Basics of Continuous Subcutaneous Insulin Infusion Therapy

1
Basics of Continuous Subcutaneous Insulin
Infusion Therapy

• Thomas Repas D.O.
• Diabetes, Endocrinology and Nutrition Center,
  Affinity Medical Group, Neenah, Wisconsin
• Member, Inpatient Diabetes Management Committee,
  St. Elizabeths Hospital, Appleton, WI
• Member, Diabetes Advisory Group, Wisconsin
  Diabetes Prevention and Control Program

Website www.endocrinology-online.com
2
Overview

• History of insulin pumps
• Benefits of improved glycemic control
• Advantages of insulin pump therapy
• Indications for pump therapy
• Beginning insulin pump therapy (basal and bolus
  dosing)
• Carbohydrate Counting
• Hypoglycemia and hyperglycemia prevention
• Conclusions

3
History of Pumps
4
Best and Banting
5
Evolution of Diabetes Management Technologies
Glucose Sensors
Insulin Pump Therapy
BG Meters
Urine Test Strips
Discovery of Insulin
Urine Tasting
ArtificialPancreas
1921
1900s
1999
1978
1977
1776
6
First Insulin Pump (early 1970s)
7
Early Insulin Pumps
8
AutoSyringe AS6c1979-1980
9
Lilly Betatron 1983
10
Present Day Insulin Pumps
11
U.S. Pump Usage Total Patients Using Insulin Pumps
12
How Diabetes Specialists Treat Their Own Type 1
Diabetes
General Type 1 Population
Color Key
6
Pump Therapy
Injections

• Industry estimates at time of survey (9/98)
• Graff Diabetes Educator 2000 46460-467

13
Benefits of Improved Glycemic Control
14
Potential ChronicComplications of Elevated HbA1c

• Foot Ulcers
• Angina
• Heart Attack
• Coronary Bypass
• Surgery
• Stroke
• Blindness
• Amputation
• Dialysis
• Kidney
• Transplant

RISK

• Albuminuria
• Macular Edema
• Proliferative
• Retinopathy
• Peridontal Disease
• Impotence
• Gastroparesis
• Depression

• Microalbuminuria
• Mild Retinopathy
• Mild Neuropathy

• CONTROL

Good
Poor
15
DCCTMicrovascular Risk Reduction With Intensive
Treatment
Data from the Diabetes Control and Complications
Trial Research Group. N Engl J Med.
1993329977-986.
16
Lifetime Benefits of EffectiveIntensive Therapy
(DCCT)

• Gain of 15.3 years of complication free living
  compared to conventional therapy
• Gain of 5.1 years of life compared to
  conventional therapy

DCCT Study Group, JAMA 19962761409-1415.
17
Additional Benefits of Improving Glycemic Control

• Decreased macrovascular changes
• Insulin is NOT atherogenic
• Improved wound healing
• Decreased infections
• Improved post infarct survival
• Minimization of oxidative damage

18
Treatment Strategies for DiabetesAre Patients
Achieving Good Control?
Glycemic control
Hypertension
Hyperlipidemia
BP lt140/90 mm Hg
LDL-C lt130 mg/dL
A1C lt7.0
41
41
42
58
59
59
Controlled
Uncontrolled
Harris MI et al. Diabetes Care. 200023754
19
A1Cs in Clinical Practice
10.0
9.5
9.0
8.5
A1C ()
8.0
7.5
7.0
6.5
6.0
5.5
ADA. Diabetes Care 2003 26(S1)S33-S50 ACE
Consensus Conference on Guidelines for Glycemic
Control. Endocrine Practice, 2002 HEDIS 2000.
Washington National Committee for Quality
Assurance, 1999 State of Managed Care Quality.
National Committee for Quality Assurance, 2000
20
Advantages of CSII
21
The Goal of Insulin TherapyAttempt to Mimic
Normal Pancreatic Function
Schade, Skyler, Santiago, Rizza, Intensive
Insulin Therapy, 1993, p. 131.
22
Twice-daily Split-mixed Regimens
Regular
NPH
Insulin Effect
B
S
L
HS
B
6-23
23
Basal Bolus Regimen with Glargine and Lispro
lispro
Glargine
Insulin Effect
B
S
L
HS
B
6-56
24
Continuous Subcutaneous Insulin Infusion
Bolus
Basal
Insulin Effect
B
S
L
HS
B
25
Pharmacokinetics of CSII vs MDI

• Uses only immediate acting insulin
• More predictable absorption
• Uses one injection site
• Reduces variations in absorption
• Eliminates most of the subcutaneous insulin depot
• Closest match with physiologic needs

Lauritzen Diabetologia 1983 24326-9
26
Advantages of Pump Therapy

• Improved blood glucose control
• Improved AICs
• Decreased hypoglycemia and hyperglycemia
• Delay in incidence and progression of
  complications
• Precise dosage delivery
• Improved control for pre-conception and pregnancy
• Management of dawn phenomenon
• Increased flexibility in lifestyle
• Improved control during exercise
• Improved gastroparesis management

27
Trial Evidence CSII versus MDI use in routine
clinical practice

• Population Comparison of glycemic control in 58
  patients while on MDI x 3yrs and subsequent CSII
  x 3yrs
• Methods Retrospective, observational cohort
  study of patients with Type 1 diabetes

10.0
P0.0006
10 9 8 7 6
9.2
P0.0006
8.4
8.4
8.2
P0.001
7.7
Mean HbA1c
MDI
CSII
MDI HbA1c gt9.0
MDI HbA1c gt8.0
Entire Cohort
Bell and Ovalle, Endocr Pract 20006357-60
28
Improved Control and Less Variability With Pump
Therapy
Pump Therapy
Multiple Daily Injections
Finger Stick
Finger Stick
Sensor
Sensor
1200 a.m.
600 a.m.
1200 p.m.
600 p.m.
1200 a.m.
1200 a.m.
600 a.m.
1200 p.m.
600 p.m.
1200 a.m.
Time (Day)
Time (Day)
29
Improved ControlDecreased Hypoglycemia
Episodes per 100 pt yrs
N55
Bode et al Diabetes Care 1996 19324-7
30
Benefits of Decreased Hypoglycemia

• Reduced risk of diabetic encephalopathy
• Reduced risk of accidents and death
• Improved hypoglycemia awareness

31
ImprovedHypoglycemia Awareness

• Meticulous glycemic control reduced hypoglycemia
  events from 20 to 2 per month in this study of
  21 patients
• Glycemic thresholds for hypoglycemia symptoms
  normalized in all groups
• Partial recovery of the counterregulatory response

Fanelli Diabetes 199746 1172-1181
32
Diabetic Ketoacidosis
(episodes / 100 pt years)
Bode, BW, Diabetes Care 19324-7, 1996.
33
Improved Health Status with CSII
N886 Self-Reported Data
Association for Insulin Pump Therapy, Diabetes
1991401807
34
Advantages of Pump Therapy in Pregnancy

• Mimics normal physiology
• Decreases glucose excursions
• Reduces hypoglycemia
• Provides insulin regimen individualization
• Improves management of morning sickness
• Increase lifestyle flexibility

Jornsay, DL. CSII Therapy During Pregnancy.
Diabetes Spectrum 111998 26-32.
35
Children

• Recent studies show benefits for under 12 years
  of age
• Prevention and reduction of night-time
  hypoglycemia
• Ability to accommodate variable appetites and
  eating patterns
• Effective and safe with parental
  education/control/supervision

Buckingham, B Kaufman, F ADA 61st Scientific
Sessions, 2001
36
Pump Therapy in Type 2 diabetes

• Reduces glucose toxicity
• Decreases insulin resistance
• Restores sensitivity to oral agents and diet
• Often can result in reduced total daily insulin
  needs

• Must meet same criteria as Type 1

Ilkova et al., Diabetes Care 1997, vol 20 p
1353. Glaser,1985 Garvey, 1985 Scarlett,1997
37
Challenges of Pump Therapy

• Learning curve
• Risk of DKA
• Possible weight gain
• Frequent monitoring required
• Potential site infections
• Inconvenience in wearing pump
• Education and follow-up required
• Cost

38
Cost and Insurance

• A pump typically lists for close to 5000.
• Pump supplies average 1,200 to 1,600 per year!
• Many insurance companies cover all or most of
  this cost.

39
Choosing a Pump . . .
Some things to consider

• Ease of use
• Clinical features
• Safety features
• Customer service
• Cost of pump
• Insurance coverage
• Physician/CDE preference
• Bolus options
• Number of basal programs

• Training and education
• Insulin delivery system
• Patient age
• Patient lifestyle
• Cosmetic issues

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Indications for Pump Therapy
41
Criteria for Selection of a Pump Candidate

• Clinical Indications
• Inadequate glucose control OR
• HbA1c gt7.0 with MDI regimen
• Hypoglycemia unawareness
• Recurrent hypoglycemia
• Dawn phenomenon
• Preconception and pregnancy
• Gastroparesis or other complications
• Post-renal transplant

42
Patient Success Characteristics

• Motivated
• Realistic expectations
• Ability to manage diabetesMDI, frequent SMBG and
  interpretation of results
• Uses carbohydrate counting effectively
• Family support
• Financial resources
• Psychological and emotional stability
• Intellectual, physical, and technical ability to
  use the pump

43
Contraindications to Pump Therapy

• Insufficient motivation to

• Perform frequent (4 daily) SBGM tests
• Learn and practice CHO counting
• Initially document activities of daily living
• Adjust to recommended medical therapy

44
Current Continuation Rate Continuous Subcutaneous
Insulin Infusion (CSII)
N 165 Average Duration 3.6 years Average
Discontinuation lt1/yr
Bode, et al. Diabetes 1998 47 (Suppl 1) 392.
45
Beginning Insulin Pump Therapy
46
Basal Rate of Insulin

• Mimics fasting insulin secretion of a normal
  pancreas
• Continuous flow of insulin
• Replaces the intermediate or long acting insulin
  of MDI regimen
• Adjust to match metabolic need for insulin under
  fasting conditions

47
Bolus Insulin

• Simulates mealtime insulin secretion of normal
  pancreas
• Programmed for delivery by patient
• Replaces short acting insulin of MDI regimen
• Is given as needed by patient premeal or to
  correct for hyperglycemia

48
Pump Therapy Insulin Doses
Basal rate 40 50 TDD Bolus totals 50
60 TDD
Remember Always Individualize!
American Diabetes Association, Intensive Diabetes
Management. 2nd ed. Alexandria, VA 1998. Bode,
BW. The Insulin Pump Therapy Book Insights
From the Experts. Sylmar, CA MiniMed
Technologies 1995 49-56, 85-93.
49
Establishing StartingBasal and Bolus Doses
Pre-Pump Dose
Total Daily Dose (70-75 of prior insulin
regimen TDD)
50 Basal
50 Bolus
Usually divided into 3 premeal doses (depending
on number and size of meals)
Range 40 to 60
50
Total Daily Dose (75 pre-pump dose)
Example TDD (Total Daily Dose) 27 u/24
hrs 27 u x .75 20.25 u TDD Note If pre-pump
dose of fast acting is gt70 /24 hrs, may need
further reduction.
Bode, BW. The Insulin Pump Therapy Book
Insights From the Experts. Sylmar, CA
MiniMed Technologies, 1995 49-56, 85-93.
51
Basal Rate Calculation 40 50 TDD
40 50 of TDD 24 hours u/hr Example TDD
48 u x 0.4 19.2 0.8 u/hr 24
American Diabetes Association, Intensive Diabetes
Management. 2nd ed. Alexandria, VA 1998. Bode,
BW. The Insulin Pump Therapy Book Insights
From the Experts. Sylmar, CA MiniMed
Technologies 1995 49-56, 85-93.
52
Basal Rate Calculation

• May need to use 60 or higher of the TDD for
  insulin resistance
• Teens
• Type 2
• Dawn phenomenon

53
Which basal rate to start with??

• Most clinicians prefer to initiate a conservative
  basal rate.
• Its always better if the patients blood glucose
  values run slightly higher than too low during
  pump initiation.
• Its easier to increase a basal rate gradually by
  0.1 u/hr.

54
Fine Tuning Basal Rate

• Monitor BG pre-meal, post-meal, bedtime, 12am,
  and 2-4am
• We assess basal insulin by fasting and premeal
  BGs
• Test fasting BG with skipped meals
• Adjust nighttime basal based on 2-4am and
  pre-breakfast BG
• Usually adjust basal by 0.1 u/hr to avoid
  over-correction

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Bolus Insulin
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Bolus Dose Insulin

• Premeal boluses
• Taken before meals
• Covers mealtime carbohydrate intake
• Prevents postprandial hyperglycemia
• Correction or supplementation boluses
• Used to Correct and treat hyperglycemia
• May be given alone between meals for
  hyperglycemia
• May be given to supplement already scheduled
  insulin to cover premeal hyperglycemia

60
Calculation of Premeal Bolus Doses

• Methods
• Use the patients pre-pump insulin-to carb ratio
• Formula 500 Rule
• Weight based Method

Bode et al Diabetes Care 1994 19 324-7
61
Determination of Insulin to Carb Ratio Method 1

• EXAMPLE Pre-pump 1 unit of insulin 15 gm carb
• Note 1 unit 15 gm is often a safe starting
  point
• for most patients . . .

62
Determination of Insulin to Carb Ratio Method 2

• Use the 500 Rule
• Divide 500 by TDD 1 unit insulin to ___ gm CHO
  as bolus
• EXAMPLE 500 34 u 15
• Bolus ratio is 1 u insulin 15 gm CHO

63
Determination of Insulin to Carb Ratio Method 3
Weight Based Method
Walsh, Pumping Insulin, 2nd ed.
64
Extended Bolus Option

• Equally divides, or spreads one bolus amount
  over a specific number of hours
• Use for
• long meals (parties or holidays)
• high fat meals (pizza)
• delayed digestion (gastroparesis)

65
Normal vs. Extended Bolus
Normal Bolus

• Extended Bolus

Insulin
Insulin
Time
Time
66
Split or Dual Wave Bolus Option

• Patient divides bolus into 2 separate bolus
  amounts
• Use for continuous snacking, high fat meals or
  snacks
• Initial bolus 3050 of total bolus
• Second bolus
• Set an Extended Bolus
• OR
• Bolus remainder 2 to 4 hours later

67
Split or Dual Wave Bolus
First Phase Insulin Secretion
Second Phase Insulin Secretion
Insulin
Time
68
Dual Wave Bolus vs. Standard Bolus after High Fat
Meal
69
Pump Therapy Initiation Insulin Carb Bolus Tips

• Use pre-pump MDI insulin-to-CHO ratio for
  boluses, if has been successful
• Try to keep CHO amount consistent at meals
  (consume same amount of CHO for each breakfast,
  each lunch, etc.)
• Avoid excessive protein, high fat content meals,
  alcohol, and foods not usually consumed

70
Carbohydrate Counting
71
What Is Carbohydrate Counting?

• Simple meal planning method . . .
• Preferred meal planning approach used in the DCCT
• Widely used throughout Europe
• Result of advances in diabetes management and is
  research-based

72
Why Count Carbs?

• It works
• Increases flexibility in food choices and the
  amounts of foods consumed
• Easy to understand
• Well-accepted

73
Macronutrient Conversion to Blood Glucose
74
Glucose Elevations per Carbohydrate Grams Each
gram of carbohydrate raises glucose by 3-4 mg/dl
Blood Glucose Increase (mg/dl)
Carbohydrate grams ingested
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Carbohydrate Counting

• Benefits
• Allows for variation in appetite and preferences
• Increases variety of food choices
• Can be used to match insulin bolus doses to food
  intake

76
Carb Counting and Insulin Bolusing
Insulin-to-Carb Ratio EXAMPLE 1 unit insulin
15 grams CHO

• Sample Meal
• 1 c. orange juice 30 g
• 2 slices toast 30 g
• ½ c. oatmeal 15 g
• 1 soft-cooked egg
• 1 tsp margarine
• Coffee 1 T cream
• _____________________
• Total CHO 75 g
• Insulin bolus 5 units

• Sample Meal
• 2 slices wheat bread 30 g
• 2 oz. turkey breast
• Lettuce leaf, tomato slice
• 1 tsp mayonnaise
• 6-8 3-ring pretzels 15 g
• 2 small choc cookies 15 g
• Diet soda, 16 oz__________
• Total CHO 60 g
• Insulin bolus 4 units

77
Fine Tuning Meal Bolus Doses

• Adjust bolus based on post-meal BGs
• Carbohydrate counting or pre-determined meal
  portion
• Individualize insulin to carbohydrate dose or
  insulin to premeal dose

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Correction Boluses
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Correction Bolus Insulin

• To be taken to correct for hyperglycemia
• Based on insulin sensitivity factor
• Goal is for correction bolus to lower blood
  glucose to within 30 to 50 mg/dl of target value

81
Insulin Sensitivity Factor
Use to ? high blood glucose

• 1 unit of insulin will ? blood glucose by
  mg/dl
• Regular 1500 Rule
• Humalog 1800 Rule
• 1500 or 1800 divided by TDD amount of
  blood glucose lowered by 1 unit insulin

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Insulin Sensitivity Factor

• EXAMPLE
• TDD is 34 units
• 1500 Rule 1500 34 44
• 1 unit of Regular ? bg 44 mg/dl
• 1800 Rule 1800 34 53
• 1 unit of Humalog ? bg 53 mg/dl

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Unused Insulin Rule
Lispro is gone in approx. 3 4 hrs Decrease
bolus 30 each hour 1st hour 70
remaining 2nd hour 40 remaining 3rd hour
10 remaining 4th hour 0 remaining
Walsh. PA. Roberts. R Pumping Insulin. 3rd ed.
San Diego, Calif Torrey Pines Press 2000
85
Preventing Hypoglycemia
86
Preventing Hypoglycemia

• Check BG 4-6 times per day
• Carry glucose tablets
• Have Glucagon Kit available

87
Preventing Hypoglycemia

• Test before driving and ideally 1 hour later
  (target over 100 mg/dl)
• Perform two SMBG 30 minutes apart prior to
  bedtime (confirming rising or falling BG)
• When drinking alcohol, perform SMBG hourly
• With exercise, perform SMBG pre- and
  post-exercise
• If hypoglycemia episodes persist, raise target
  glucose levels

88
Hypoglycemia Treatment Guidelines

• The Rule of 15
• If BG is 70 mg/dl or below
• Treat with 15 grams of carbohydrates (glucose
  tabs)
• Check BG in 15 minutes, and if not above 70
  mg/dl, repeat treatment
• Glucagon
• Current emergency kit readily available and
  knowledgeable person trained to administer

89
PreventingHyperglycemia and DKA
90
Preventing Hyperglycemia and DKA

• Monitor BG 4-6 times per day
• Use Correction Boluses when appropriate
• Change infusion set every 2-3 days

91
Hyperglycemia Treatment GuidelinesThe Key to
Preventing DKA

• 1st BG over 250 mg/dl
• Take a correction bolus via pump, check again in
  1 hour
• 2nd BG over 250 mg/dl
• Take correction bolus by syringe and change
  infusion set, review pump, check BG again in 1
  hour
• Call physician immediately if nausea and vomiting
  and/or ketones are present

92
Follow-Up The Patients Role

• Every Day
• Check BG 4-6 times a day, and always before bed
• Follow hypoglycemia guidelines
• Follow hyperglycemia guidelines

• Every 3 months
• Visit healthcare provider - even if feeling well
• Review log book and pump settings with
  physician/CDE
• Get a HbA1c

• Every month
• Review DKA prevention
• Check BG
• 3am (overnight)
• 1 and/or 2-hour post-meal BG for all meals on a
  given day

93
Conclusion

• Pump Therapy is becoming widely recognized as the
  best way to treat insulin requiring diabetes
• It is now considered standard of care in
  appropriate patients
• Pump Therapy is not difficult to implement in a
  medical practice
• When implantable continuous glucose sensors are
  perfected and become readily available pumps
  will become an even greater tool

94
Implantable Pumps Coming Soon?

• Continuous intraperitoneal insulin delivery
  provides physiologic insulin absorption
• Negative pressure insulin reservoir special
  U-400 insulin refilled every 2 to 3 months
• Small, programmer communicates with the pump
  using RF telemetry.

In the US implantable insulin pumps are
investigational only
95
Consider Pump Therapy

• Poor HbA1cs
• Frequent hypoglycemia
• Dawn phenomenon
• Pediatrics
• Pregnancy
• Gastroparesis
• Hectic Lifestyle

• Shift Work
• Insulin Requiring Type 2s?