Evaluation of an Algorithm to Guide Patients With Type 1 Diabetes Treated With Continuous Subcutaneous Insulin Infusion on How to Respond to Real-Time Continuous Glucose Levels: A randomized controlled trial
ALICIA J. JENKINS
BALASUBRAMANIUM KRISHNAMURTHY
JAMES D. BEST
FERGUS J. CAMERON
PETER G. COLMAN
STEVEN FARISH
MED
PETER S. HAMBLIN
FRACP
MICHELE A. O'CONNELL
MRCPI
CHRISTINE RODDA
PHD
KEVIN ROWLEY
PHD
HELENA TEEDE
PHD
DAVID N. O'NEAL
OBJECTIVE - To evaluate an algorithm guiding responses of continuous subcutaneous insulin infusion (CSII)-treated type 1 diabetic patients using real-time continuous glucose monitoring (RT-CGM). RESEARCH DESIGN AND METHODS - Sixty CSII-treated type 1 diabetic participants (aged 13-70 years, including adult and adolescent subgroups, with A1C 9.5%) were randomized in age-, sex-, and A1C-matched pairs. Phase 1 was an open 16-week multicenter randomized controlled trial. Group A was treated with CSII/RT-CGM with the algorithm, and group B was treated with CSII/RT-CGM without the algorithm. The primary outcome was the difference in time in target (4 -10 mmol/l) glucose range on 6-day masked CGM. Secondary outcomes were differences in A1C, low (3.9 mmol/l) glucose CGM time, and glycemic variability. Phase 2 was the week 16 -32 follow-up. Group A was returned to usual care, and group B was provided with the algorithm. Glycemia parameters were as above. Comparisons were made between baseline and 16 weeks and 32 weeks. RESULTS - In phase 1, after withdrawals 29 of 30 subjects were left in group A and 28 of 30 subjects were left in group B. The change in target glucose time did not differ between groups. A1C fell (mean 7.9% [95% CI 7.7- 8.2to 7.6% [7.2- 8.0]; P 0.03) in group A but not in group B (7.8% [7.5- 8.1] to 7.7 [7.3- 8.0]; NS) with no difference between groups. More subjects in group A achieved A1C 7% than those in group B (2 of 29 to 14 of 29 vs. 4 of 28 to 7 of 28; P 0.015). In phase 2, one participant was lost from each group. In group A, A1C returned to baseline with RT-CGM discontinuation but did not change in group B, who continued RT-CGM with addition of the algorithm.
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CONCLUSIONS Early but not late
algorithm provision to type 1 diabetic patients
using CSII/RT-CGM did not increase the target
glucose time but increased achievement of
A1C 7%. Upon RT-CGM cessation, A1C
returned to baseline.
R toring (RT-CGM) can be integrated
eal time-continuous glucose
moniwith a continuous subcutaneous
insulin infusion (CSII) device (1,2).
Interstitial glucose readings, with direction
and rate of change, are displayed and
linked to low and high glucose alarms.
Data can be uploaded and reviewed
retrospectively. Apart from recent devices
with automatic shutoff for low glucose,
RT-CGM cannot initiate insulin delivery.
Insulin changes must be initiated by the
patient or caregiver. Continuous glucose
monitoring (CGM) data interpretation
can be difficult, and advice guiding
insulin or lifestyle change may enhance
benefits (3).
In this study, we tested the glycemia
effects of an algorithm guiding responses
to RT-CGM in CSII-using type 1 diabetic
subjects. We also evaluated whether
glucose changes persisted after RT-CGM
withdrawal and whether late algorithm
introduction improved glycemia.
RESEARCH DESIGN AND
METHODS The study was an ethics
committeeapproved randomized
controlled trial at three adult and two
pediatric Australian centers. Written informed
consent was obtained, including guardian
consent for pediatric participants.
Participants were recruited in pairs
matched for age (within 5 years), sex, and
A1C (within 1%). Inclusion criteria were
age 13 years, type 1 diabetes duration
1 year, 3 months CSII with bolus
calculator use, A1C 9.5%, self-monitoring
of blood glucose 4 times daily, Internet
access, and willingness to use RT-CGM
for 6 of each 7 days for the study duration.
Exclusion criteria were physical or
intellectual limitations, renal impairment
(estimated glomerular filtration rate 60 ml/
min), using or likely to require steroid
therapy, gastroparesis, untreated celiac or
thyroid disease, hemoglobinopathies,
regular blood transfusions, current or
planned pregnancy, and breast-feeding.
No data were available regarding
glycemia after RT-CGM initiation at time of
study design. The only CGM data
available were retrospective continuous
glucose monitoring system (Medtronic,
Northridge, CA) traces recorded within 3
months after CSII commencement
(without RT-CGM) in 40 patients at one adult
center, which demonstrated a 33%
increase in 4 10 mmol/l time to 58% (17%)
and mean SD A1C reduction from
7.9 1.4 to 7.1 1.0%. A
betweengroup difference in the target glycemia
time increment of 25% was chosen for the
study because the impact of RT-CGM and
the algorithm was expected to be less than
that of CSII initiation. Thirty participants
in each (algorithm and nonalgorithm)
group had 99% power to detect a 25%
difference between groups at the 0.05
significance level. Corresponding power for
18 adults and 12 adolescents per group
was 95 and 90%, respectively.
Protocol
A history was obtained, physical
examination was performed, and blood an (...truncated)