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

www.diabetesclinic.ca 1

INTENSIVE INSULIN THERAPY

J. Robin Conway M.D.

Diabetes Clinic, Smiths Falls, ON

1-800-717-0145


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 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


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)

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.


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 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


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 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


PreventingHyperglycemia and DKA

• Monitor BG 4-6 times per day

• Use Correction Boluses when appropriate


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


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– 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


Advancing Insulin Therapy Through Device Innovation


We are trying to duplicate how the pancreas works in

releasing insulin for someone who doesn’t

have diabetes

Goal of Insulin Therapy


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


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


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-

0

8am noon 6pm 2am 4am 8am

Time


Normal Blood Glucose Levels


10-

8-

6-

4-

2-

0


Time


Two injections/day



Time

R or H + N in AM R or H + N at Supper

10-

8-

6-

4-

2-

0


Three injections/day



Time

R or H + N in AM

R or H at Supper

N before bed

10-

8-

6-

4-

2-

0


Four injections/day



Time

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

10-

8-

6-

4-

2-

0


Continuous Infusion



Time

10-

8-

6-

4-

2-

0


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 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.


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


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

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


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


We are trying to duplicate how the pancreas works in

releasing insulin for someone who doesn’t

have diabetes

Goal of Insulin Therapy


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…)


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


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


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 hourMaximum effect: 2-12 hoursDuration: 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


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


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 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


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?

Documents

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