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
===========================================
Analogs
Glargine (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
acting
1-2 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 agent
2 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

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…

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
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.

If HbA1c ≤7%...
If HbA1c 7%...
Hypoglycemia
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c 7%...
Step Two…

Step Two: Intensifying Insulin
If 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

Making Adjustments
• Can usually begin with ~4 units and
adjust by 2 units every 3 days until blood
glucose is in range
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…

If HbA1c ≤7%...
If HbA1c 7%...
Hypoglycemia
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

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 premixed 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 all
For
Sparing your valuable time
&
Patient listening

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 previously
administered 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 12
hourly 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 20U
70/30 before dinner
to 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*

How to solve the problem of
dosage flexibility

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

Remember
• Insulin
– No miracle drug
– Has definite indications
As delivery route follows reverse
physiology:
– 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)

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…

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.

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

Ueda2016 wark shop - insulin therapy - mohamed mashahit

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