Transcript Let’s Get Pumped! Basics of Continuous Subcutaneous

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. Elizabeth’s Hospital, Appleton, WI
Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control Program
Website: www.endocrinology-online.com
Overview
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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
History of Pumps
Best and Banting
Evolution of Diabetes Management
Technologies
Insulin Pump Therapy
Glucose Sensors
BG Meters
Urine Test Strips
Urine Tasting
1776
Discovery of Insulin
1900s
1921
1977 1978
1999
Artificial
Pancreas
First Insulin Pump
(early 1970s)
Early Insulin Pumps
AutoSyringe AS*6c
1979-1980
Lilly Betatron 1983
Present Day Insulin Pumps
U.S. Pump Usage
Total Patients Using Insulin Pumps
200,000
157,000
150,000
120,000
100,000
81,000
60,000
50,000
35,000
15,000
20,000
43,000
26,500
6,600 8,700 11,400
0
'90
'91
'92
'93
'94
'95
'96
'97
'98
'99
2000 2001 2002
How Diabetes Specialists Treat
Their Own Type 1 Diabetes
AADE Membership
ADA Membership
n=229
n=293
60%
Color Key:
Pump Therapy
52%
General Type 1
Population* 6%
Injections
•Industry estimates at time of survey (9/98);
•Graff: Diabetes Educator 2000; 46:460-467
Benefits of Improved
Glycemic Control
Potential Chronic
Complications of Elevated HbA1c
RISK
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• Microalbuminuria
• Mild Retinopathy
• Mild Neuropathy
Good
• Albuminuria
• Macular Edema
• Proliferative
Retinopathy
• Peridontal Disease
• Impotence
• Gastroparesis
• Depression
CONTROL
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Foot Ulcers
Angina
Heart Attack
Coronary Bypass
Surgery
Stroke
Blindness
Amputation
Dialysis
Kidney
Transplant
Poor
DCCT
Microvascular Risk Reduction With
Intensive Treatment
Complication
Reduction in
Relative Risk
Retinopathy
63%
Nephropathy
54%
Neuropathy
60%
Data from the Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986.
Additional Benefits of Improving Glycemic
Control
• Decreased macrovascular changes
– Insulin is NOT atherogenic
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Improved wound healing
Decreased infections
Improved post infarct survival
Minimization of oxidative damage
Treatment Strategies for Diabetes:
Are Patients Achieving Good Control?
Hypertension
Hyperlipidemia
Glycemic control
BP <140/90 mm Hg
LDL-C <130 mg/dL
A1C <7.0
41%
59%
Controlled
Uncontrolled
Harris MI et al. Diabetes Care. 2000;23:754
41%
59%
42%
58%
A1C’s in Clinical Practice
10.0
~20 to >40% have A1C > 9.5%
NHANES/BRFSS; Harmel et al.; NCQA 2000
9.5
9.0
A1C (%)
~40 to >50% have A1C > 8%
8.5
NHANES/BRFSS; Harmel et al.
8.0
~30% of type 2 insulin
users have A1C <8%
Harmel et al.
7.5
7.0
6.5
6.0
<7
ADA: recommended target
<6.5
AACE/ACE: recommended target
6
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
Upper limit of normal range
Advantages of CSII
The Goal of Insulin Therapy:
Attempt to Mimic Normal Pancreatic Function
B
L
S
HS
160
140
PLASMA
GLUCOSE
m g/dl
120
100
80
60
75
60
PLASMA FREE
INSULIN
u/m l
40
30
15
0
330
1130 1530
Schade, Skyler, Santiago, Rizza, “Intensive Insulin Therapy,” 1993, p. 131.
1930 2330 0330 0730
HOURS
Twice-daily Split-mixed Regimens
Insulin Effect
Regular
NPH
B
L
S
HS
B
6-23
Basal Bolus Regimen with Glargine and Lispro
lispro
Insulin Effect
Glargine
B
L
S
HS
B
6-56
Continuous Subcutaneous Insulin
Infusion
Bolus
Insulin Effect
Basal
B
L
S
HS
B
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; 24:326-9
Advantages of Pump Therapy
• Improved blood glucose control
– Improved AIC’s
– Decreased hypoglycemia and hyperglycemia
– Delay in incidence and progression of complications
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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
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
10
8.4
9
Mean
HbA1c%
P=0.0006
9.2
P=0.0006
P=0.001
8.2
8.4
7.7
8
MDI
CSII
7
6
Entire Cohort
Bell and Ovalle, Endocr Pract
2000;6:357-60
MDI
HbA1c >8.0%
MDI
HbA1c >9.0%
Improved Control and Less Variability
With Pump Therapy
Pump Therapy
Glucose (mg/dl)
Multiple Daily Injections
Finger Stick
Sensor
Glucose (mg/dl)
Finger Stick
Sensor
400
400
350
350
300
300
250
250
200
200
150
150
100
100
50
50
0
12:00 a.m.6:00 a.m. 12:00 p.m.6:00 p.m. 12:00 a.m.
Time (Day)
0
12:00 a.m.6:00 a.m. 12:00 p.m.6:00 p.m. 12:00 a.m.
Time (Day)
Improved Control:
Decreased Hypoglycemia
150
138
Episodes per 100
100 pt yrs
50
22
26
39
36
0
Pre CSII
N=55
1 yr
2 yr
3 yr
------------ With CSII------------
Bode et al: Diabetes Care 1996; 19:324-7
4 yr
Benefits of
Decreased Hypoglycemia
• Reduced risk of diabetic encephalopathy
• Reduced risk of accidents and death
• Improved hypoglycemia awareness
Improved
Hypoglycemia 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 1997;46: 1172-1181
(episodes / 100 pt years)
Diabetic Ketoacidosis
16
14
15
12
10
8
7
6
4
2
0
Pre-CSII
Post-CSII
Bode, BW, Diabetes Care 19:324-7, 1996.
Improved Health Status with CSII
Improved
82%
Worse
2%
No Change
16%
N=886
Self-Reported Data
Association for Insulin Pump Therapy, Diabetes 1991:40:#1807
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 11:1998: 26-32.
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
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
Challenges of Pump Therapy
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Learning curve
Risk of DKA
Possible weight gain
Frequent monitoring required
Potential site infections
Inconvenience in wearing pump
Education and follow-up required
Cost
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.
Choosing a Pump . . .
Some things to consider……
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Ease of use
Clinical features
Safety features
Customer service
Cost of pump
Insurance coverage
Physician/CDE preference
Bolus options
Number of basal programs
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Training and education
Insulin delivery system
Patient age
Patient lifestyle
Cosmetic issues
Indications for Pump
Therapy
Criteria for Selection of a Pump Candidate
Clinical Indications:
• Inadequate glucose control OR
HbA1c >7.0% with MDI regimen
• Hypoglycemia unawareness
• Recurrent hypoglycemia
• Dawn phenomenon
• Preconception and pregnancy
• Gastroparesis or other complications
• Post-renal transplant
Patient Success Characteristics:
• Motivated
• Realistic expectations
• Ability to manage diabetes—MDI, 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
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
Current Continuation Rate
Continuous Subcutaneous Insulin Infusion (CSII)
Continued
97%
N = 165
Average Duration = 3.6 years
Average Discontinuation <1%/yr
Bode, et al.: Diabetes 1998; 47 (Suppl 1): 392.
Discontinued
3%
Beginning Insulin Pump Therapy
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
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
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.
Establishing Starting
Basal and Bolus Doses
Pre-Pump Dose
Total Daily Dose
(~70-75% of prior insulin regimen TDD)
~50%
~50%
Basal*
Bolus*
Usually divided into 3 premeal doses
*Range: 40 to 60%
(depending on number and size of meals)
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 >70% /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.
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.
Basal Rate Calculation
• May need to use 60% or higher of the TDD
for insulin resistance:
Teens
Type 2
Dawn phenomenon
Which basal rate to start with??
• Most clinicians prefer to initiate a conservative basal rate.
• It’s always better if the patient’s blood glucose values run slightly
higher than too low during pump initiation.
• It’s easier to increase a basal rate gradually by 0.1 u/hr.
Fine Tuning: Basal Rate
• Monitor BG pre-meal, post-meal, bedtime, 12am, and
2-4am
• We assess basal insulin by fasting and premeal BG’s
• 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
Bolus Insulin
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
Calculation of Premeal Bolus Doses
Methods
1.
Use the patient’s pre-pump insulin-to carb ratio
2.
Formula: 500 Rule
3.
Weight based Method
* Bode
et al: Diabetes Care 1994: 19: 324-7
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 . . .
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
Determination of Insulin to Carb Ratio: Method 3
Weight (lb)
Insulin u: CHO gm *
100-109
1: 16
110-129
1: 15
130-139
1: 14
140-149
1: 13
150-169
1: 12
170-179
1: 11
180-189
1: 10
190-199
1: 9
200+
1: 8
Weight Based Method
*Walsh, Pumping Insulin,
2nd
ed.
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)
Normal vs. Extended Bolus
Normal Bolus
Insulin
Insulin
Extended Bolus
Time
Time
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: 30–50% of total bolus
Second bolus:
– Set an Extended Bolus
OR
– Bolus remainder 2 to 4 hours later
Split or Dual Wave Bolus
First Phase Insulin
Secretion
Insulin
Second Phase
Insulin Secretion
Time
Dual Wave Bolus vs. Standard Bolus after High Fat Meal
Standard Bolus
6
Ho
ur
1
2
Ho
ur
1
Ho
ur
8
Dual Wave
Bolus
Ho
ur
4
Ho
ur
0
400
350
300
250
200
150
100
50
0
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
Carbohydrate Counting
Macronutrient Conversion to Blood
Glucose
Glucose Elevations per Carbohydrate
Grams
Each gram of carbohydrate raises glucose by 3-4 mg/dl
Blood Glucose
Increase (mg/dl)
250
200
150
100
50
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5
15
45
Carbohydrate grams ingested
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
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
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
Correction Boluses
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
Insulin Sensitivity Factor
Use to  high blood glucose
1 unit of insulin will  blood glucose by:
Regular:
Humalog:
mg/dl
1500 Rule
1800 Rule
1500 or 1800 divided by TDD= amount of blood glucose
lowered by 1 unit insulin
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
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
Preventing Hypoglycemia
Preventing Hypoglycemia
• Check BG 4-6 times per day
• Carry glucose tablets
• Have Glucagon Kit available
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
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
Preventing
Hyperglycemia and DKA
Preventing Hyperglycemia and DKA
• Monitor BG 4-6 times per day
• Use Correction Boluses when appropriate
• Change infusion set every 2-3 days
Hyperglycemia Treatment Guidelines
The 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
Follow-Up: The Patient’s Role
Every Day
Every 3 months
• Check BG 4-6 times a day, and
always before bed
• Follow hypoglycemia guidelines
• Follow hyperglycemia guidelines
• Visit healthcare provider - even if
feeling well
• Review log book and pump
settings with physician/CDE
• Get a HbA1c
Every month
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Review DKA prevention
Check BG
- 3am (overnight)
- 1 and/or 2-hour post-meal BG for all meals on a given day
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
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
Consider Pump Therapy…
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Poor HbA1c’s
Frequent hypoglycemia
Dawn phenomenon
Pediatrics
Pregnancy
Gastroparesis
Hectic Lifestyle
• Shift Work
• Insulin Requiring Type
2’s?