Why We Pump
Henry Anhalt, DO, CDE
Director, Pediatric Endocrinology and Diabetes
Saint Barnabas Medical Center
Livingston, NJ
Pump Gasoline?
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Pump Breast Milk?
THE PANCREAS THROUGHOUT
HISTORY
• 1550 BCE-Papyrus describes polyuria and its
treatment
• 4th century BCE-Ayur Veda of Susruta (India)
described sugarcream urine which attracted ants.
• 7th century CE-Chinese physician Chen Chuan
recorded sweet urine in diabetes
• 1869-Langerhans describes islets
• 1909-the name insuline is suggested by Jean de
Meyer (Brussels)
• 1921-Banting and Best-report discovering Insulin
used in 1922
BANTING-1891-1941 & BEST-1899-1978
Orthopod who
became a
physiologist and
died in air crash in
Newfoundland
while on wartime
mission
Together they isolated insulin
and Banting won the Nobel
Prize in 1923 knighted in
1934
First commercial insulin
Prevalence of Diabetes in the
US
Diagnosed
Type 2
Diabetes
14 million
1.5 million new cases of diabetes were
diagnosed in people aged 20 years or older
in 2005
Diagnosed
Type 1 Diabetes
1.5 Million(1:400600 children)
Undiagnosed
Diabetes
6 Million
Good Glycemic Control (Lower
HbA1c)
Reduces Incidence of Complications
DCCT
Kumamoto
UKPDS
9  7%
9  7%
8  7%
Retinopathy
63%
69%
17-21%
Nephropathy
54%
70%
24-33%
Neuropathy
60%
–
–
Macrovascular
disease
41%*
–
16%*
HbA1c
* not statistically significant
DCCT Research Group. N Engl J Med. 1993;329:977-986. Ohkubo Y et al. Diabetes Res Clin
Pract. 1995;28:103-117. UKPDS 33: Lancet. 1998;352:837-853.
HbA1c and Microvascular Complications
Retinopathy
15
13
Nephropathy
11
Relative 9
Risk 7
5
Neuropathy
3
1
7
8
9
10
HbA1c, %
11
12
10
Incidence of DiabetesRelated Complications (%)
Every 1% HbA1c Increase Above
Goal Elevates the Risk of Diabetic
Complications
50
40
+37%
30
+21%
20
+14%
+12%
10
0
Increase in Any
Diabetes-Related
Endpoint
Increase in Risk
of Myocardial
Infarction (MI)
Adapted from Stratton et al. BMJ. 2000;321:405-412.
Increase in Risk
of Stroke
Increase in Risk
of Microvascular
Complications
Physiology of Insulin and blood
glucose
Insulin
secretion
Basal Insulin
Breakfast
Lunch
Dinner
Blood
glucose
Basal blood glucose
Insulin Preparations
Onset of
Action
Duration of
Peak
Action
Humalog/Novalog 5 to 15 min
1 to 2 hr
4 to 6 hr
Human Regular
30 to 60 min
2 to 4 hr
6 to 10 hr
Human NPH
1 to 2 hr
4 to 6 hr
10 to 16 hr
Human Lente
1 to 2 hr
4 to 6 hr
10 to 16 hr
Human Ultralente
2 to 4 hr
Unpredictable
<24 hr
30minutes
none
24hr
Lantus
NPH and regular insulin - 2 injections
Bkfst
lunch
dinner
bedtime
bkfst
Disadvantages of NPH/ Regular
regimen
•
•
•
•
No flexibility:
Required certain amount of calories a day
Skipped meal - hypoglycemia (peak of NPH)
Exercise - hypoglycemia (excessive glucose
use)
• At night - hypoglycemia (peak of NPH)
• Overeating- hyperglycemia (not enough)
• Oversleeping- hyperglycemia (skipped dose)
Results of conventional
therapy
• Poor control - HbA1C 10% and higher
• Fear of hypoglycemia - worsening of
control
• Inability to exercise - poor fitness
• Early development of complications
• “OUT OF CONTROL”-Negative
reinforcement
• “Don’t Do This, Don’t Do That”
• Mauriac syndrome - chronic insulin
deficiency - stunted growth, hepatomegaly
Some causes of hypoglycemia in toddlers
and preschoolers:
– Unpredictable food intake and physical
activity.
– Imprecise administration of low doses of
insulin.
– Frequent viral infections.
– Inability to convey the symptoms of low blood
sugar.
Adapted from Litton J et al; J Pediatr 2002;141:490-495.
IN SEARCH OF
THE HOLY
GRAIL
Dr. Arnold Kadish of Los Angeles, California, devised the first insulin
pump in the early 1960s. It was worn on the back and was roughly
the size of a Marine backpack
Humalog/Novolog versus Regular
• Rapid acting insulins:
Start in 10min
Peak in 1-2h
Gone in 3.5-4h
• Regular insulin:
Starts in 30min
Peaks in 3-4h
Gone in 6-8h
Benefits of rapid acting insulins
• May be given just prior to the meal or after
meal in babies
• Time of action match rise in sugar caused
by most meals
• No action left at the time of next meal - no
boluses buildups
• Less activity at bedtime - less night “low’s”
and no need for bedtime snack
Insulin Effect
WHEN WE STARTED TO
DABBLE-THREE SHOTS A DAY
Lispro
Lispro
NPH
NPH
B
L
S
Meals
HS
B
Twice Daily vs. Three Daily
Injections
Rationale: Avoid Dawn Phenomenon
and Somogyi Effect
872 adolescents evaluated over a 3year period.
Either regimen:
– Increased insulin dose.
– Deterioration of metabolic control.
– Increase in BMI.
– Females faired worse than males.
Adapted from Holl R et al; Eur J Pediatr. 2003 Jan; 162(1): 22-9.
New Long Acting Insulin
(Glargine Insulin)
• Lantus is a
new type of
long acting
insulin that
has no peaks
• Mimics
physiological
insulin (basal)
INSULIN TACTICS
•
The Basal/Bolus Insulin
Basal Insulin Concept
– Insulin requirement to suppress hepatic glucose
production between meals
• Bolus Insulin (prandial)
– Insulin requirement to maintain normal glucose
disposal after eating
– Insulin:CHO Ratio = 500/(total starting dose)
– Correction Factor = 1500/(total starting dose)
– Correction factor in young children =
1800/(total starting dose)
Insulin Effect
LANTUS AND NOVOLOG-”POOR
MANS PUMP”
Lispro
Lispro
Lispro
lANTUS
B
L
S
Meals
HS
B
Nine Preschool Patients Meticulously
Cared For With MDI Switched To CSII:
Mean A1c 9.5% reduced
to 7.9%.
– Severe hypoglycemic
events 0.52 per month
reduced to 0.09 per month.
– Increased parental
confidence and
independence.
– All refused to relinquish
pump at completion of
study.
10
9
8
7
6
5
4
3
2
1
0
MDI
)%( HbA1c
Adapted from Litton J et al; J Pediatr 2002;141:490-495.
CSII
Severe hypoglycemic events
Better Control and Less
Hypoglycemia in Young Children
HbA1c
Litton J., J Pediatr 2002;141:490-495.
Hypoglycemia
Glycemic Memory: Sustained
Beneficial Effect Of Prior Intensive
Therapy
195 patients between the ages of 13 and
17 in DCCT:
– Decreased worsening of retinopathy by 74%
(p < 0.001).
– Decreased progression to proliferative or
severe
non-proliferative retinopathy by 78% (p <
0.007).
Adapted from White, N et al, J Pediatr. 2001 Dec; 139(6): 804-12.
Glycemic Memory: Sustained
Beneficial Effect Of Prior Intensive
Therapy
195 patients between the ages of 13 and 17 in
DCCT:
– Relative risk of hypoglycemia < 1 among prior
intensive group.
– Prevalence of microalbuminuria 48% less.
It is vital to achieve the best glycemic control
early in the course in diabetes during
adolescence and childhood.
Adapted from White, N et al, J Pediatr. 2001 Dec; 139(6): 804-12.
“ Less than optimal glycemic control during
the early years of diabetes has a lasting
detrimental effect on the development and
progression of complications, even after
better glycemic control is established later
in the course of the disease.”
Adapted from White, N et al, J Pediatr. 2001 Dec; 139(6): 804-12.
From Preschool to Prom
161 patients with type 1
diabetes:
– 26 ages 1 to 6
– 76 ages 7 to 11
– 59 ages 12 to 18
98% remained on CSII
Reduced hypoglycemia
(events/year)
– Age 1 to 6: 0.42 to
0.19
– Age 7 to 11: 0.33 to
0.22
– Age 12 to 18: 0.33 to
0.27
Pre
mos 21
9
8
7
6
5
4
3
2
1
0
< 7 years
Adapted from Ahern J et al; Pediatr Diabetes. 2002 Mar;3(1): 10-5.
7 to 11 years
Mean HbA1c levels
12 to 18 years
World youngest pumper in 1999: 5mo
old
World youngest pumper 2003: 10 d old
I WAS A NON-BELEIVER
• TOO HARD/TIME CONSUMING
• I WAS UNINFORMED ON HOW TO USE
THEM
• NOT FOR THE VERY YOUNG OR THE
UNMOTIVATED
• ONLY AFTER HONEYMOON
• YOU HAVE TO TEST FOR ME TO PUT
YOU ON PUMP
• YOU WILL SUFFER
PSYCHOLOGICALLY
Purpose and Method of Study
• Purpose: compare two algorithms of
management for newly diagnosed kids with
diabetes in our clinic.
• Method: A study of HbA1c level and total daily
insulin dose in 2 groups of patients with new
onset diabetes type 1 at diagnosis, 6 months,
and 12th months after diagnosis.
Hypothesis
•
Our hypothesis are:
1. Patients on pump have better control of their
blood glucose level
2. Better control allows extension of the “honey
moon” period
Treatment Algorithm
Algorithm #1
Algorithm #2
Treatment algorithm Group 1 (number of
patients = 24)
Treatment algorithm Group 2 (number of
patients = 11)
All patients with new onset diabetes were discharged
within 3-5 days.
All patients with new onset diabetes were discharged
within 24 hours.
Patients and parents were taught within 3 to 5 days inhospital how to manage diabetes by pediatric
endocrinology team.
Patients and parents were taught within first 24 hours inhospital how to manage diabetes by pediatric
endocrinology team.
Patients were started on Humalog and NPH in the hospital
after correction of diabetic ketoacidosis.
Patients were started on Humalog and Lantus after
correction of diabetic ketoacidosis and regiment was
continued for the first 1-2 weeks.
CSII was started within first 14 days after diagnosis.
A pediatric endocrinologist was available 24 hours a day 7
days a week to support insulin dose adjustment and
education over the phone for the patients and parents.
A pediatric endocrinologist was available 24 hours a day 7
days a week to support insulin dose adjustment and
education over the phone for the patients and parents.
HbA1c
HbA1C vs time
16.00
14.00
12.00
10.80
HbA1c
10.00
8.34
8.19
8.00
7.24
7.00
6.66
6.00
4.00
2.00
0.00
at dx
6mo
Time (months)
12mo
No pump
Pump
Total daily dose
Total daily dose
1.40
1.20
Insulin units/kg
1.00
0.82
0.80
0.72
No pump
Pump
0.62
0.60
0.51
0.45
0.46
0.40
0.20
0.00
at dx
at 6mo
Time (months)
at 12mo
Conclusion:
• Intensive teaching, 24 hour support, and CSII within 2
weeks of diagnosis improved patient’s HbA1c levels and
decreased total daily dosage of insulin over traditional
therapy.
• CSII was beneficial for newly diagnosed diabetes
patients at the onset of disease.
Candidates for pump therapy
Typical Criteria
My Criteria
• Any patient who is willing
• Only motivated patients
to start and has abilities
• only patients who showed
to learn
good compliance on
• May improve compliance
previous regimen
• Any age adults and
• Adults and children > 6y
children of any age
old
(independent users 7-80
y old)
• Particularly “noncompliant” patients
ADVERSE EVENTS
PSYCHOSOCIAL OUTCOMES
The Yale Experience
• > 200 children started on pumps over last 5 yrs
HbA1c
Age (yr)
pre
3 mos post
<7
7-12
7.6
7.8
6.7
7.3
13-18
7.9
7.5
• No difference in severe hypoglycemia
• Parents report less mild hypoglycemia
Ahern et al., Journal of Pediatric Endocrinology and
Metabolism 2000, 13(suppl 4):1220.
Additional Evidence From Yale
8.5
8
•Decreased hypoglycemia
7.5
•No change in BMI or TDD
•98% remained on CSII
Pre
12 mos
Recent
7
HbA1c
6.5
6
5.5
< 7 years
7-11 years
12-18 years
Ahern, JAH, et.al. Pediatric Diabetes 2002;3:10-15.
CSII vs. MDI With Glargine
in Children
Randomized, Parallel-group, 16 week study
Subjects at baseline
Age: 8-19 yr (mean 12.7 ± 2.7)
Type 1 DM > 1 yr duration
Standard insulin therapy (2-3 injections/day)
CSII (aspart) n=12
Injection
therapy
MDI (aspart/glargine) n=14
Boland et al., Diabetes 2003, 52:S1, A45, 192-OR
Pump Group Achieved Better
Control Overall
Changes in HbA1c Levels
8.5
p=.30
8
p=.15 (NS)
(NS)
p = .03
7.5
Pump
MDI
7
6.5
Baseline
4 wks
8 wks
12 wks
Boland, E. Diabetes 52,(Suppl 1), 2003 Abstract 192.
16 wks
More Pump Wearers Achieved
HbA1c _< 6.9%
% Patients Achieving
HbA1c < 6.9%
50
40
30
20
10
0
Pump
Glargine
Boland, E. Diabetes 52,(Suppl 1), 2003 Abstract 192.
Sweden’s Experience
•
•
•
•
89 children 3-21 y.o
Diabetes duration 6.1 years
30% using CSII
HbA1c decreased from 9.2% to 8.4% after
CSII start
• Severe hypos
–Pump: 11.1/100 pt years
–MDI: 40.3/100 pt years
. Hanas, Diabetes, 2000, 49 (Suppl 1):A133.
Patient Characteristics of
Successful Pediatric
Pumpers
• Able to maintain follow up appointments
with health care provider
• Willing to record blood glucose values
• Able to count carbohydrates
• Good family/social support system
Pump therapy benefits
• Improved control - more physiological basal
rates (“dawn phenomenon” match), different
boluses for food, less absorption variability
• Less hypoglycemia
• More flexible lifestyle and possibility to exercise
• Precise dosing - 0.1u - 0.025u increments for
basal rate and boluses
• Less injections - improved quality of life
• Less possibility of overdose
Adapted from Plotnick L et al; Diabetes Care 2003; 26(4):1142-1146.
Pump Use in Children Is
Increasing
• 200,000 users (adults and kids in the US). 10,000 are adults with
type 2 diabetes
• ~ 20,000 children using pump therapy
– 10% of all children with diabetes
•
•
•
•
Penetration as high as 90% in some pediatric clinics (ours)
Increasing use in younger children (as young as 10 months)
Current outcomes indicate CSII is safe and effective in children
Increasing acceptance likely due to DCCT findings as well as the
introduction of smaller, safer insulin pumps
• There are approximately 400,000 insulin pump users worldwide
Avoiding DKA
• Give a pen with the pump
• Instruct that any time the patient feels
nauseated or has abdominal pain -- change
the site
• Blood sugar is greater than 250 mg/dl
– Take correction dose
– Check for ketones
– Recheck in 60 minutes
• If coming down, leave alone
• If not, take a shot and change the site
Summary
• Pump therapy is an intensive process for
pediatric patients and their families and the
diabetes education team.
• Successful pumpers are motivated and willing to
maintain follow-up, carbohydrate count, and
check blood glucose frequently.
• Benefits of pump therapy for pediatric patients
include: improved lifestyle, decrease in
hypoglycemia, accurate dosing , ability to review
history to see if doses were actually given.
Summary
• Children with diabetes should be intensively
treated to avoid short and long term
complications
• Insulin pumps can provide better control and
less hypoglycemia than MDI
• With good support and a standardized
process, insulin pump therapy can help to
improve diabetes management in children
• Insulin pump therapy should be the only form
of therapy offered to children with diabetes
When meditating over a
disease, I never think of finding
a remedy for it, but rather, a
means of preventing it.
Louis Pasteur, 1884