Basics of Continuous Subcutaneous Insulin Infusion Therapy by KDI8IQ

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									         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

•   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         Discovery of Insulin
                                                                    Artificial
                                                                    Pancreas
   1776         1900s      1921              1977 1978    1999
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

                                                                   43,000
 50,000                                                   35,000
                                                 26,500
                                        20,000
                               15,000
          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%                                52%




Color Key:                            General Type 1
    Pump Therapy                      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
                                                   •   Foot Ulcers
                                                   •   Angina
                                                   •   Heart Attack
                                                   •   Coronary Bypass
                                                       Surgery
                                                   •   Stroke
RISK




                                                   •   Blindness
                            • Albuminuria          •   Amputation
                            • Macular Edema        •   Dialysis
                            • Proliferative        •   Kidney
                              Retinopathy              Transplant
                            • Peridontal Disease
                            • Impotence
                            • Gastroparesis
       • Microalbuminuria   • Depression
       • Mild Retinopathy
       • Mild Neuropathy


       Good                  CONTROL                                 Poor
                                                                DCCT
             Microvascular Risk Reduction With
                    Intensive Treatment
                                                                                       Reduction in
            Complication                                                               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
•   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%                              41%                   42%
       59%                                    59%             58%




   Controlled

   Uncontrolled

Harris MI et al. Diabetes Care. 2000;23:754
                               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

                                                                                        ~40 to >50% have A1C > 8%
                             A1C (%)               8.5                                  NHANES/BRFSS; Harmel et al.



                                                   8.0


             ~30% of type 2 insulin                7.5
             users have A1C <8%
             Harmel et al.
                                                   7.0                <7
                                                                                                      ADA: recommended target
                                                                    <6.5
                                                   6.5
                                                                                                     AACE/ACE: recommended target
                                                                        6
                                                   6.0                                               Upper limit of normal range

                                                   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
Advantages of CSII
  The Goal of Insulin Therapy:
  Attempt to Mimic Normal Pancreatic Function

                                                           B             L    S   HS
                                     160
                                     140
       PLAS MA                       120
      GLUCOS     E
                                     100
        m g /d l
                                        80
                                        60
                                        75
                                        60
  PLAS MA FR  EE                        40
     INS ULIN
                                        30
       u/m l
                                        15
                                           0
                                                     330         1130 1530    1930 2330 0330 0730
                                                                              HOURS
Schade, Skyler, Santiago, Rizza, ―Intensive Insulin Therapy,‖ 1993, p. 131.
Twice-daily Split-mixed Regimens

                                    Regular
                                    NPH
  Insulin Effect




                   B   L   S   HS     B




                                              6-23
Basal Bolus Regimen with Glargine and Lispro

                                     lispro
                                     Glargine
       Insulin Effect




                        B   L   S   HS          B




                                                    6-56
       Continuous Subcutaneous Insulin
                   Infusion
                                  Bolus
                                  Basal
Insulin Effect




                 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
•   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                         9.2                     P=0.0006
                                                       P=0.0006
                                 8.4                                 8.4
                       9               P=0.001         8.2
  Mean                 8
                                       7.7
                                                                                    MDI
 HbA1c%
                                                                                    CSII
                       7

                       6

                            Entire Cohort       MDI              MDI
                                             HbA1c >8.0%      HbA1c >9.0%
 Bell and Ovalle, Endocr Pract
 2000;6:357-60
Improved Control and Less Variability
        With Pump Therapy
         Pump Therapy                                 Multiple Daily Injections
                                  Finger Stick                                         Finger Stick
Glucose (mg/dl)                   Sensor            Glucose (mg/dl)                    Sensor
400                                                 400

350                                                 350

300                                                 300

250                                                 250

200                                                 200

150                                                 150

100                                                 100

50                                                  50
  0                                                   0
          6:00 a.m. 12:00 p.m.
 12:00 a.m.                  6:00 p.m. 12:00 a.m.             6:00 a.m. 12:00 p.m.
                                                     12:00 a.m.                  6:00 p.m. 12:00 a.m.
                    Time (Day)                                          Time (Day)
             Improved Control:
          Decreased Hypoglycemia
                           138
                150



Episodes per 100
100 pt yrs
                                                               39           36
                 50                    22          26


                   0
                       Pre CSII    1 yr       2 yr        3 yr           4 yr
         N=55                       ------------ With CSII------------

Bode et al: Diabetes Care 1996; 19:324-7
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
                            6                                       7
                            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

•   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……
•   Ease of use                •   Training and education
•   Clinical features          •   Insulin delivery system
•   Safety features            •   Patient age
•   Customer service           •   Patient lifestyle
•   Cost of pump               •   Cosmetic issues
•   Insurance coverage
•   Physician/CDE preference
•   Bolus options
•   Number of basal programs
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%




                                                  Discontinued
                                                       3%
     N = 165
     Average Duration = 3.6 years
     Average Discontinuation <1%/yr


Bode, et al.: Diabetes 1998; 47 (Suppl 1): 392.
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                    Extended Bolus
Insulin




                                Insulin




          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




                                          Second Phase
                                         Insulin Secretion
      Insulin




                Time
Dual Wave Bolus vs. Standard Bolus after High Fat Meal


  400
  350
  300
  250                                               Standard Bolus
  200
                                                    Dual Wave
  150                                               Bolus
  100
   50
    0
                                    2



                                              6
        0



                  4



                            8


                                      1



                                                1
     ur



               ur



                         ur


                                   ur



                                             ur
  Ho



            Ho



                      Ho


                                Ho



                                          Ho
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


                   250
Increase (mg/dl)
 Blood Glucose




                   200

                   150

                   100

                   50

                    0
                              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                          Sample Meal
  1 c. orange juice    30 g             2 slices wheat bread       30 g
  2 slices toast       30 g             2 oz. turkey breast
  ½ c. oatmeal         15 g             Lettuce leaf, tomato slice
  1 soft-cooked egg                     1 tsp mayonnaise
  1 tsp margarine                       6-8 3-ring pretzels        15 g
  Coffee & 1 T cream                    2 small choc cookies       15 g
  _____________________                 Diet soda, 16 oz__________
  Total CHO:          75 g              Total CHO:                60 g
  Insulin bolus:    5 units             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:   mg/dl

          Regular:           1500 Rule
          Humalog:           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        • Visit healthcare provider - even if
  always before bed                      feeling well
• Follow hypoglycemia guidelines       • Review log book and pump
                                         settings with physician/CDE
• Follow hyperglycemia guidelines
                                       • 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
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…

•   Poor HbA1c’s            • Shift Work
•   Frequent hypoglycemia   • Insulin Requiring Type
•   Dawn phenomenon           2’s?
•   Pediatrics
•   Pregnancy
•   Gastroparesis
•   Hectic Lifestyle

								
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