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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

www.diabetesclinic.ca 2
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

www.diabetesclinic.ca 3
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

www.diabetesclinic.ca 4
Type 2 Diabetes: Double Impairment
• Impaired ß cell function:
↓ insulin secretion
• Impaired insulin action:
↑ insulin resistance
• Results in unacceptable blood glucose
control

www.diabetesclinic.ca 5
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

www.diabetesclinic.ca 6
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.
www.diabetesclinic.ca 7
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

www.diabetesclinic.ca 8
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

www.diabetesclinic.ca 9
A. Hypoglycemia
• Definition: Glycemia < 3.8 mmol
• Patients may experience hypoglycemia at
different glycemic levels

www.diabetesclinic.ca 10
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

www.diabetesclinic.ca 11
Preventing Hypoglycemia
• Check BG 4-6 times per day

• Carry glucose tablets

• Have Glucagon Kit available

www.diabetesclinic.ca 12
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
www.diabetesclinic.ca 13
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
www.diabetesclinic.ca 14
Preventing
Hyperglycemia and DKA

• Monitor BG 4-6 times per day

• Use Correction Boluses when appropriate

www.diabetesclinic.ca 15
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

www.diabetesclinic.ca 16
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

www.diabetesclinic.ca 17
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

www.diabetesclinic.ca 18
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

www.diabetesclinic.ca 19
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

www.diabetesclinic.ca 20
Advancing Insulin Therapy Through
Device Innovation

www.diabetesclinic.ca 21
Goal of Insulin Therapy
We are trying to duplicate
how the pancreas works in
releasing insulin for
someone who doesn’t
have diabetes

www.diabetesclinic.ca 22
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 101112 1 2 3 4 5 6 7 8 9
a.m. p.m.
Time of Day
www.diabetesclinic.ca 23
Insulin Preparations
Rapid-acting Aspart (NovoRapid®) Start < 15
min.
Vial and cartridge Lispro (Humalog®)

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 hrs


Vial and cartridge Peak 7 hr
Humulin® N

Prolonged Humulin® U vial only Start 3-4


action Lantus (Glargine) vial only hrs. Peakless
Levemir www.diabetesclinic.ca
(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
www.diabetesclinic.ca 25
Normal Blood Glucose Levels

Blood Glucose (mmols)

10-

8-

6-

4-

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

Time
0
www.diabetesclinic.ca 26
Normal Blood Glucose Levels

Blood Glucose (mmols)

10-

8-

6-

4-

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

Time
0
www.diabetesclinic.ca 27
Blood Glucose (mmols)

10- Two injections/day

8- R or H + N in AM R or H + N at Supper
6-

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

Time
2-
www.diabetesclinic.ca 28
Blood Glucose (mmols)

10- Three injections/day

8- R or H + N in R or H at N before bed
AM Supper
6-

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

2- Time
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Blood Glucose (mmols)

10- Four injections/day

8-
R or H at every meal N or U once or twice/day
6-

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

Time
2-
www.diabetesclinic.ca 30
Blood Glucose (mmols)

10- Continuous Infusion

8-

6-

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

Time
2-
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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
www.diabetesclinic.ca 32
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


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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

www.diabetesclinic.ca 34
Objectives for the Development of Short-
Acting Insulin Analogues

• Modify time action to address


– Postprandial hyperglycemia
– Hypoglycemia

• Improve safety and convenience

www.diabetesclinic.ca 35
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

www.diabetesclinic.ca 36
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 101112 1 2 3 4 5 6 7 8 9
a.m. p.m.
Time of Day
www.diabetesclinic.ca 37
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

www.diabetesclinic.ca 38
Goal of Insulin Therapy
We are trying to duplicate
how the pancreas works in
releasing insulin for
someone who doesn’t
have diabetes

www.diabetesclinic.ca 39
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…)

www.diabetesclinic.ca 40
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.

www.diabetesclinic.ca 41
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

www.diabetesclinic.ca 42
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

www.diabetesclinic.ca 43
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

www.diabetesclinic.ca 44
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
www.diabetesclinic.ca 45
Novolin®ge 30/70
Time-Action Profile

Premixed insulin

Onset: 0.5 hour


Maximum effect: 2-12 hours
Duration: 24 hours

www.diabetesclinic.ca 46
30/70 - Twice/day

www.diabetesclinic.ca 47
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

www.diabetesclinic.ca 48
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

www.diabetesclinic.ca 49
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 Maximum effect: 1-3 hours
(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)

www.diabetesclinic.ca 50
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

www.diabetesclinic.ca 51
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
www.diabetesclinic.ca 52
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?

www.diabetesclinic.ca 53
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?

www.diabetesclinic.ca 54