Intensive Insulin Therapy

INTENSIVE INSULIN
THERAPY
J. Robin Conway M.D.
Diabetes Clinic, Smiths Falls, ON
1-800-717-0145
www.diabetesclinic.ca 1
Objectives
• Optimize diabetes management
• Assist you in initiating insulin in your office
– When to start insulin therapy?
– Insulins, doses, delivery options
– Patient training
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
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
Type 2 Diabetes: Double Impairment
• Impaired ß cell function:
  insulin secretion
• Impaired insulin action:
  insulin resistance
• Results in unacceptable blood glucose
control
Type 1 & 2 Diabetes: Key Concepts
• Minimizing the complications of diabetes
requires:
– Early diagnosis and treatment of diabetes
– Maintaining HbA1C level < 7%
• Achieving HbA1C < 7% requires control of
post-prandial and fasting hyperglycemia
CDA Guidelines (for glycemic control)
Normal Optimal
A1C level (0.04-0.06) (< 0.07)

Preprandial
glycemia 3.5-6.1 4-7
(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.
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
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
A. Hypoglycemia
• Definition: Glycemia < 3.8 mmol
• Patients may experience hypoglycemia at
different glycemic levels
Symptoms of Hypoglycemia
Mild Moderate to Severe
• < 3.3 mmol/L • < 2.8 mmol/L
• Neurovegetative • Symptoms of glucopenia
symptoms – Confusion
– Sweating – Visual disturbances
– Trembling – Weakness
– Palpitations – Speech disorder
– Anxiety – Behavioural disorder
– Tingling – Drowsiness
– Pallor – Coma
– Hunger – Convulsions
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 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
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
Preventing
Hyperglycemia and DKA
• Monitor BG 4-6 times per day
• Use Correction Boluses when appropriate
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
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 patient’s support network
• Other resources may exist for training, i.e. retail
pharmacy
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
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
Injection Tools and Options
• Durable delivery devices • Disposable: multidose,
– Novolin-Pen® 3 prefilled (3.0 mL)
– Novolin-Pen® Junior – NovolinSet® (NPH,
– InDuo® Toronto, 30/70 )
– Innovo® – Humulin® N
– HumaPen®
• Insulin pumps
• Syringes
Advancing Insulin Therapy Through
Device Innovation
Goal of Insulin Therapy
We are trying to duplicate
how the pancreas works in
releasing insulin for
someone who doesn’t
have diabetes
Non-diabetic Insulin and Glucose
Profiles
Breakfast Lunch Supper
75
Insulin
Insulin 50
(µU/mL)
25
0 Basal insulin
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
Insulin Preparations
Rapid-acting Aspart (NovoRapid®) Start < 15
Vial and cartridge Lispro (Humalog®) min.
Short-acting Novolin®ge Toronto Start 30-60

(regular) Humulin® R min.
Vial and cartridge Peak 4 hr
Intermediate Novolin®ge NPH Start 1.5

Vial and cartridge
Humulin® N hrs
Peak 7 hr
Prolonged Humulin® U vial only Start 3-4

action Lantus (Glargine) vial only hrs. Peakless
www.diabetesclinic.ca
Levemir (Detemir) cartridge 24
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
Normal Blood Glucose Levels
Blood Glucose (mmols)
10-
8-
6-
4-
2- 8am noon 6pm 2am 4am 8am
Time
0
Normal Blood Glucose Levels
10-
8-
6-
4-
Time
0
10- Two injections/day
8- R or H + N in AM R or H + N at Supper
6-
2-
Time
10- Three injections/day
8- R or H + N in R or H at N before bed
AM Supper
6-
2- Time
10- Four injections/day
8-
R or H at every meal N or U once or twice/day
6-
Time
2-
10- Continuous Infusion
8-
6-
2-
Time
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
Adherence to Injection Recommendation
(Canada)
"When do you inject your insulin?"
100
% of Respondents
42%
32%
22%
4%
0
30–45 min 15–30 min 0–15 min 0–15 min
Before Meal After

1998 Roper Starch Canada, Premix Insulin Using
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 hexamers dimers monomers
capillary membrane
Objectives for the Development of Short-
Acting Insulin Analogues
• Modify time action to address

– Postprandial hyperglycemia
– Hypoglycemia
• Improve safety and convenience
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
Non-diabetic Insulin and Glucose
Profiles
Breakfast Lunch Supper
75
Insulin
Insulin 50
(µU/mL)
25
0 Basal insulin
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
NovoRapid® (insulin aspart)
Time-Action Profile
0 2 4 6 8 10 12 14 16 18 20 22 24
NovoRapid®
Rapid-acting insulin analogue
Onset: 10-20 minutes

Maximum effect: 1-3 hours
Duration: 3-5 hours
Goal of Insulin Therapy
We are trying to duplicate
how the pancreas works in
releasing insulin for
someone who doesn’t
have diabetes
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…)
Basal Insulin
In someone without diabetes, the
pancreas delivers a small amount of
insulin continuously to cover the body’s
non-food related insulin needs.
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
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
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
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
Novolin®ge 30/70
Time-Action Profile
Premixed insulin
Onset: 0.5 hour

Duration: 24 hours
30/70 - Twice/day
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
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
Full Range of Novo Nordisk Insulins
0 2 4 6 8 10 12 14 16 18 20 22 24
NovoRapid® Penfill® Onset: 10-20 minutes

Rapid-acting human
insulin analogue Maximum effect: 1-3 hours
Duration: 3-5 hours
(insulin aspart)
Novolin®ge Toronto Penfill® Onset: 0.5 hour

Short-acting insulin
(insulin injection, human biosynthetic) Duration: 8 hours
Novolin®ge NPH Penfill® Onset: 1.5 hours

Intermediate-acting
Insulin (insulin injection, human Maximum effect: 4-12 hours
Duration: 24 hours
biosynthetic)
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
Follow-Up: The Patient’s Role
Every Day Every 3 months
• Check BG 4-6 times a day, and • Visit healthcare provider -
always before bed
even if feeling well
• Follow hypoglycemia
guidelines • Review log book and pump
• Follow hyperglycemia settings with physician
guidelines • 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
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?
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?

Intensive Insulin Therapy

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INTENSIVE INSULIN

A1C level (0.04-0.06) (< 0.07)

A.Review symptoms and treatment of

• Carry glucose tablets

• Have Glucagon Kit available

• Monitor BG 4-6 times per day

• Use Correction Boluses when appropriate

1st BG over 14 mmol/L:

Short-acting Novolin®ge Toronto Start 30-60

Intermediate Novolin®ge NPH Start 1.5

Prolonged Humulin® U vial only Start 3-4

Blood Glucose (mmols)

2- 8am noon 6pm 2am 4am 8am

Blood Glucose (mmols)

2- 8am noon 6pm 2am 4am 8am

10- Two injections/day

4- 8am noon 6pm 2am 4am 8am

10- Three injections/day

4- 8am noon 6pm 2am 4am 8am

10- Four injections/day

4- 8am noon 6pm 2am 4am 8am

10- Continuous Infusion

4- 8am noon 6pm 2am 4am 8am

Before Meal After

10-3 M 10-3 M 10-5 M 10-8 M peak time

formulation hexamers dimers monomers

• Modify time action to address

• Improve safety and convenience

Onset: 10-20 minutes

non-food related insulin needs.

The amount of insulin required to

• Individualized insulin to carbohydrate dose

• Adjust bolus based on post-meal BGs or

Onset: 0.5 hour

NovoRapid® Penfill® Onset: 10-20 minutes

Novolin®ge Toronto Penfill® Onset: 0.5 hour

Novolin®ge NPH Penfill® Onset: 1.5 hours

What is the next step?

What is the next step?

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