Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a multicenter 2 × 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS).
OBJECTIVE
To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG).


METHODS
A 24-week 2 × 2 factorial randomized controlled trial in adults with type 1 diabetes and IAH was conducted. All received comparable education, support, and congruent therapeutic targets aimed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control. Primary end point was between-intervention difference in 24-week hypoglycemia awareness (Gold score).


RESULTS
A total of 96 participants (mean diabetes duration 29 years) were randomized. Overall, biochemical hypoglycemia (≤3.0 mmol/L) decreased (53 ± 63 to 24 ± 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA1c. Hypoglycemia awareness improved (5.1 ± 1.1 to 4.1 ± 1.6; P = 0.0001 [t test]) with decreased SH (8.9 ± 13.4 to 0.8 ± 1.8 episodes/patient-year; P = 0.0001 [t test]). At 24 weeks, there was no significant difference in awareness comparing CSII with MDI (4.1 ± 1.6 vs. 4.2 ± 1.7; difference 0.1; 95% CI -0.6 to 0.8) and RT with SMBG (4.3 ± 1.6 vs. 4.0 ± 1.7; difference -0.3; 95% CI -1.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH, fear of hypoglycemia, and insulin doses with equivalent HbA1c. Treatment satisfaction was higher with CSII than MDI (32 ± 3 vs. 29 ± 6; P = 0.0003 [t test]), but comparable with SMBG and RT (30 ± 5 vs. 30 ± 5; P = 0.79 [t test]).


CONCLUSIONS
Hypoglycemia awareness can be improved and recurrent SH prevented in long-standing type 1 diabetes without relaxing HbA1c. Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT, although satisfaction was higher with CSII.
Institute of Cellular Medicine, Newcastle University, Newcastle, U.K.
Stuart A
SA
Little
Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge, Cambridge, U.K.
Lalantha
L
Leelarathna
School of Medicine and Biomedical Sciences, Sheffield University, U.K.
Emma
E
Walkinshaw
Peninsula College of Medicine and Dentistry, Plymouth, U.K.
Horng Kai
HK
Tan
Bournemouth Diabetes and Endocrine Centre, Royal Bournemouth Hospital, Bournemouth, U.K.
Olivia
O
Chapple
School of Medicine and Biomedical Sciences, Sheffield University, U.K.
Alexandra
A
Lubina-Solomon
Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University, Newcastle, U.K.
Thomas J
TJ
Chadwick
AHP Research, Hornchurch, U.K.
Shalleen
S
Barendse
Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University, Newcastle, U.K.
Deborah D
DD
Stocken
Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University, Newcastle, U.K.
Catherine
C
Brennand
Institute of Cellular Medicine, Newcastle University, Newcastle, U.K.
Sally M
SM
Marshall
Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University, Newcastle, U.K.
Ruth
R
Wood
AHP Research, Hornchurch, U.K.The Australian Centre for Behavioural Research in Diabetes, Diabetes Australia-Vic, Melbourne, AustraliaCentre for Mental Health and Wellbeing Research, School of Psychology, Deakin University, Burwood, Australia.
Jane
J
Speight
Centre for Postgraduate Medical Research and Education, Bournemouth University, U.K.
David
D
Kerr
Peninsula College of Medicine and Dentistry, Plymouth, U.K.
Daniel
D
Flanagan
School of Medicine and Biomedical Sciences, Sheffield University, U.K.
Simon R
SR
Heller
Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge, Cambridge, U.K.
Mark L
ML
Evans
Institute of Cellular Medicine, Newcastle University, Newcastle, U.K.
James A M
JA
Shaw
D000293:Adolescent; D000328:Adult; D000368:Aged; D001364:Awareness; D001786:Blood Glucose / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control / Q000523:psychology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D055104:Infusions, Subcutaneous; D007267:Injections; D007328:Insulin / Q000008:administration & dosage*; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D012008:Recurrence; D055815:Young Adult
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin