Roller Coaster of Insulin Therapy Rationale for insulin therapy in type 2 diabetes
Intensive Insulin Therapy
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Transcript of 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
Blood Glucose (mmols)
10-
8-
6-
4-
2-
0
8am noon 6pm 2am 4am 8am
Time
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Two injections/day
Blood Glucose (mmols)
8am noon 6pm 2am 4am 8am
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
Blood Glucose (mmols)
8am noon 6pm 2am 4am 8am
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
Blood Glucose (mmols)
8am noon 6pm 2am 4am 8am
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
Blood Glucose (mmols)
8am noon 6pm 2am 4am 8am
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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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?