Intensive Insulin Therapy

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www.diabetesclinic.ca 1

INTENSIVE INSULIN

THERAPY

J. Robin Conway M.D.

Diabetes Clinic, Smiths Falls, ON1-800-717-0145


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Objectives

Optimize diabetes management

Assist you in initiating insulin in your office

When to start insulin therapy?Insulins, doses, delivery options

Patient training


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Challenges in Initiating Insulin?

1. Patient attitudes

Fear of needles

Insulin viewed as a threat by patient & physician

Hypoglycemia

2. Physician Attitudes

Discomfort with insulin Lack of knowledge and experience

Fear of needles


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Type 1 Diabetes:

Impaired or absent cell function:

insulin secretion

Normal insulin action: insulin sensitivity

The insulin deficiency results in

unacceptable blood glucose control


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Type 2 Diabetes: Double Impairment

Impaired cell function:

insulin secretion

Impaired insulin action: insulin resistance

Results in unacceptable blood glucose

control


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Type 1 & 2 Diabetes: Key Concepts

Minimizing the complications of diabetes

requires:

Early diagnosis and treatment of diabetesMaintaining HbA1Clevel < 7%

Achieving HbA1C< 7% requires control of

post-prandial and fasting hyperglycemia


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CDA Guidelines (for glycemic control)

Normal Optimal

A1C level (0.04-0.06) (< 0.07)

Preprandial

glycemia(mmol/L)

3.5-6.1 4-7

Postprandial

glycemia( mmol/L)

4.4-7.8 7-11

Haars s et al.,CMAJ2003; 159 (Suppl.): S1-29. Gerstein, H.C. et al. CDA views on the UKPDS and revision of the

guidelines affected by the results of this study.


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Steps to Glycemic Control

Establish glycemic objectives

Target fasting and post-prandial glycemia

Diet counseling with exercise component Diabetes education for every patient

Pharmacological treatment; oral and insulin


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Patient Counselling Topics

A.Review symptoms and treatment ofhypoglycemia

B.Proper training and correct use of glucosemonitor

C.Target desired glycemic levels for each

patient


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A. Hypoglycemia

Definition: Glycemia < 3.8 mmol

Patients may experience hypoglycemia at

different glycemic levels


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Symptoms of Hypoglycemia

Mild < 3.3 mmol/L

Neurovegetativesymptoms

Sweating Trembling

Palpitations

Anxiety

Tingling

Pallor Hunger

Moderate to Severe

< 2.8 mmol/L

Symptoms of glucopenia

Confusion

Visual disturbances Weakness

Speech disorder

Behavioural disorder

Drowsiness

Coma

Convulsions


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Preventing Hypoglycemia

Check BG 4-6 times per day

Carry glucose tablets

Have Glucagon Kit available


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Preventing Hypoglycemia

Test before driving and ideally 1 hour later(target: over 5.5 mmol/L)

Perform two SMBG 30 minutes apart prior tobedtime (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


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Hypoglycemia Treatment

GuidelinesThe Rule of 15 If BG is 4 mmol/L or below

Treat with 15 grams of carbohydrates (glucosetabs)

Check BG in 15 minutes, and if not above 4mmol/L, repeat treatment

Glucagon Current emergency kit readily available and

knowledgeable person trained to administer


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Preventing

Hyperglycemia and DKA

Monitor BG 4-6 times per day

Use Correction Boluses when appropriate


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Hyperglycemia Treatment Guidelines

The Key to Preventing DKA

1st BG over 14 mmol/L:

Take a correction bolus, check againin 1 hour

Call physician immediately or go to ER if

nausea and vomiting are present


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B. Patient Training

Training by a multidisciplinary team at DEC isIDEAL for:

Diet counseling

Education on the injection sites Education on the various injection devices

Evaluation of the patients support network

Other resources may exist for training, i.e. retail

pharmacy


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C. Blood Glucose Monitoring

To adjust the insulin treatment

To detect or confirm hypoglycemia or severehyperglycemia

To adjust treatment to the circumstances of dailylife using an insulin scale prescribed by theattending physician

To improve patient safety and increase motivation

to comply with treatment


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Ideal Testing Frequency

Stable type 2

1-2 readings/day

Type 1 or Unstable type 23-8 readings/day

Important to stress the need to vary testing

timesAC, PC, h.s. and prn during the night


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Injection Tools and Options

Durable delivery devices

Novolin-Pen3

Novolin-PenJunior

InDuo

Innovo

HumaPen

Insulin pumps

Syringes

Disposable: multidose,prefilled (3.0 mL)

NovolinSet (NPH,Toronto, 30/70 )

HumulinN


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Advancing Insulin Therapy Through

Device Innovation


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We are trying to duplicate

how the pancreas works in

releasing insulin for

someone who doesnt

have diabetes

Goal of Insulin Therapy


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Non-diabetic Insulin and Glucose

Profiles

9.0

6.0

3.0

0

7 8 9 10 11 12 1 2 3 4 5 6 7 8 9

Insulin

Glucose

a.m. p.m.

Breakfast Lunch Supper

75

50

25

0 Basal insulin

Basal glucose

Insulin

(U/mL)

Glucose

(mmo/L)

Time of Day

Insulin Preparations


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Insulin Preparations

Start 3-4

hrs.

Peakless

HumulinU vial onlyLantus (Glargine) vial only

Levemir (Detemir) cartridge

Prolonged

action

Start 1.5

hrs

Peak 7 hr

Novolinge NPH

HumulinN

IntermediateVial and cartridge

Start 30-60

min.

Peak 4 hr

Novolinge Toronto

HumulinR

Short-acting

(regular)

Vial and cartridge

Start < 15

min.Aspart (NovoRapid)

Lispro (Humalog)

Rapid-actingVial and cartridge


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Insulin PreMixes

Regular + intermediate

Novolin10/90, 20/80, 30/70, 40/60, 50/50

Humulin30/70, 20/80 Analogue Pre-Mix

Humalog25/75 (insulin lispro protaminesuspension)

NovoMix 30* (protaminated insulin aspart)

* Not available


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Normal Blood Glucose Levels

Blood Glucose (mmols)

10-

8-

6-

4-

2-

0

8am noon 6pm 2am 4am 8am

Time


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Normal Blood Glucose Levels


10-

8-

6-

4-

2-

0


Time


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Two injections/day



Time

R or H + N in AM

R or H + N at Supper

10-

8-

6-

4-

2-

0


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Three injections/day



Time

R or H + N in

AM

R or H at

Supper

N before bed

10-

8-

6-

4-

2-

0


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Four injections/day



Time

R or H at every meal N or U once or twice/day

10-

8-

6-

4-

2-

0


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Continuous Infusion



Time

10-

8-

6-

4-

2-

0


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Limitations of Regular Human

Insulin

Slow onset of activity

Should be given 30 to 45 minutes before meal

Inconvenient for patients Long duration of activity

Lasts up to 12 hours

Potential for late postprandialhypoglycaemia (4-6 hours)

Need for additional snack


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Adherence to Injection Recommendation

(Canada)

4%

42%32%

22%

0

100

3045 min 1530 min 015 min 015 min

%o

fRespo

ndents

B e f o r e Meal After

"When do you inject your insulin?"

1998 Roper Starch Canada, Premix Insulin Using


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www.diabetesclinic.ca34

Dissociation of Regular Human

InsulinRegular Human Insulin

10

-3

M 10

-3

M 10

-5

M 10

-8

M

peak time

2-4 hr

formulation

capillary membrane

hexamers dimers monomers

Objectives for the Development of Short


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Objectives for the Development of Short-

Acting Insulin Analogues

Modify time action to address

Postprandial hyperglycemia

Hypoglycemia

Improve safety and convenience


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Whats new in type 1 diabetes

treatment? Insulin analogues.

Physiological insulin replacement

Aggressive intensive management

4 injections per day

Insulin infusion pumps

Continuous glucose monitoring systems

Integrated technologies for monitoring control


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Non-diabetic Insulin and Glucose

Profiles

9.0

6.0

3.0

0

7 8 9 10 11 12 1 2 3 4 5 6 7 8 9

Insulin

Glucose

a.m. p.m.

Breakfast Lunch Supper

75

50

25

0 Basal insulin

Basal glucose

Insulin

(U/mL)

Glucose

(mmo/L)

Time of Day


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NovoRapid(insulin aspart)

Time-Action Profile

0 2 4 6 8 10 12 14 16 18 20 22 24

Onset: 10-20 minutes

Maximum effect: 1-3 hours

Duration: 3-5 hours

NovoRapid

Rapid-acting insulin analogue


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We are trying to duplicate

how the pancreas works in

releasing insulin for

someone who doesnt

have diabetes

Goal of Insulin Therapy


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Insulin Therapy Options

MDI therapy

0.5 units/kg = total daily dose

4x/day 40% NPH @ hs and 60% rapid actinganalogue ac meals

For patients with significant complications (i.e.

renal failure, foot infections, CVD, etc)


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In someone without diabetes, the

pancreas delivers a small amount of

insulin continuously to cover the bodysnon-food related insulin needs.

Basal Insulin


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The amount of insulin required to

cover the food you eat.

Fast-acting or Short-acting

(clear) insulin works as a

Bolus Insulin

Bolus Insulin


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Why count carbs?

More precise way of measuring the

impact of a meal on blood sugar

Lets you decide how much insulin isneeded to cover the meal

Greater flexibility -eat what you want,

when you want to eat it


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Fine Tuning: Bolus Doses

Carbohydrate counting or pre-determined

meal portion

Individualized insulin to carbohydrate dose

or insulin to meal dose

Adjust bolus based on post-meal BGs ornext pre-meal BG


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Fine Tuning: Basal Rate

Monitor BG pre-meal, post-meal,

bedtime, 12am, and 2-4am

Test fasting BG with skipped meals

Adjust nighttime basal based on

2-4am and pre-breakfast BG

Adjust basal by 0.1 u/hr to avoid

over-correction


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Novolinge 30/70

Time-Action Profile

Premixed insulin

Onset: 0.5 hour

Maximum effect: 2-12 hours

Duration: 24 hours


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30/70 - Twice/day


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30/70 Dose Calculation

Weight = 80 kg

80 kg x 0.3 U/kg = 24 U

2/3 in the AM = 16 Units

1/3 at supper = 8 Units


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Dosage Changes

Change insulin dose so that peak of actioncorresponds to most abnormal value (pre-meal)

If all values are abnormal - start with fastingglycemia followed by lunch, supper and bedtime

Change the dose by increments of 1-4 U

Not more than twice/week

Monitor for PATTERNS in hypoglycemia


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NovoRapidPenfillRapid-acting humaninsulin analogue(insulin aspart)

Novolinge Toronto PenfillShort-acting insulin(insulin injection, human biosynthetic)

Novolinge NPH PenfillIntermediate-actingInsulin (insulin injection, human

biosynthetic)

0 2 4 6 8 10 12 14 16 18 20 22 24

Onset: 10-20 minutesMaximum effect: 1-3 hoursDuration: 3-5 hours

Onset: 0.5 hourMaximum effect: 1-3 hoursDuration: 8 hours

Onset: 1.5 hoursMaximum effect: 4-12 hoursDuration: 24 hours

Full Range of Novo Nordisk Insulins


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Somogyi Effect

Hyperglycemia secondary to asymptomatichypoglycemia (especially at night)

If the insulin is increased in evening, theproblem worsens

Check capillary glycemia around 3 a.m. toeliminate hypoglycemia

In this case, reduce the h.s. NPH


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Follow-Up: The Patients Role

Every Day

Check BG 4-6 times a day,and always before bed

Follow hypoglycemia

guidelines Follow hyperglycemiaguidelines

Every 3 months

Visit healthcare provider -

even if feeling well

Review log book and pump

settings with physician Get an A1c test

Every month

Review DKA prevention Check BG

- 3am (overnight)

- 1 and/or 2-hour post-meal BG for all meals on a given day


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Case Study #1

Patient R.M., DM for 9 years

BMI = 34,

Meds: metformin 1000 mg BID and

glyburide 10 mg BID, Avandia 8 mg OD HbA1Cis 9.5 %, FBS 11.8

What is the next step?


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Case Study #2

Patient K.G., DM for 15 years

BMI = 23

Meds: Metformin 1000 mg BID and Gluconorm 2

mg TID HbA1C= 8.5%, FBS 7.4

Post MI

What is the next step?

Documents

Intensive Insulin Therapy