Why We Pump

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Why We Pump
Henry Anhalt, DO, CDE Director, Pediatric
Endocrinology and Diabetes Saint Barnabas Medical
Center Livingston, NJ
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• In the past we had a light that flickered, in
  the present, a light that flames, and in the
  future we will have a light that shines over all
  the land and the sea
• Winston Churchill

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Pump Gasoline?
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Pump Iron?
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Pump Breast Milk?
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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
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First commercial insulin
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Prevalence of Diabetes in the US
Diagnosed Type 1 Diabetes1.5
Million(1400-600 children)
Diagnosed Type 2 Diabetes14 million
Undiagnosed Diabetes6 Million
1.5 million new cases of diabetes were diagnosed
in people aged 20 years or older in 2005

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Good Glycemic Control (Lower HbA1c) Reduces
Incidence of Complications
DCCT 9 ? 7 63 54 60 41
Kumamoto 9 ? 7 69 70
UKPDS 8 ? 7 17-21 24-33 16
HbA1c Retinopathy Nephropathy Neuropathy Macrova
scular disease
not statistically significant
DCCT Research Group. N Engl J Med.
1993329977-986. Ohkubo Y et al. Diabetes Res
Clin Pract. 199528103-117. UKPDS 33 Lancet.
1998352837-853.
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HbA1c and Microvascular Complications
Retinopathy
15 13 11 9 7 5 3 1
Nephropathy
Relative Risk
Neuropathy
7
8
9
10
11
12
HbA1c,
10
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Every 1 HbA1c Increase Above Goal Elevates the
Risk of Diabetic Complications
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Incidence of Diabetes-Related Complications ()
21
14
12
Increase in Any Diabetes-Related Endpoint
Increase in Risk of Myocardial Infarction (MI)
Increase in Risk of Stroke
Increase in Risk of Microvascular Complications
Adapted from Stratton et al. BMJ.
2000321405-412.
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Physiology of Insulin and blood glucose
Insulin secretion
Basal Insulin
Breakfast Lunch Dinner
Blood glucose
Basal blood glucose
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Insulin Preparations
Onset of Duration of Action 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 lt24
hr Lantus 30minutes none 24hr
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NPH and regular insulin - 2 injections
Bkfst lunch dinner
bedtime bkfst
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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)

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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
• Dont Do This, Dont Do That
• Mauriac syndrome - chronic insulin deficiency -
  stunted growth, hepatomegaly

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• 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
2002141490-495.
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• IN SEARCH OF THE HOLY GRAIL

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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
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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

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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 lows and
  no need for bedtime snack

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New Long Acting Insulin (Glargine Insulin)

• Lantus is a new type of long acting insulin that
  has no peaks
• Mimics physiological insulin (basal)

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INSULIN TACTICS The Basal/Bolus Insulin Concept

• Basal Insulin
• Insulin requirement to suppress hepatic glucose
  production between meals
• Bolus Insulin (prandial)
• Insulin requirement to maintain normal glucose
  disposal after eating
• InsulinCHO Ratio 500/(total starting dose)
• Correction Factor 1500/(total starting dose)
• Correction factor in young children 1800/(total
  starting dose)

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LANTUS AND NOVOLOG-POOR MANS PUMP
Lispro
Lispro
Lispro
Insulin Effect
lANTUS
B
L
S
HS
B
Meals
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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.

Adapted from Litton J et al J Pediatr
2002141490-495.
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Better Control and Less Hypoglycemia in Young
Children
HbA1c
Hypoglycemia
Litton J., J Pediatr 2002141490-495.
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Injections Also Fail To Achieve Glycemic Control
Randomized, Prospective Trial of CSII vs. MDI
with Glargine in Children

• Hypoglycemia
• MDI - 5
• CSII - 2
• DKA
• MDI - 0
• CSII - 0
• Preference
• MDI - 4 of 16
• CSII - 14 of 16

HbA1c ()
Adapted from Doyle E Diabetes Care July
2004 Boland E et al Diabetes 2003 52 (Suppl.
1) 192
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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 lt
  0.001).
• Decreased progression to proliferative or severe
  non-proliferative retinopathy by 78 (p lt 0.007).

Adapted from White, N et al, J Pediatr. 2001 Dec
139(6) 804-12.
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Glycemic Memory Sustained Beneficial Effect Of
Prior Intensive Therapy

• 195 patients between the ages of 13 and 17 in
  DCCT
• Relative risk of hypoglycemia lt 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.
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• 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.
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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

Mean HbA1c levels
Adapted from Ahern J et al Pediatr Diabetes.
2002 Mar3(1) 10-5.
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World youngest pumper in 1999 5mo old
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World youngest pumper 2003 10 d old
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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

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Introduction

• Test the feasibility and efficacy of insulin pump
  therapy initiated within the first month of
  diagnosis
• N28 consecutive. mean age 12.1 6.2 years
• Range of start 1-30 days
• None discontinued after up to three year
  follow-up
• 2 sites Cornell Medical Center and Maimonides
  Medical Center

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Hypothesis

• Our hypothesis are
• Patients on pump have better control of their
  blood glucose level
• Better control allows extension of the honey
  moon period

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Rationale and Hypothesis

• Earlier aggressive glucose control leads to lower
  incidence of long-term complications
• Insulin pump therapy resembles physiology more
  closely than multiple daily injections
• Lower incidence of occult and overt serious and
  moderate hypoglycemia
• Would there be benefit to introducing pump
  therapy earlier rather than waiting until further
  insulinopenia sets in?

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Demographics
Range 26 months to 32 years
Average time to pump start 16 days 11 days 3
went straight to pump and 2 started within one
week
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Mean HbA1c Levels Pre and Post Initiation
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HbA1c
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Insulin Burden (U/kg)
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C Peptide AUC-In response to MMTT (Boost)
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Other Significant Findings

• BMI-No significant gains or losses in BMI SD over
  study time
• All patients were self-sufficient within 3
  months

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Conclusions

• Starting patients on insulin pump therapy is a
  viable option at or soon after diagnosis
• Further studies need to be performed to see if
  quality of life and long term complications are
  affected
• Despite the labor intensivity of this approach
  the benefits were clear and patients opted to
  remain on pump therapy after treatment
• Apparent prolongation of the honeymoon

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Candidates for pump therapy

• My Criteria
• Any patient who is willing to start and has
  abilities to learn
• May improve compliance
• Any age adults and children of any age
  (independent users 7-80 y old)
• Particularly non-compliant patients

• Typical Criteria
• Only motivated patients
• only patients who showed good compliance on
  previous regimen
• Adults and children gt 6y old

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ADVERSE EVENTS
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PSYCHOSOCIAL OUTCOMES
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The Yale Experience

• gt 200 children started on pumps over last 5 yrs
• No difference in severe hypoglycemia
• Parents report less mild hypoglycemia

HbA1c HbA1c
Age (yr) pre 3 mos post
lt 7 7.6 6.7
7-12 7.8 7.3
13-18 7.9 7.5
Ahern et al., Journal of Pediatric Endocrinology
and Metabolism 2000, 13(suppl 4)1220.
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Additional Evidence From Yale

• Decreased hypoglycemia
• No change in BMI or TDD
• 98 remained on CSII

Ahern, JAH, et.al. Pediatric Diabetes
2002310-15.
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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 gt 1 yr duration Standard
insulin therapy (2-3 injections/day)

CSII (aspart) n12
Injectiontherapy
MDI (aspart/glargine) n14
Boland et al., Diabetes 2003, 52S1, A45, 192-OR
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Pump Group Achieved Better Control Overall
Changes in HbA1c Levels
8.5
8
7.5
Pump
7
MDI
6.5
Baseline
4 wks
8 wks
12 wks
16 wks
Boland, E. Diabetes 52,(Suppl 1), 2003 Abstract
192.
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More Pump Wearers Achieved HbA1c 6.9
_
lt
Patients Achieving
HbA1c
6.9
lt
Pump Glargine
Boland, E. Diabetes 52,(Suppl 1), 2003 Abstract
192.
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Swedens 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.
.
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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

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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.
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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

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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

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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.

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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

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When meditating over a disease, I never think of
finding a remedy for it, but rather, a means of
preventing it.Louis Pasteur, 1884
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