Why do we Need
an Artificial Pancreas?
Why do we Need an
Artificial Pancreas?
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Georgeanna J Klingensmith, MD
Barbara Davis Center
Keystone
2010
Georgeanna
J Klingensmith,
MD
Barbara Davis Center
Keystone 2010
Why do we need an
artificial pancreas?
• Current glycemic targets
• Current glycemic outcomes fall short
• What factors contribute to achieving
target glycemia
• Can current technology allow youth
to reach target glycemia?
ADA Glycemic Guidelines
Targets
Age
< 6yrs
6-12 yrs
13-18 yrs
adult
A1c % **
7.5-8.5
<8
<7.5
<7
** Goals should be individualized, a lower A1C goal is
reasonable based on benefit:risk assessment and if it can be
achieved without excessive hypoglycemia
Silverstein, et al. Care of Children with type 1 DM. Diabetes Care, 28:186212, 2005
ADA Standards of Care. Diabetes Care, Suppl 1, 2010
ISPAD Glycemic Guidelines for
all children and adolescents
A1C = <7.5% for all children
All targets should be individualized
Higher targets are recommended in those with severe
hypoglycemia and/or hypoglycemia unawareness
Rewers M, Pihoker C, Donaghue K, Hanas R, Swift P, Klingensmith
GJ. Assessment and Monitoring of Glycemic Control. ISPAD
clinical consensus guidelines 2009. Ped Diab 2009
Risk of Progression of Complications:
Related to Glycemia, the DCCT Study
Severe hypoglycemia
15
Diabetic retinopathy
Nephropathy
Neuropathy
Microalbuminuria
120
Rate of 100
Severe
Hypo. 80
(per
100 60
patient
-years) 40
13
11
Relative
Risk
9
7
5
3
20
0
GJ Klingensmith
1
6
7
8
9
10
HbA1c, %
11
12
DCCT Research Group. N Engl J Med. 1993;329:977-
The DCCT: A1C can be modified
and Technology Lowers A1C
1
DCCT
Intervention
DCCT
2
3
4
5
6
EDIC Observation
S t u d y Y e a r
7
8
9
Where are we in the
‘real world’ of pediatric diabetes?
The Hvidore Study Group on Childhood
Diabetes
A1C for participating centers
9.5
9.0
Mean
+/- SE
% A1c
8.5
Tosoh
method
8.0
7.5
Mean A1C 8.2 + 1.4%,
7.0
Diabetes Care, 30:2245-50, 9/2007
SEARCH for Diabetes A1c Results
6 clinical centers in US
Mean duration 5 years
Mean
8.33%
N=2999
8.24%
N=369
“Good”: age specific ADA A1c target
“Poor”: A1c ≥ 9.5%.
“Intermediate”: 1c between “good” and “poor”
Petitti D, et al, J Peds, Nov 2009
Factors associated with A1C
in Multifactorial Analysis
•
•
•
•
•
Age, DM duration
Insurance status
Household income
Parental education
Race/ ethnicity
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
When the HbA1c is adjusted for all of
these factors, mean A1C for T1D = 8.0%
Petitti D, et al, J Peds, Nov 2009
Insulin Regimen in SEARCH
Type 1, N=2743, duration >1 year
Insulin Regimen
Pump
A1C
Race
Asian/Pacific Isl.
Black
Hispanic
Native American
White
8.0 (1.1)
MDI:
Basal/Bolus
8.5 (1.6)
MDI:
Modified
B/B
8.9 (1.6)
MDI:
8.6 (1.6)
1-2
injections
8.6 (1.7) <.0001
Difference remains significant when
controlling for socio-economic
factors
Row %
6.1
5.3
12.3
0.0
26.3
38.9
13.8
17.2
27.8
26.4
6.1
5.3
8.0
11.1
11.2
20.4
29.3
28.6
31.3
46.3 <.0001
31.3
22.2
11.7
38.9
24.4
Journal of Pediatrics Aug 2009
Factors associated with
HbA1c in Multifactorial
Analysis
•
•
•
•
•
•
•
Age, DM duration
< 0.001
Insurance status
< 0.001
Household income
< 0.001
Parental education
< 0.001
Race/ ethnicity
< 0.001
Frequency of BG testing
< 0.001
Type of insulin/ insulin delivery <0.001
Improvement in HbA1c levels
%A1c
The Joslin Clinic
9.2
9.1
9.0
8.9
8.8
8.7
8.6
8.5
8.4
8.3
8.2
9.0
8.7
8.4
Baseline
8.7
Cohort 2 used more
intensive management with
more frequent SBGM and
Year 2
more on MDI and
CSII
Cohort 1 (1997-2000)
Cohort 2 (2002-2005)
A1c significantly lower for Cohort 2 compared to Cohort 1
at baseline (p=0.03) and two-year follow-up (p=0.04)
J Pediatr. 2007 Mar;150(3):279-85
Does the latest technology
help adolescents?
• JDRF sensor study
• Randomized controlled trial of
sensor use vs standard care
• 3 age groups
– >25
– 15-25
– 8-14
N Engl J Med. 2008. 359(14):1464-76
86%
30%
Only the >25 group had
an improvement in A1C
50%
Diabetes Care, 11/2009, 32 (11), p. 1952
Age Differences in Sensor
use at 6 months
% sensor
>6d/wk
>25 yrs
64%
15-25 yrs
19%*
8-14 yr
25%
*21% of 15-24 year olds were not wearing the sensor
at 6 months
Effectiveness of continuous glucose monitoring in a clinical
care environment: evidence from the JDRF-CGM trial
Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study
Group
Diabetes Care. 2010 Jan;33(1):17-22
Who successfully uses CGM
• Those >25 years (p<0.001)
• Those who test more frequently prior to
initiation of CGM (p<0.001)
• Those who wore the device >6 days a
week in the initial month (p<0.001)
• Those who achieved a greater percent
of glucose values of 70-180mg/dl in
month 1 (p<0.002)
Diabetes Care 2009;32: 1947-1953
Do we need an ‘artificial
pancreas’, or is CGM enough?
• Some pediatric patients can successfully
achieve A1C values <7% without
significant hypoglycemia for many years
• Even within a clinical trail, many cannot
achieve a significantly lower A1C with
CGM, due to the inability to consistently
wear the device
Why do we need an
‘artificial pancreas’?
 Current ‘usual’ therapy does not achieve
goal A1C values in over 50% of children
 Using more intensified management can
lower A1C levels in many patients
 The newest current technology - CGMcan also be important in achieving target
glycemic levels for some patients
Conclusion
• An artificial pancreas may remove
enough of the ‘human error’ and
‘hassle’ factor to allow more patients
to achieve success
• A cure for
adolescence
would also help