. Boughton: None. L. Bally: None. H. Thabit: Research Support; Self; Dexcom, Inc. S. Hartnell: Advisory Panel; Self; Dexcom, Inc., JDRF. Speaker's Bureau; Self; Sanofi. D. Herzig: None. A. Vogt: None. E. Andereggen: None. Y. Ruan: None. M.E. Wilinska: None. M. Evans: Advisory Panel; Self; Dexcom, Inc., Medtronic, Roche Diabetes Care, Zucara Therapeutics Inc. Research Support; Self; MedImmune, Sanofi. Speaker's Bureau; Self; AstraZeneca. Other Relationship; Self; Abbott, Eli Lilly and Company, Novo Nordisk Inc. M.M. Wertli: None. A.P. Coll: None. C. Stettler: None. R. Hovorka: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; Abbott, Dexcom, Inc., Medtronic. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; B. Braun Medical Inc., Medtronic.
Aim: To characterize variability of exogenous insulin requirements during fully closed-loop insulin delivery in hospitalized patients with hyperglycaemia requiring subcutaneous insulin.
Methods: We ...retrospectively analyzed data from randomized trials investigating fully closed-loop insulin delivery for up to 15 days in inpatients with hyperglycaemia on general wards (type 1 diabetes excluded). We calculated insulin amounts delivered by closed-loop overnight (2300-0449), during breakfast (0500-1059), lunch (1100-1659), and evening meal (1700-2249). The coefficient of variation (CV) quantified between day and between night variability of insulin requirements in inpatients using closed-loop for at least 5 days.
Results: Data from 487 days in 55 participants were analyzed age 69(8)years, weight 100(32)kg, baseline HbA1c 8.0(2.1)%, duration of diabetes 18(13)years, duration of insulin 9(10)years, mean(SD); 14.5% of participants received dialysis, 29.1% enteral/parenteral nutrition and 21.8% steroids. Closed-loop directed insulin infusion rate was 1.6(0.8), 2.9(1.2), 3.1(1.4), 2.1(1.0)units/kg/h during overnight, breakfast, lunch, and evening meal periods, respectively. The CV of insulin delivery was higher between nights than between any of the daytime periods overnight 54(21)% compared with 42(21)% at breakfast, 41(16)% lunchtime and 48(17)% dinner; p=0.001.
Conclusions: Overnight exogenous insulin requirements are more variable than daytime requirements. Particular attention needs to be paid to glucose management overnight to prevent dysglycaemia in inpatients receiving insulin therapy on general wards.
Disclosure
C.K. Boughton: None. L. Bally: None. H. Thabit: Research Support; Self; Dexcom, Inc. S. Hartnell: Advisory Panel; Self; Dexcom, Inc., JDRF. Speaker's Bureau; Self; Sanofi. D. Herzig: None. A. Vogt: None. E. Andereggen: None. Y. Ruan: None. M.E. Wilinska: None. M. Evans: Advisory Panel; Self; Dexcom, Inc., Medtronic, Roche Diabetes Care, Zucara Therapeutics Inc. Research Support; Self; MedImmune, Sanofi. Speaker's Bureau; Self; AstraZeneca. Other Relationship; Self; Abbott, Eli Lilly and Company, Novo Nordisk Inc. M.M. Wertli: None. A.P. Coll: None. C. Stettler: None. R. Hovorka: Advisory Panel; Self; Novo Nordisk A/S. Research Support; Self; Abbott, Dexcom, Inc., Medtronic. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; B. Braun Medical Inc., Medtronic.
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