Ueda2016 wark shop - insulin therapy - mohamed mashahit

Insulin therapy

By

Prof .Mohamed Mashahit

Fayoum University

The breakthrough: Toronto 1921 – Banting & Best

Normal physiologic patterns of

glucose and insulin secretion in

our body

How Is Insulin Normally Secreted?

The rapid early rise of insulin secretion in

response to a meal is critical,

because

it ensures the prompt inhibition of endogenous

glucose production by the liver

disposal of the mealtime carbohydrate load, thus

limiting postprandial glucose excursions.

Types of Insulin

1. Rapid-acting

2. Short-acting

3. Intermediate-acting

4. Premixed

5. Basal L A

6. Extended long-acting

(Analogs)

(Regular)

(NPH)

(70/30)(Lantus & DETEMIR )

Basal insulins

NPH

• Humulin N (Eli Lilly)

• Insulatard (Novo)

• Insuman Basal

===========================================

AnalogsGlargine (Lantus)Lantus Solostar Pen (Sanofi Aventis)

Detemir (Levimir) by Novo

Degludec

Basal Insulins

Insulin Type Onset of

action

Peak of

action

Duration

of action

NPH Intermediate

acting1-2 hours 5-7 hours 13-18

hours

Glargine

(Lantus)

Aventis

Long

acting

1-2 hours Relatively

flat

Upto 24

hours

Detemir(Levimir)Novo

Long

acting

2-4 hours 8-12 hours 16-20

hours

The time course of action of any insulin may vary in different individuals, or at different times in

the same individual. Because of this variation, time periods indicated here should be considered

general guidelines only.

Bolous insulins

(Mealtime or prandial)Human Regular• Humulin R (Eli Lilly)

• Actrapid (Novo)

• Insuman Rapid

==========================================

Analogs• Lispro (Humolog) by Eli Lilly

• Aspart Novorapid ( Novo )

• Glulisine (Apidra) by Sanofi Aventis

Bolous insulins

(Mealtime or prandial)

Insulin Type Onset of

action

Peak of

action

Duration of

action

Human

regular

Short acting 30-60 minutes 2-4 hours 8-10 hours

Insulin

analogs

)

Rapid acting 5-15 minutes 1-2 hours 4-5 hours

The time course of action of any insulin may vary in different individuals, or at

different times in the same individual. Because of this variation, time periods

indicated here should be considered general guidelines only.

Pre mixed

70/30 (70% N,30% R)

• Humulin 70/30 (Eli Lilly)

• Mixtard 30 (Novo)

• Insuman Comb 30/70

•

===================================

Analogs

• Novomix 30 and 50 (Novo)

• Humolog Mix 25(Lilly)

• Humolog Mix 50(Lilly)

Inadequate

Non pharmacological

therapy

1oral agent2 oral

agents

3 oral

agents

Add Insulin Earlier in the Algorithm

•Severe symptoms

•Severe

hyperglycaemia

•Ketosis

•pregnancy

Proposed Algorithm of therapy for Type 2

Diabetes

First step into

Insulin therapy

Advantages of Insulin Therapy

• Oldest of the currently available medications, has the most clinical experience

• Most effective of the diabetes medications in lowering glycemia

– Can decrease any level of elevated HbA1c

– No maximum dose of insulin beyond which a therapeutic effect will not occur

• Beneficial effects on triglyceride and HDL cholesterol levels

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Disadvantages of Insulin Therapy

• Weight gain ~ 2-4 kg

– May adversely affect cardiovascular health

• Hypoglycemia

– However, rates of severe hypoglycemia in

patients with type 2 diabetes are low…

Type 1 DM: 61 events per 100 patient-years

Type 2 DM: 1-3 events per 100 patient-years

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Balancing Good Glycemic Control with

a Low Risk of Hypoglycemia…

Hypoglycemia

Glycemic control

The ADA Treatment

Algorithm for the Initiation

and Adjustment of Insulin

• If HbA1c is <7%...

– Continue regimen and check HbA1c every 3

months

• If HbA1c is ≥7%...

– Move to Step Two…

After 2-3 Months…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Initiating and Adjusting Insulin

Continue regimen; check

HbA1c every 3 months

If fasting BG in target range, check BG before lunch, dinner, and bed.

Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Recheck pre-meal BG levels and if out of range, may need to add another

injection; if HbA1c continues to be out of range, check 2-hr postprandial levels

and adjust preprandial rapid-acting insulin

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Pre-lunch BG out of range: add

rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at

breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add

rapid-acting insulin at dinner

Continue regimen; check

HbA1c every 3 months

Target range:3.89-7.22 mmol/L

(70-130 mg/dL)

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

If HbA1c ≤7%... If HbA1c 7%...

With the addition of basal insulin and titration

to target FBG levels, only about 60% of

patients with type 2 diabetes are able to achieve

A1C goals < 7%. In the remaining patients with

A1C levels above goal regardless of adequate

fasting glucose levels, postprandial blood

glucose levels are likely elevated.

Continue regimen; check

HbA1c every 3 months

If fasting BG in target range, check BG before lunch, dinner, and bed.

Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Recheck pre-meal BG levels and if out of range, may need to add another

injection; if HbA1c continues to be out of range, check 2-hr postprandial levels

and adjust preprandial rapid-acting insulin

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Pre-lunch BG out of range: add

rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at

breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add

rapid-acting insulin at dinner

Continue regimen; check

HbA1c every 3 months

Target range:3.89-7.22 mmol/L

(70-130 mg/dL)

If HbA1c ≤7%... If HbA1c 7%...

Step Two…

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

Step Two: Intensifying InsulinIf fasting blood glucose levels are in target range but

HbA1c ≥7%, check blood glucose before lunch, dinner,

and bed and add a second injection:

• If pre-lunch blood glucose is out of range,

add rapid-acting insulin at breakfast

• If pre-dinner blood glucose is out of range,

add NPH insulin at breakfast or rapid-acting insulin at

lunch

• If pre-bed blood glucose is out of range,

add rapid-acting insulin at dinner

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Making Adjustments

• Can usually begin with ~4 units and

adjust by 2 units every 3 days until blood

glucose is in range

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

When number of insulin Injections increase from 1-2………..Stop or taper of insulin secretagogues (sulfonylureas).

• If HbA1c is <7%...

– Continue regimen and check HbA1c every

3 months

• If HbA1c is ≥7%...

– Move to Step Three…

After 2-3 Months…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

Continue regimen; check

HbA1c every 3 months

If fasting BG in target range, check BG before lunch, dinner, and bed.

Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)

Recheck pre-meal BG levels and if out of range, may need to add another

injection; if HbA1c continues to be out of range, check 2-hr postprandial levels

and adjust preprandial rapid-acting insulin

If HbA1c ≤7%...

Bedtime intermediate-acting insulin, or

bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg)

Check FG and increase dose until in target range.

If HbA1c 7%...

Hypoglycemia

or FG >3.89 mmol/l (70 mg/dl):Reduce bedtime dose by ≥4 units

(or 10% if dose >60 units)

Pre-lunch BG out of range: add

rapid-acting insulin at breakfast

Pre-dinner BG out of range: add NPH insulin at

breakfast or rapid-acting insulin at lunch

Pre-bed BG out of range: add

rapid-acting insulin at dinner

Continue regimen; check

HbA1c every 3 months

Target range:3.89-7.22 mmol/L

(70-130 mg/dL)

If HbA1c ≤7%... If HbA1c 7%...

Step Three…

Step Three:

Further Intensifying Insulin

• Recheck pre-meal blood glucose and if out of

range, may need to add a third injection

• If HbA1c is still ≥ 7%

– Check 2-hr postprandial levels

– Adjust preprandial rapid-acting insulin

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

How to start pre mixed (70/30)

Insulin

For pre mixed insulins(70/30 preparations)

Step1:First calculate the total daily starting requirement

of insulin;

body weight(kg)/2

eg, For a 60kg patient,total daily dose =30 units

Step 2:Then devide this dose into 3 equal parts;

10+10+10

Step 3:Give 2 parts in the morning and 1 part in the

evening;

Morning=20U Evening=10 U

Dose titration of Pre-mixed(70/30)

preparations

You can increase or decrease the dose of

pre-mixed insulin by 10 % i.e

If the patients is using,

1-10 units…………….+/- 1 unit

11-20 units……………+/- 2 units

21-30 units……………+/- 3 units

31-40 units……………+/- 4 units…………………..

Advantages and disadvantages

of pre- mixed insulins

Advantages:Easy to administer for the

physician.

Easy to fill and inject by the

patient.

Provides both basal and bolus

coverage with fewer number of

injections.

Disadvantage:

No dose flexability

If u increase/decrease the dose of one

component ,the dose of other

component is also changed un desirably

vInsuman Rapid , Insuman Basal , Insuman Comp (30/70)

Pearls for practice

Never try to control diabetes with oral hypoglycemic drugs / insulin without first ensuring strict diet control.

Always bring fasting sugar to normal before trying to control post prandial / random blood sugar.

Control any underlying infection/stressful condition vigorously.

Keep meal timings regular with 6 hrs between the three meals.

Do not inject NPH before 11 p.m. Keep number of calories during the meals same from day to

day. The quantity and quality of diet should be same at same timings.

Do not use sliding scale to calculate the dose of insulin. Use proper technique to inject s/c insulin. Ensure proper storage of insulin.

Key Take-Home Messages

• Insulin is the oldest, most studied, and most effective

antihyperglycemic agent, but can cause weight gain

(2-4 kg) and hypoglycemia

• Insulin analogues with longer, non-peaking profiles

may decrease the risk of hypoglycemia compared

with NPH insulin

• Premixed insulin is recommended during those with

fixed life style or those who are less educated or less

motivated .

Key Take-Home Messages, cont’d

• When initiating insulin, start with bedtime intermediate-

acting insulin, or bedtime or morning long-acting insulin

• After 2-3 months, if FBG levels are in target range but HbA1c

≥7%, check BG before lunch, dinner, and bed,and, depending

on the results, add 2nd injection (stop sulfonylureas here)

• After 2-3 months, if pre-meal BG out of range, may

need to add a 3rd injection; if HbA1c is still ≥7% check

2-hr postprandial levels and adjust preprandial

rapid-acting insulin.

Thank you allFor

Sparing your valuable time

&

Patient listening

Regimen # 2

First calculate total

daily dose of insulin

Body weight in kgs / 2

• e.g; an 80 kg person will require roughly about

40 units / day.

Dose calculation……..contd

Split the total calculated dose into 4 (four) equal s/c

injections.

– ¼ of total dose as regular insulin s/c half-hour

( ½ hr ) before the three main meals with 6 hrs

gap in between.

– ¼ total calculated dose as NPH insulin s/c at

11:00 p.m. with no food to follow.

Dose calculation: example

For example in an 80-kg diabetic requiring 40 units per day, start with:

• 08:00 a.m. --- 10 units regular insulin s/c ½ hr before breakfast.

• 02:00 p.m. --- 10 units regular insulin s/c ½ hr before lunch.

• 08:00 p.m. --- 10 units regular insulin s/c ½ hr before dinner.

• 11:00 p.m. --- 10 units NPH/ lantus insulin s/c

Dose adjustment

• For adjustment of dosage, check fasting

blood sugar the next day and adjust the

dose of night time NPH Insulin

accordingly i.e. keep on increasing the

dose of NPH by approximately 2 units

daily until you achieve a normal fasting

blood glucose level of 80-110 mg/dl.

Control BSF by adjusting

the prior the dose of NPH

Dose adjustment…contd.• Once the fasting blood glucose has been

controlled, check 6-Point blood sugar as follows:

– Fasting. – 2 hours after breakfast. – Before lunch (and noon insulin) – 2 hours after lunch. – Before dinner (AND EVENING INSULIN)

– 2 hours after dinner

Control random sugar level by adjusting the prior dose of

regular insulin

Dose adjustment…contd.

• Now control any raised random reading by adjusting the dose of previouslyadministered regular insulin.

• For example: a high post lunch reading will NOT be controlled by increasing the dose of next insulin (as in sliding scale), rather adjustment of the pre-lunch regular insulin on the next day will bring down raised reading to the required levels.

Examples

• For the following profile:

– Blood sugar fasting = 180 mg/dl

– Blood sugar after breakfast = 250 mg/dl.

– Blood sugar pre lunch = 190 mg/dl

– Blood sugar post lunch 270 = mg/dl

– Blood sugar pre dinner = 200 mg/dl

– Blood sugar post dinner 260 = mg/dl

• We need to increase the dose of NPH at night to bring down baseline sugar level (BSF) to around 100 mg/dl after which the profile should automatically adjust as follows:– Blood sugar fasting = 100

mg/dl – Blood sugar 02 hrs after

breakfast = 170 mg/dl – Blood sugar pre-lunch =

110 mg/dl – Blood sugar 2 hrs. after

lunch = 190 mg/dl– Blood sugar pre-dinner =

120 mg/dl – Blood sugar 2 hrs. post

dinner = 180 mg/dl

Examples……contd.• Blood sugar fasting = 130 mg/dl • Blood sugar after breakfast = 160 mg/dl• Blood sugar pre-lunch = 130 mg/dl • Blood sugar post lunch = 240 mg/dl• Blood sugar pre-dinner = 180 mg/dl • Blood sugar 2 hrs. post dinner = 200 mg/dl

• This patient needs adjustment of pre-lunch regular Insulin which will bring down post lunch and pre dinner readings within normal limits.

• 2 hrs post dinner blood sugar(200 mg/dl) will be brought down by adjusting pre dinner regular insulin.

Combinations

• In types 2 subjects, once the blood sugar profile is normalized and the patient is not under any stress, the total daily dose (morning + noon + night + NPH at 11 p.m) may be divided into two 12 hourly injections of premixed Insulin

Examples….contd.• e.g-1; If a patient is

stabilized on • 10U R + 12U R +

10U R + 12U NPH;• then he may be

shifted to• 44/2 = 22 units of

70/30 Insulin 12hourly s/c ½ hr before meal.

• e.g-2; If the adjusted Insulin is

• 14U R+16U R+12U R+8U NPH,

• then split the total dose:30 U 70/30 before breakfast and 20U70/30 before dinnerto compensate for the high morning and lunch Insulin.

Combinations………contd.

• Problem: Remember that BD dosing usually fails to cover lunch, especially if it is heavy. So:

• Always check for post lunch hyperglycemia when using this regimen.

• Solution:1. Patients can be advised to take their lunch (heavier

meal) at breakfast; and breakfast (lighter meal) at lunch.

2. Adding Glucobay with lunch some times provides a reasonable control.

3. An alternate combination to overcome the problem is regular insulin for morning and noon, with premixed insulin at night.

Example • 10U R before breakfast + 12U R before lunch + 22U 70/30 before dinner.

• Insulin will be injected exactly 6 hrs apart as in the QID regimen.

Choice of regimens

1. R+ R+ R+ L****

2. R+ R+ R+ N ***

3. R+ R+ premixed insulin**

4. BD premixed insulins*

Regimen # 3

(Pre mixed)

How to start pre mixed (70/30)

Insulin

For pre mixed insulins(70/30 preparations)

Step1:First calculate the total daily starting requirement

of insulin;

body weight(kg)/2

eg, For a 60kg patient,total daily dose =30 units

Step 2:Then devide this dose into 3 equal parts;

10+10+10

Step 3:Give 2 parts in the morning and 1 part in the

evening;

Morning=20U Evening=10 U

Dose titration of Pre-mixed(70/30)

preparations

You can increase or decrease the dose of

pre-mixed insulin by 10 % i.e

If the patients is using,

1-10 units…………….+/- 1 unit

11-20 units……………+/- 2 units

21-30 units……………+/- 3 units

31-40 units……………+/- 4 units…………………..

Advantages and disadvantages

of pre- mixed insulins

Advantages:Easy to administer for the

physician.

Easy to fill and inject by the

patient.

Provides both basal and bolus

coverage with fewer number of

injections.

Disadvantage:

No dose flexability

If u increase/decrease the dose of one

component ,the dose of other

component is also changed un desirably

How to solve the problem of

dosage flexibility

Regimen # 4

Disadvantage of split- mixed regimen

Mid-night hypoglycemia

How to solve the problem of

nocturnal hypoglycemia

Somogyi phenomenon• Due to

– excess dose of night time insulin, or– Night insulin taken early

• Peaks at 3:00 a.m: hypoglycemia• Counter regulatory hormones released in excess:• Resulting in over correction of hypoglycemia:• Fasting hyperglycemia

• Solution:– Check BSL AT 3 :00 a.m– Give long acting at 11:00 p.m so peak comes

later– Reduce dose of night time insulin

Dawn phenomenon• Growth hormone surge at dawn raises insulin

requirement. • Night time insulin taken early, fades out before

dawn. • Fasting hyperglycemia

Solution• Give long acting insulin not before 11 :00 p.m

• May need to increase dose of night time insulin

More physiologic regimens

Remember • Insulin

– No miracle drug

– Has definite indications

As delivery route follows reversephysiology:

– Good control is achieved only if residual pancreatic function is preserved to a certain extent i-e:

–Starting insulin on time is vital(Concept of early insulinization)

Pearls for practice

Never try to control diabetes with oral hypoglycemic drugs / insulin without first ensuring strict diet control.

Always bring fasting sugar to normal before trying to control post prandial / random blood sugar.

Control any underlying infection/stressful condition vigorously.

Keep meal timings regular with 6 hrs between the three meals.

Do not inject NPH before 11 p.m. Keep number of calories during the meals same from day to

day. The quantity and quality of diet should be same at same timings.

Do not use sliding scale to calculate the dose of insulin. Use proper technique to inject s/c insulin. Ensure proper storage of insulin.

Common Problems

Problems can be avoided• Adherence to time table is all that is

required to avoid problems:– Regular meals

– Regular injections

– Regular excercise

Choosing an Insulin with a

Lower Risk of Hypoglycemia

• Insulin analogues with longer, non-peaking

profiles may decrease the risk of

hypoglycemia…

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Injection Techniques

Sites of injection• Arms

• Legs

• Buttocks

• Abdomen

Sites of injection…….contd.• Preferred site of injection is the

abdominal wall due to

• Easy access – Ample subcutaneous tissue

• Absorption is not affected by exercise.

Injection technique

Technique • Tight skin fold

• Spirit…. X

• Appropriate needle size

• 90 degree angle

• Change site to avoid lipodystrophy

Injection technique…….contd.

INSTRUCTIONS:Keep the needle perpendicular to skin in order to avoid variability in absorption (fig-A) Insert needle upto the hilt (fig-A)Distribute daily injections over a wide area to avoid lipodystrophy and other local complications (fig-B)

Storage

• Injections: refrigerate

• Pens: do not refrigerate

Shelf life• One month

once opened

Thank you allFor

Sparing your valuable time

&

Patient listening