Intensive Insulin Therapy

www.diabetesclinic.
ca
1
INTENSIVE INSULIN
THERAPY
J. Robin Conway M.D.
Diabetes Clinic, Smiths Falls, ON
1-800-717-0145

www.diabetesclinic.ca
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 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 cell function:
insulin secretion
Impaired insulin action:
insulin resistance
Results in unacceptable blood glucose
control

6
Type 1 & 2 Diabetes: Key Concepts
Minimizing the complications of diabetes
requires:
Early diagnosis and treatment of diabetes
Maintaining HbA
1C
level < 7%
Achieving HbA
1C
< 7% requires control of
post-prandial and fasting hyperglycemia
7
CDA Guidelines (for glycemic control)
Normal Optimal
A
1C
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., 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.
8
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
9
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

10
A. Hypoglycemia
Definition: Glycemia < 3.8 mmol
Patients may experience hypoglycemia at
different glycemic levels

11
Symptoms of Hypoglycemia
Mild
< 3.3 mmol/L
Neurovegetative
symptoms
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
12
Preventing Hypoglycemia
Check BG 4-6 times per day
Carry glucose tablets
Have Glucagon Kit available
13
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
14
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
15
Preventing
Hyperglycemia and DKA
Monitor BG 4-6 times per day
Use Correction Boluses when appropriate
16
Hyperglycemia Treatment Guidelines
The 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
17
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

18
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

19
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
20
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
21
Advancing Insulin Therapy Through
Device Innovation

22
We are trying to duplicate
how the pancreas works in
releasing insulin for
someone who doesnt
have diabetes
Goal of Insulin Therapy
23
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
24
Insulin Preparations
Start 3-4
hrs.
Peakless
Humulin
U vial only
Lantus (Glargine) vial only
Levemir (Detemir) cartridge
Prolonged
action
Start 1.5
hrs
Peak 7 hr

Novolin
ge NPH
Humulin
N

Intermediate
Vial and cartridge

Start 30-60
min.
Peak 4 hr
Novolin
ge Toronto
Humulin
R
Short-acting
(regular)
Vial and cartridge
Start < 15
min.

Aspart (NovoRapid
)
Lispro (Humalog
)
Rapid-acting
Vial and cartridge
25
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
26
Normal Blood Glucose Levels
Blood Glucose (mmols)
10-
8-
6-
4-
2-
0

8am noon 6pm 2am 4am 8am
Time
27
Normal Blood Glucose Levels
10-
8-
6-
4-
2-
0

Time
28
Two injections/day
Time
R or H + N in AM R or H + N at Supper
10-
8-
6-
4-
2-
0

29
Three injections/day
Time
R or H + N in
AM
R or H at
Supper
N before bed
10-
8-
6-
4-
2-
0

30
Four injections/day
Time
R or H at every meal N or U once or twice/day
10-
8-
6-
4-
2-
0

31
Continuous Infusion
Time
10-
8-
6-
4-
2-
0

32
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
33
Adherence to Injection Recommendation
(Canada)
4%
42%
32%
22%
0
100
3045 min
1530 min 015 min 015 min
%

o
f

R
e
s
p
o
n
d
e
n
t
s

B e f o r e
Meal
After
"When do you inject your insulin?"
1998 Roper Starch Canada, Premix Insulin Using
Respondents.
34
Dissociation of Regular Human
Insulin
Regular 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
35
Objectives for the Development of Short-
Acting Insulin Analogues
Modify time action to address
Postprandial hyperglycemia
Hypoglycemia

Improve safety and convenience
36
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
37
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
38
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
39
We are trying to duplicate
how the pancreas works in
releasing insulin for
someone who doesnt
have diabetes
Goal of Insulin Therapy
40
Insulin Therapy Options
MDI therapy
0.5 units/kg = total daily dose
4x/day 40% NPH @ hs and 60% rapid acting
analogue ac meals
For patients with significant complications (i.e.
renal failure, foot infections, CVD, etc)
41
In someone without diabetes, the
pancreas delivers a small amount of
insulin continuously to cover the bodys
non-food related insulin needs.
Basal Insulin
42
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
43
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
44
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
45
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
46
Novolin
ge 30/70
Time-Action Profile
Premixed insulin
Onset: 0.5 hour
Duration: 24 hours
47
30/70 - Twice/day
48
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

49
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
50
NovoRapid
Penfill

Rapid-acting human
insulin analogue
(insulin aspart)
Novolin
ge Toronto Penfill

Short-acting insulin
(insulin injection, human biosynthetic)
Novolin
ge NPH Penfill

Intermediate-acting
Insulin (insulin injection, human
biosynthetic)
0 2 4 6 8 10 12 14 16 18 20 22 24
Onset: 10-20 minutes
Duration: 3-5 hours
Onset: 0.5 hour
Duration: 8 hours
Onset: 1.5 hours
Duration: 24 hours
Full Range of Novo Nordisk Insulins
51
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
52
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
53
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
HbA
1C
is 9.5 %, FBS 11.8

What is the next step?

54
Case Study #2
Patient K.G., DM for 15 years
BMI = 23
Meds: Metformin 1000 mg BID and Gluconorm 2
mg TID
HbA
1C
= 8.5%, FBS 7.4
Post MI

What is the next step?

Intensive Insulin Therapy

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www.diabetesclinic.

10/90, 20/80, 30/70, 40/60, 50/50

25/75 (insulin lispro protamine

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