www.diabetesclinic.ca 1 intensive insulin therapy j. robin conway m.d. diabetes clinic, smiths...
TRANSCRIPT
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www.diabetesclinic.ca 1
INTENSIVE INSULIN THERAPY
J. Robin Conway M.D.
Diabetes Clinic, Smiths Falls, ON
1-800-717-0145
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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 attitudesPatient attitudes– Fear of needles– Insulin viewed as a threat by patient & physician– Hypoglycemia
2. Physician AttitudesPhysician Attitudes– Discomfort with insulin
• Lack of knowledge and experience
– Fear of needles
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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
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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 < 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)
Preprandialglycemia(mmol/L)
3.5-6.1 4-7
Postprandialglycemia(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.
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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 < 3.8 mmol
• Patients may experience hypoglycemia at different glycemic levels
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Symptoms of HypoglycemiaMild• < 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
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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 15The 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: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 patient’s 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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We are trying to duplicate how the pancreas works in
releasing insulin for someone who doesn’t
have diabetes
Goal of Insulin Therapy
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Non-diabetic Insulin and Glucose Profiles
9.0
6.0
3.0
07 8 9 101112 1 2 3 4 5 6 7 8 9
Insulin
Glucose
a.m. p.m.
Breakfast Lunch Supper75
50
25
0 Basal insulin
Basal glucose
Insulin(µU/mL)
Glucose(mmo/L)
Time of Day
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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
IntermediateVial 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-actingVial and cartridge
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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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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 postprandial hypoglycaemia (4-6 hours)– Need for additional snack
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Adherence to Injection Recommendation Adherence to Injection Recommendation (Canada)(Canada)
4%
42%32%
22%
0
100
30–45 min 15–30 min 0–15 min 0–15 min
% o
f R
es
po
nd
ents
B e f o r e Meal After
"When do you inject your insulin?"
1998 Roper Starch Canada, Premix Insulin Using Respondents.
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Dissociation of Regular Human Insulin
Regular Human Insulin
10-3 M 10-3 M 10-5 M 10-8 M peak time2-4 hr
formulation
capillary membrane
hexamers dimers monomers
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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
07 8 9 101112 1 2 3 4 5 6 7 8 9
Insulin
Glucose
a.m. p.m.
Breakfast Lunch Supper75
50
25
0 Basal insulin
Basal glucose
Insulin(µU/mL)
Glucose(mmo/L)
Time of Day
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NovoRapid® (insulin aspart)
Time-Action Profile0 2 4 6 8 10 12 14 16 18 20 22 24
Onset: 10-20 minutesMaximum effect: 1-3 hoursDuration: 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 doesn’t
have diabetes
Goal of Insulin Therapy
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Insulin Therapy Options
• MDI therapyMDI 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…)
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In someone without diabetes, the pancreas delivers a small amount of
insulin continuously to cover the body’s
non-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 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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Novolin®ge 30/70
Time-Action Profile
Premixed insulin
Onset: 0.5 hourMaximum effect: 2-12 hoursDuration: 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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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)
00 22 44 66 88 1010 1212 1414 1616 1818 2020 2222 2424
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 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 Patient’s Role
Every DayEvery Day• Check BG 4-6 times a day,
and always before bed• Follow hypoglycemia
guidelines• Follow hyperglycemia
guidelines
Every 3 monthsEvery 3 months• Visit healthcare provider -
even if feeling well
• Review log book and pump settings with physician
• Get an A1c test
Every monthEvery 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?