Transcript Slide 1

Stopping Basal Insulin during Exercise
Markedly Reduces the Risk of
Hypoglycemia in Children with Type 1
Diabetes on Insulin Pump Therapy
Supported by NIH/NICHD Grants
HD041919,HD041915,HD041890,HD041918,HD041908, HD041906; GCRC Grants
RR00069,RR00059,RR06022,RR00070
Michael Tansey,1 Eva Tsalikian,1 Roy W. Beck,2 Rosanna Fiallo-Scharer,3
Kathleen Janz,1 Larry Fox,4 Darrell Wilson,5 Stuart Weinzimer,6 William
Tamborlane,6 Michael Steffes,7 Dongyuan Xing,2 Katrina Ruedy2 and the
Diabetes Research in Children Network (DirecNet) Study Group. 1Iowa
City, IA; 2Tampa, FL; 3Denver, CO; 4Jacksonville, FL; 5Stanford, CA;
6New Haven, CT; 7Minneapolis, MN
Abstract
Aerobic exercise is an important component of T1D management, but fear of hypoglycemia often deters children from
getting the recommended amounts of exercise. Strategies for preventing hypoglycemia during exercise in children with T1D
have not been well studied.
To evaluate the effect of basal insulin on exercise induced hypoglycemia, DirecNet conducted a study of 49 children 8-17y
with T1D on insulin pumps. Frequently sampled blood glucose (BG) concentrations (measured in the DirecNet Central
Laboratory) were compared during exercise with and without basal insulin using a randomized, crossover design. Baseline
BG concentrations were managed to remain within a target range of 120-200mg/dL. Each exercise session, performed from
~4-5 p.m., consisted of four 15min treadmill cycles at a target heart rate of 140 bpm interspersed with three 5min rest
breaks over 75min.
Hypoglycemia (≤70mg/dL) during exercise was significantly reduced when the basal insulin was discontinued.
Hypoglycemia occurred only on the basal-continued visit in 15 subjects (31%), only on the basal-stopped visit in 2 (4%), on
both visits in 6 (12%), and on neither visit in 26 (53%).
Basal-Continued
(N=49)
Basal-Stopped
(N=49)
P-value
mean ± SD or # (%)
Baseline BG
156 ± 27
161 ± 24
0.30
Hypoglycemia
21 (43%)
8 (16%)
0.003
63 ± 33
44 ± 38
<0.001
41% ± 19%
28% ± 23%
<0.001
BG Fall
% BG Fall
Hyperglycemia (BG >200mg/dL) was present at the end of exercise in 1 subject (2%) on the basal-continued visit and in 6
(12%) on the basal-stopped visit (p=0.12).
Discontinuing basal insulin during exercise is an effective strategy for reducing hypoglycemia in children with T1D, but the risk
of hyperglycemia may be increased.
Background
• There are many benefits of exercise in
patients with type 1 diabetes (T1DM)
• Many children with T1DM participate in
organized physical activity
• Exercise is associated with an increased
risk of hypoglycemia in patients with
diabetes who take insulin
• Patients using insulin pumps can alter
their basal rates around periods of activity
Study Aims
• Primary aim:
– To determine the effects of continuing or
discontinuing the basal rate upon the risk of
hypoglycemia around structured exercise
• Secondary aims:
– Determine the effect of basal rate on or off
upon the risk for hyperglycemia
Study Protocol
• 2 CRC admissions (~7 hour stays) 1-4 weeks apart,
crossover design
• Conditions:
– Both admissions with exercise sessions between 4-6PM
– Same lunch meals and bolus insulin doses for both admissions
– Basal insulin on (basal-continued) or off (basal-stopped)
during exercise
– Baseline BG concentrations were managed to remain within a
target range of 120-200 mg/dL prior to exercise.
– Pump was turned off at the beginning of one of the exercise
sessions and re-started 45 minutes post-exercise (off for
approximately 2 hours)
– Glucose measurements every 20 minutes during exercise and
every 15 minutes for 45 minutes following exercise
Study Protocol
• If during exercise the blood glucose dropped to
≤65 mg/dL, the subject was given 15-30g of
carbohydrate and rechecked after 5 to 15
minutes
• Exercise did not resume until the blood glucose
was >70 mg/dL
• Prior to starting and at the completion of the
exercise session, urine ketones were checked
and blood ketones were checked by fingerstick
using a Precision XtraTM meter
Exercise Protocol
Five minute rest periods
Treadmill
Exercise
0
Exercise
15
20
Exercise
35
40
55
TIME (minutes)
Exercise
60
75
90 105 120
ON or OFF basal insulin
Exercise at ~55% maximum effort (VO2max):
Target heart rate of 140 beats/minute
Patient Demographics
Subjects
N=49
Mean Age
14.5 ± 2.1 (yrs)
Mean Duration of T1D
7.2 ± 3.8 (yrs)
Mean HbA1c
7.5 ± 0.9%.
Gender
43% female
Results
• Baseline plasma glucose concentrations prior to the start
of the exercise measured at the central laboratory
ranged from 115 to 230 mg/dL (all but one of the
Freestyle values were within the specified range of 120
to 200 mg/dL).
• Baseline values were similar on basal-continued and
basal-stopped visits (mean ± SD = 156 ± 27 vs. 161 ± 24
mg/dL; P=0.30).
• Blood and urine ketone levels remained suppressed
during and after exercise
• None of the subjects during the basal-stopped study
required more than one carbohydrate snack vs. one-third
of the subjects during the basal-continued study
Treatment for Hypoglycemia
25
20
Number of 15
Subjects
10
Basal Stopped
Basal Continued
5
0
1x
2x
3x
4x
Number of times treated for
hypoglycemia during or
following exercise
Reductions in Glucose and hypoglycemia during/following
Exercise
BasalBasalP(mg/dL; N (%)
or mean ± SD)
Continued
(N=49)
Stopped
(N=49)
value
156 ± 27
161 ± 24
0.30
63 ± 33
44 ± 38
<0.001
% Glucose Dropb
41% ± 19%
28% ± 23%
<0.001
Hypoglycemiac,d
21 (43%)
8 (16%)
0.003
Hyperglycemiae
2 (4%)
6 (12%)
0.11
Hypoglycemiac
4
0
Hyperglycemiae
1
7
Baseline
During Exercise
(0-75 min)
Glucose Dropa
Additional Events
Following Exercise
a – Baseline glucose minus nadir
b – Glucose Drop divided by baseline glucose (expressed as a percentage)
c – Glucose ≤70 mg/dL
d – Includes 2 visits (1 basal-stopped and 1 basal-continued) where treatment was given for hypoglycemia
based on a meter glucose value, but the central laboratory value was >70 mg/dL (85 and 71 mg/dL) P=0.001
for analysis restricted to laboratory confirmed cases
e –Glucose ≥200 mg/dL and ≥20% increase from baseline
150
100
50
Basal Continued
Basal Stopped
0
Glucose
during Exercise
Exercise (mg/dL)
(mg/dL)
during
Glucose
200
Figure 1. Median Glucose Concentrations during/following
Exercise (N=98 visits from 49 subjects)
Baseline
Rest #1
Rest #2
Rest #3
End
Post 15
Post 30
Post 45
Black dots denote mean values and boxes denote median, 25th and 75th percentiles.
Figure 2A. Glucose Concentrations at Baseline Level vs
Nadir Glucose During Exercise (N=98 visits from 49 subjects)
280
Nadir Glucose during Exercise
260
240
Basal Continued
Basal Stopped
220
200
180
160
140
120
100
80
60
40
100
120
140
160
180
200
Glucose Value at Baseline (mg/dL)
220
240
The nadir glucose concentration during exercise (A) and glucose concentration
45 minutes after completion of exercise (B) are shown by baseline level. Dashed
lines denote the hypo- and hyperglycemia thresholds of 70 and 200 mg/dL,
respectively. Note different scales on the horizontal and vertical axes.
Figure 2B. Glucose Concentrations by Baseline Level vs 45
minute Post-Exercise (N=98 visits from 49 subjects)
280
Glucose 45 min Post-Exercise
260
Basal Continued
Basal Stopped
240
220
200
180
160
140
120
100
80
60
40
100
120
140
160
180
200
Glucose Value at Baseline (mg/dL)
220
240
The nadir glucose concentration during exercise (A) and glucose concentration
45 minutes after completion of exercise (B) are shown by baseline level. Dashed
lines denote the hypo- and hyperglycemia thresholds of 70 and 200 mg/dL,
respectively. Note different scales on the horizontal and vertical axes.
Conclusions
• The risk of hypoglycemia occurring during the
exercise period is reduced by stopping the basal
insulin infusion at the start of exercise.
However, this did not completely eliminate the
risk of hypoglycemia in the basal-stopped group.
– Treatment for hypoglycemia was rarely required if the
pre-exercise plasma glucose level was >130 mg/dL
– The response to treatment of hypoglycemia was more
effective under basal-stopped conditions
Conclusions (cont’d)
• Stopping the basal insulin infusion just prior to
starting a prolonged period of moderate aerobic
exercise is a safe and effective means of
markedly reducing the risk of hypoglycemia,
especially if pre-exercise glucose levels are
>130 mg/dl.
• The risk of becoming hyperglycemic may
increase when suspension of the basal insulin
infusion rate extends beyond 75 minutes.
Therapeutic Implications
• Check glucose pre-exercise and:
– Take 15-30 gms of CHO if glucose is <130 mg/dl
– Take small correction dose if glucose is >200 mg/dl
• Suspend or disconnect pump during exercise
• Recheck glucose after 60-90 min and reconnect
or give bolus if glucose levels have increased
above pre-exercise values
•
Barbara Davis Center
– H. Peter Chase
– Rosanna Fiallo-Scharer
– Laurel Messer
– Barbara Tallant
•
University of Iowa
– Eva Tsalikian
– Michael Tansey
– Kathleen Janz
– Linda Larson
– Julie Coffey
– Joanne Cabbage
•
Nemours Children’s Clinic
– Tim Wysocki
– Nelly Mauras
– Larry Fox
– Keisha Bird
– Kim Englert
•
Stanford University
– Bruce Buckingham
– Darrell Wilson
– Jennifer Block
– Paula Clinton
•
Yale University
– William Tamborlane
– Stuart Weinzimer
– Elizabeth Doyle
– Kristen Sikes
– Amy Steffen
•
Jaeb Center for Health Research
– Roy Beck
– Katrina Ruedy
– Craig Kollman
– Dongyuan Xing
– Cynthia Stocldale
Jaeb Center for Health Research