Type 1 Diabetes: Multiple Dose Injections

and Pump Therapy

Joe Largay, PAC, CDEClinical InstructorDepartment Of MedicineUniversity Of North Carolina

jlargay@med.unc.edu

Learning Objectives:

• Relate physiologic insulin replacement to basal/prandial therapy with Multi-dose Injections (MDI) and insulin pump therapy

• Compare available insulin regimens• Explain the benefits of insulin pump therapy

and identify ideal pump candidates• Discuss how to integrate diabetes

management software into clinical practice

The Blood Sugar Fairy

How Your Body Secretes Insulin

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Bolus InsulinBasal Insulin

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Bolus InsulinBasal Insulin

Time

Conventional Insulin TherapyBenefits Two injections per day

(no mealtime bolus injections)

Doses are fixed (no calculations needed)

Disadvantages No flexibility in diet No flexibility in schedule

Doses do not match how a pancreas maintains the insulin/glucose balance

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Schematic representation only.

Multiple Daily Injection (MDI) Therapy

Benefits Provides intensive glucose

control More flexible lifestyle Basal and bolus rates can be

calculated separately

Disadvantages

Four to eight injections per day in several different areas of your body

Limited to one or two basal doses per day

Complicated math calculations Bolus doses not always accurate

due to math and guessingLantus® or Levemir®

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Bolus Insulin

Basal Insulin

Humalog®, Novolog® or

Apidra®

Schematic representation only. Humalog is a registered trademark of Eli Lilly and Company. Novalog and Levemir are registered trademarks of Novo Nordisk A/S.Apidra and Lantus are registered trademarks of Sanofi-Aventis US, LLC.

MDI with long acting Basal and Rapid-Acting Insulin

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The Basal-Bolus Insulin Concept

• Basal insulin– Controls glucose production between meals and overnight

– Nearly constant levels

– 50% of daily needs

• Bolus insulin (mealtime or prandial)– Limits hyperglycemia after meals

– Immediate rise and sharp peak at 1 hour postmeal

– 10% to 20% of total daily insulin requirement at each meal

• Ideal insulin replacement therapy– Combines different insulins, each with specific profiles

Human Insulins and AnaloguesTypical Times of Action

Insulin Onset of Duration ofPreparations Action Peak ActionAspart / glulisine orlispro ~15 minutes 1–2 hours 4–6 hours

Human regular 30–60 minutes 2–4 hours 6–8 hours

Human NPH/lente 2–4 hours 4–10 hours 12–20 hours

Detemir 2 hours 6-10 hours 18–20 hours

Glargine 2–4 hours Flat ~24 hours

T1DM Insulin Needs

• Total Daily Insulin Need: ~0.6-0.8 u/kg Total Daily Dose (TDD)

• Basal: ~ 0.3 u/kg (~ 40-50% of TDD)

• Bolus: ~ 50-60% of TDD

• Correction Factor: utilizes insulin sensitivity factor(ISF) to correct for high glucose

Carbohydrate Counting

•Definition of carb counting

•Sources of carbohydrate

•Portion size

•Insulin to carbohydrate ratio

Insulin:Carbohydrate Ratio

Based on Weight

weight (lbs.) ratio (units/gram CHO)

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

THE 450 RULE

Total daily dose grams of cho

covered by 1 unit

20 23

25 18

30 15

35 13

40 11

50 9

60 8

CHO content of a typical meal

& corresponding insulin dosage

Cheeseburger….…………………………..…30

Potato Chips…………………………………..17

Cookie……………………………………….…20

Apple…………………………………………...15

Diet Coke………………………………….…….0

Total CHO = 82

• 1:15 insulin/CHO ratio = 5.5 units

Rule of 1700 Correction Factor or

Insulin Sensitivity Factor

1700 divided by Total Daily Dose Insulin equals the amount you would expect 1 unit of insulin to lower glucose

Example: TDD ~48u

1700/48= 35

So this patient’s Insulin Sensitivity = 35

ISF 0f 35Current BG level before meal

Amount of insulin to add to meal bolus

< 80 -1

80 120 0

121 156 1

157 192 2

193 228 3

229 264 4

265 300 5

Pre meal BG=202Eating 50 gm CHO

CHO ratio 1:10Meal = 5u

CF=3uTotal Insulin Dose=8u

Continuous Insulin Infusion Pumps

Varying Insulin Needs Throughout the Day

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age 3-10 age 11-20age 21-60 age > 60

Lantus® or Levemir®

Scheiner G, Boyer BA. Diabetes Res Clin Pract.2005;69:14-21.Lantus is a registered trademark of Sanofi aventis Pharmaceuticals, Inc. Levemir is a registered trademark of Novo Nordisk A/S.

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Insulin Pump TherapyInsulin pump therapy more closely mimics a healthy pancreas than injections

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Normal Insulin SecretionInsulin Pump Delivery

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Schematic representation only.

CSII PumpAdvantage-• most physiologicphysiologic insulin replacement available• more predictablepredictable insulin absorption• acute adjustments in basal rate with temporary basal

setting• Can match the insulin to carb more accurately with bolus

calculator• reduced risk for hypoglycemia• ability to stabilize pre exercise glucose • Requires one “injection” every 3 days

Disadvantage-• Must wear pump 24 hours a day (does allow disconnect for

short periods)• Potential problems if not monitoring regularly

Individualized Insulin Therapy

Dawn phenomenon Low glucose levels

at night

Slow digestion

Programmable Settingsfor Specific Medical Needs

Programmable Settingsfor Lifestyle Flexibility

Meal and snack timing

Food choices

Sick days

Exercise

Weekday vs weekend

Shiftwork

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Pump Basics

Animas

Medtronic

The OmniPod System Insulin pump therapy with two wireless

components• Fully Integrated 2 Part Design

• User Interface• Full Text Navigation

• Set-up Wizard

• Reduced Complexity

• Automated Cannula Insertion• No Sharps

• Reservoir Volume Feedback

• Occlusion Sensing

• Self Priming

Valeritas' V-Go™

• Patient peels protective liner from the adhesive backing.

• Start button is pushed, micro-needle is inserted and basal insulin starts.

• Can be attached to abdomen, arm or thigh.

• Wearer presses the bolus button and a click will be heard to indicate bolus has been delivered.

• Replaced every 24 hours.

Pieces and Parts

BLADDER

Insertion Device(optional)

Insulin Pump

+

Reservoir

+

Infusion Set

+

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Infusion Sets

• Angle of insertion (straight vs angled)

• Canula length (5-9 mm)

• Plastic vs. steel

• Tubing length (18”-43”)

Infusion Sets

SilhouetteSilhouette

Silhoutte Silhoutte ComfortComfort

Medtronic Quick SetMedtronic Quick Set

Rapid-DRapid-D

Straight/AngledStraight/Angled 90 degree90 degree

Polyfin

(steel)

Polyfin

(steel)

Animas Inset

Infusion Set Inserters

Medtronic Medtronic Quik-serterQuik-serter

Animas Inset

Medtronic Mio

Location, Location, LocationBy Absorption Rate

Abdomen

Arms

Thighs

Buttocks

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Change It Up

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Wear It Well

Waist Clip Belt Loop Clip Case Velcro Waist Case

Velcro Thigh Wrap Supplies Travel Case Children’s Case

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Patient Selection Criteria

• Is motivated and monitoring

• Wants to improve glucose control

• Desires to live a more normal life

• Currently using an MDI regimen

• Has family support

• Has realistic expectationsTanenberg: The Insulin Pump Book, MiniMed 1995: 21-30

Transitioning To a Pump• 2 hour initial appointment

• Daily to weekly follow up with CDE in first few weeks

• Control may not improve in first month

• Hold basal insulin day before switching to pump

• Patient will need new prescription for vials if currently using pens

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Variable Wave Boluses

Normal BolusThe whole bolus is delivered at one time

Extended Bolus (Square Wave)The bolus is deliveredover time

Combination Bolus (Dual Wave)A combination of both a normal and a square bolus

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Time

0 5 min … 1 hr. 2 hrs. 3 hrs. 4 hrs.

Time

0 5 min … 1 hr. 2 hrs. 3 hrs. 4 hrs.

Time

0 5 min … 1 hr. 2 hrs. 3 hrs. 4 hrs.

Smart Pumps

• Offer more precise calculations based on formulas and algorithms that help determine insulin dose based on:1. Carbohydrate intake

2. Current glucose level

3. Insulin on board

Today’s Smart Pumps

• Easy dose calculations with Carb Factor and Correction Factor

• Precise insulin dosing (0.025 units) to allow basal rates to be set up for Dawn Phenomenon, etc.

• Tracks insulin on board to avoid insulin stacking

• Reminders for missed meal bolus & BG post meal

Definition: Insulin on Board (IOB)

The amount of insulin still active at a given time after a bolus

Insulin Remaining vs. Time

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Rapid ActingRegular

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PROTEIN &/OR FAT SENSITIVE?

Examples 1Meal : 1:15 insulin:CHO ratio

•grilled chicken breast

•10 french fries

•2cups salad with 1/4 cup ranch dressing

•1/4 slice coconut cream pie

Dual wave bolus: 4 units now and 3 units over 1.5 hours

Example 2

Meal : 1:12 insulin:CHO ratio•House salad with blue cheese dressing

•meat lasagna

•2 garlic rolls

•1/2 slice apple pie a la mode

•initial bolus: 6 units (~ 80 gm cho)

•dual wave of 3 units + 4 units over 2 hours when dessert arrives

T1DM PEARLS

• Do basal checks especially overnight

• Bolus is correct if 2 hour post-prandial is at target

• Total Daily Insulin Need: ~0.6-0.8 u/kg Total Daily Dose (TDD)

• Basal: ~ 0.3 u/kg (~ 40-50% of TDD)

• Bolus: ~ 50-60% of TDD

• Most need to lead meal bolus by 15-30 minutes

Diabetes Burnout

Adopt the pace of nature-Her secret is patience

Ralph Waldo Emerson

Management Software

• Personal –Animas, Deltec, Insulet• Web based – Animas, Medtronic Carelink,

Carelink Pro

• Helpful for review of data:– Insulin use– BG records– CHO records– Alarms– Settings

Insulin Pump Software Download

Sensor Augmented Pump

T1DM & Pregnancy

Effectiveness of Sensor-Augmented Insulin Pump Therapy in Type 1 Diabetes

Bergenstal RM, Tamborlane WV, Ahmann A, et al. N Engl J Med. doi:10.1056/NEJMoa1002853.

STAR 3 Summary

Conclusions:• The decrease in A1C levels in the SAP group was

achieved at 3 months and sustained throughout the 1 year study.

• The improvement in A1C levels was achieved without an increase in the rate of severe hypoglycemic events andwithout an increase in the time spent at an AUC <70 mg/dL.

• A significantly greater number of adults and pediatric subjects in the SAP group reached ADA age specific A1C targets.

STAR 3 Measures of Success

• Subjects with the most favorable changes in 1-year A1C values had

More in-target sensor glucose values

More Bolus Wizard interactions

More sensor use

Lower glycemic variability

Used smaller boluses per kg (0.06 vs. 0.07)

• Total daily insulin dosage, TDD/kg, and bolus-to-basal ratios did not correlate with changes in A1C

Pump Checklist

• Will need a “back up” regimen

• Pump Holiday

• Travel issues

• Record pump settings

The Closed Loop 2011(As Good as it Gets )