INTENSIVE INSULIN THERAPY

1
INTENSIVE INSULIN THERAPY

• J. Robin Conway M.D.
• Diabetes Clinic, Smiths Falls, ON
• 1-800-717-0145

2
Objectives

• Optimize diabetes management
• Assist you in initiating insulin in your office
• When to start insulin therapy?
• Insulins, doses, delivery options
• Patient training

3
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

4
Type 1 Diabetes

• Impaired or absent ß cell function
• ? insulin secretion
• Normal insulin action
• ? insulin sensitivity
• The insulin deficiency results in unacceptable
  blood glucose control

5
Type 2 Diabetes Double Impairment

• Impaired ß 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 diabetes
• Maintaining HbA1C level lt 7
• Achieving HbA1C lt 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)
(lt 0.07)
Preprandial
3.5-6.1
4-7
glycemia
(mmol/L)
Postprandial
glycemia
4.4-7.8
7-11
(
mmol/L)
Haars s et al., CMAJ 2003 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 of
  hypoglycemia
• B.Proper training and correct use of glucose
  monitor
• C.Target desired glycemic levels for each patient

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A. Hypoglycemia

• Definition Glycemia lt 3.8 mmol
• Patients may experience hypoglycemia at different
  glycemic levels

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Symptoms of Hypoglycemia

• Mild
• lt 3.3 mmol/L
• Neurovegetative symptoms
• Sweating
• Trembling
• Palpitations
• Anxiety
• Tingling
• Pallor
• Hunger

• Moderate to Severe
• lt 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 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

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Hypoglycemia Treatment Guidelines

• The Rule of 15
• If BG is 4 mmol/L or below
• Treat with 15 grams of carbohydrates (glucose
  tabs)
• Check BG in 15 minutes, and if not above 4
  mmol/L, repeat treatment
• Glucagon
• Current emergency kit readily available and
  knowledgeable person trained to administer

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PreventingHyperglycemia and DKA

• Monitor BG 4-6 times per day
• Use Correction Boluses when appropriate

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Hyperglycemia Treatment GuidelinesThe Key to
Preventing DKA

• 1st BG over 14 mmol/L
• Take a correction bolus, check again in 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 is
  IDEAL 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 severe
  hyperglycemia
• To adjust treatment to the circumstances of daily
  life using an insulin scale prescribed by the
  attending 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 2
• 3-8 readings/day
• Important to stress the need to vary testing
  times
• AC, PC, h.s. and prn during the night
  

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Injection Tools and Options

• Durable delivery devices
• Novolin-Pen 3
• Novolin-Pen Junior
• InDuo
• Innovo
• HumaPen
• Insulin pumps
• Syringes

• Disposable multidose, prefilled (3.0 mL)
• NovolinSet (NPH, Toronto, 30/70 )
• Humulin N

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Advancing Insulin Therapy Through Device
Innovation
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Goal of Insulin Therapy
We are trying to duplicate how the pancreas works
in releasing insulin for someone who doesnt have
diabetes
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Non-diabetic Insulin and Glucose Profiles
Breakfast
Lunch
Supper
75
Insulin
50
Insulin (µU/mL)
25
Basal insulin
0
9.0
Glucose
6.0
Glucose (mmo/L)
3.0
Basal glucose
0
7
8
9
10
11
12
1
2
3
4
5
6
7
8
9
a.m.
p.m.
Time of Day
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Insulin Preparations
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Insulin PreMixes

• Regular intermediate
• Novolin 10/90, 20/80, 30/70, 40/60, 50/50
• Humulin 30/70, 20/80
• Analogue Pre-Mix
• Humalog 25/75 (insulin lispro protamine
  suspension)
• 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
Blood Glucose (mmols)
10- 8- 6- 4- 2- 0

8am noon 6pm
2am 4am
8am
Time
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Blood Glucose (mmols)
10- 8- 6- 4- 2-
0
Two injections/day
R or H N in AM
R or H N at Supper
8am noon 6pm
2am 4am
8am
Time
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Blood Glucose (mmols)
10- 8- 6- 4- 2-
0
Three injections/day
R or H N in AM
R or H at Supper
N before bed
8am noon 6pm
2am 4am
8am
Time
30
Blood Glucose (mmols)
Four injections/day
10- 8- 6- 4- 2-
0
R or H at every meal
N or U once or twice/day
8am noon 6pm
2am 4am
8am
Time
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Blood Glucose (mmols)
Continuous Infusion
10- 8- 6- 4- 2-
0
8am noon 6pm
2am 4am
8am
Time
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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 postprandial hypoglycaemia
  (4-6 hours)
• Need for additional snack

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Adherence to Injection Recommendation (Canada)
"When do you inject your insulin?"
100
42
of Respondents
32
22
4
0
1998 Roper Starch Canada, Premix Insulin Using
Respondents.
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Dissociation of Regular Human Insulin
Regular Human Insulin
peak time2-4 hr
10-3 M
10-3 M
10-5 M
10-8 M
Û
Û
Û
formulation
hexamers
dimers
monomers
capillary membrane
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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
Breakfast
Lunch
Supper
75
Insulin
50
Insulin (µU/mL)
25
Basal insulin
0
9.0
Glucose
6.0
Glucose (mmo/L)
3.0
Basal glucose
0
7
8
9
10
11
12
1
2
3
4
5
6
7
8
9
a.m.
p.m.
Time of Day
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NovoRapid (insulin aspart)

• Time-Action Profile

NovoRapid Rapid-acting insulin analogue
Onset 10-20 minutes Maximum effect 1-3
hours Duration 3-5 hours
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Goal of Insulin Therapy
We are trying to duplicate how the pancreas works
in releasing insulin for someone who doesnt have
diabetes
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Insulin Therapy Options

• MDI therapy
• 0.5 units/kg total daily dose
• 4x/day 40 NPH _at_ hs and 60 rapid acting
  analogue ac meals
• For patients with significant complications (i.e.
  renal failure, foot infections, CVD, etc)

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Basal Insulin
In someone without diabetes, the pancreas
delivers a small amount of insulin continuously
to cover the bodys non-food related insulin
needs.
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Bolus Insulin
The amount of insulin required to cover the food
you eat.
Fast-acting or Short-acting (clear) insulin works
as a 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 is needed 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 or next
  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 action
  corresponds to most abnormal value (pre-meal)
• If all values are abnormal - start with fasting
  glycemia 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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Full Range of Novo Nordisk Insulins
NovoRapid Penfill Rapid-acting human insulin
analogue (insulin aspart)
Onset 10-20 minutes Maximum effect 1-3
hours Duration 3-5 hours
Novolinge Toronto Penfill Short-acting
insulin (insulin injection, human biosynthetic)
Onset 0.5 hour Maximum effect 1-3
hours Duration 8 hours
Novolinge NPH Penfill Intermediate-acting
Insulin (insulin injection, human biosynthetic)
Onset 1.5 hours Maximum effect 4-12
hours Duration 24 hours
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Somogyi Effect

• Hyperglycemia secondary to asymptomatic
  hypoglycemia (especially at night)
• If the insulin is increased in evening, the
  problem worsens
• Check capillary glycemia around 3 a.m. to
  eliminate 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 hyperglycemia guidelines

• 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
• HbA1C is 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?