Transcript Insulin Therapy

First step into insulin
therapy
(How to start insulin in a patient not controlled on OADs)
By
Dr.Muhammad Tahir Chaudhry
B.Sc.M.B;B.S(Pb).C.diabetology(USA)
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.
Basal insulins
NPH
• Humulin N (Eli Lilly)
• Insulatard (Novo)
(also available as insulatard Novolet pen)
• Dongsulin N (Highnoon)
• Insuget N (Getz)
===========================================
Analogs
Glargine (Lantus)
Lantus Solostar Pen (Sanofi Aventis)
Detemir (Levimir) by Novo
Basal Insulins
Insulin
Type
NPH
Intermediate
acting
1-2 hours
5-7 hours
13-18
hours
Glargine
Long
acting
1-2 hours
Relatively
flat
Upto 24
hours
Long
acting
2-4 hours 8-12 hours
(Lantus)
Aventis
Detemir
(Levimir)Novo
Onset of Peak of Duration
action
action of action
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)
(Also available as Actrapid novolet pen)
• Dongsulin R (Highnoon)
• Insuget R (Getz)
==========================================
Analogs
•
•
•
•
Lispro (Humolog) by Eli Lilly
Novorapid by Novo
Aspart
Glulisine (Apidra) by Sanofi Aventis
Bolous insulins
(Mealtime or prandial)
Insulin
Human
regular
Type
Onset of
action
Short acting 30-60 minutes
Insulin
Rapid acting
analogs
(Lispro,Aspart,
Glulisine)
5-15 minutes
Peak of
action
Duration of
action
2-4 hours
8-10 hours
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)
(Also available as Mixtard 30 Novolet Pen)
• Dongsulin 70/30 (Highnoon)
• Insuget 70/30 (Getz)
===================================
Analogs
• Novomix 30 (Novo)
• Humolog Mix 25(Lilly)
• Humolog Mix 50(Lilly)
Types of Insulin
1. Rapid-acting (Analogs)
2. Short-acting (Regular)
3. Intermediate-acting
4. Premixed
(NPH)
(70/30)
5. Long-acting
6. Extended long-acting
(Lantus)
Indications for Insulin Use in Type 2 Diabetes
Pregnancy (preferably prior to pregnancy)
Acute illness requiring hospitalization
Perioperative/intensive care unit setting
Postmyocardial infarction
High-dose glucocorticoid therapy
Inability to tolerate or contraindication to oral antiglycemic agents
Newly diagnosed type 2 diabetes with significantly elevated blood
glucose levels (pts with severe symptoms or DKA)
Patient no longer achieving therapeutic goals on combination
antiglycemic therapy
Proposed Algorithm of therapy for Type 2
Diabetes
Inadequate
Non pharmacological
therapy
•Severe symptoms
•Severe
hyperglycaemia
1oral agent
2 oral
agents
3 oral
agents
•Ketosis
•pregnancy
Add Insulin Earlier in the Algorithm
First step into
Insulin therapy
What we have in our
pockets?
• Basal Insulins (NPH,Lantus)
• Bolus Insulins(Human Regular)
• Premixed (Human 70/30)
The ADA
Recommendations
on the Use of
Insulin
in Type 2 Diabetes
Touch Pad Question
Currently, roughly ____ of my patients with type
2 diabetes are taking some form of insulin.
1. >80%
2. 60-80%
3. 40-60%
4. 20-40%
5. 0-20%
Touch Pad Question
When it comes to first-line insulin, I tend to
prescribe:
1. An intermediate-acting insulin with
fast-acting insulin as needed
2. A long-acting or extended long-acting
insulin with fast-acting insulin as needed
3.A premixed insulin
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…
Glycemic
control
Hypoglycemia
Rates of Hypoglycemia for Premixed
vs. Long-Acting Insulin + OAD
Mean number of confirmed hypoglycemic events
per patient-year in a 28-week study
Events per patient-year
6
5
p=0.0009
5.73
Premixed insulin
4
Insulin glargine + OADs
3
2
2.62
p=0.0449
1
1.04
p=0.0702
0.05
0.00
0.51
0
Symptomatic
Nocturnal
Severe
Adapted from Janka et al. Diabetes Care 2005;28:254-9.
Rate of event per patient-year
Rates of Hypoglycemia for Premixed
vs. Long-Acting Insulin + OAD in Elderly Patients
12
10
Premixed (n=63)
Glargine + OAD (n=69)
p=0.01
8
p=0.008
6
p=0.06
4
2
0
All episodes of
hypoglycemia
All confirmed
episodes of
hypoglycemia
Confirmed
symptomatic
hypoglycemia
Adapted from Janka HU et al. J Am Geriatr Soc 2007;55(2):182-8.
The ADA Treatment
Algorithm for the Initiation
and Adjustment of Insulin
Initiating and Adjusting Insulin
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
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%...
Continue regimen; check
HbA1c every 3 months
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c 7%...
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)
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
If HbA1c ≤7%...
Continue regimen; check
HbA1c every 3 months
Target range:
Pre-bed BG out of range: add
rapid-acting insulin at dinner
If HbA1c 7%...
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
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
Step One…
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
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%...
Continue regimen; check
HbA1c every 3 months
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c 7%...
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)
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
If HbA1c ≤7%...
Continue regimen; check
HbA1c every 3 months
Target range:
Pre-bed BG out of range: add
rapid-acting insulin at dinner
If HbA1c 7%...
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
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
Step One: Initiating Insulin
• Start with either…
– Bedtime intermediate-acting insulin or
– Bedtime or morning long-acting insulin
Insulin regimens should be designed taking
lifestyle and meal schedules into account
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Step One: Initiating Insulin, cont’d
• Check fasting glucose and increase dose until
in target range
– Target range: 3.89-7.22 mmol/l (70-130 mg/dl)
– Typical dose increase is 2 units every 3 days, but if
fasting glucose >10 mmol/l (>180 mg/dl), can
increase by large increments (e.g., 4 units every 3
days)
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Step One: Initiating Insulin, cont’d
• If hypoglycemia occurs or if fasting glucose
< 3.89 mmol/l (70 mg/dl)…
– Reduce bedtime dose by ≥4 units or 10%
if dose >60 units
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Reduction in overnight and fasting glucose levels achieved
by adding basal insulin may be sufficient to reduce
postprandial elevations in glucose during the day and
facilitate the achievement of target A1C concentrations.
While using basal insulin alone,never stop or reduce ongoing oral
therapy
After 2-3 Months…
• If HbA1c is <7%...
– Continue regimen and check HbA1c every 3
months
• If HbA1c is ≥7%...
– Move to Step Two…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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%.[36] In the remaining patients
with A1C levels above goal regardless of
adequate fasting glucose levels, postprandial
blood glucose levels are likely elevated.
Step Two…
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
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%...
Continue regimen; check
HbA1c every 3 months
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c 7%...
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)
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
If HbA1c ≤7%...
Continue regimen; check
HbA1c every 3 months
Target range:
Pre-bed BG out of range: add
rapid-acting insulin at dinner
If HbA1c 7%...
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
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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
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
When number of insulin Injections increase from
1-2………..Stop or taper of insulin secretagogues
(sulfonylureas).
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
After 2-3 Months…
• If HbA1c is <7%...
– Continue regimen and check HbA1c every
3 months
• If HbA1c is ≥7%...
– Move to Step Three…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Step Three…
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
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%...
Continue regimen; check
HbA1c every 3 months
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c 7%...
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)
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
If HbA1c ≤7%...
Continue regimen; check
HbA1c every 3 months
Target range:
Pre-bed BG out of range: add
rapid-acting insulin at dinner
If HbA1c 7%...
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
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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.
Premixed Insulin
• Not recommended during dose adjustment
• Can be used before breakfast and/or dinner if the
proportion of rapid- and intermediate-acting
insulin is similar to the fixed proportions
available
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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 not recommended during dose
adjustment
Key Take-Home Messages, cont’d
• When initiating insulin, start with bedtime intermediateacting 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.
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 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
Blood
Blood
Blood
Blood
Blood
sugar fasting = 130 mg/dl
sugar after breakfast = 160 mg/dl
sugar pre-lunch = 130 mg/dl
sugar post lunch = 240 mg/dl
sugar pre-dinner = 180 mg/dl
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.
•
•
•
1.
2.
3.
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:
Patients can be advised to take their lunch (heavier
meal) at breakfast; and breakfast (lighter meal) at
lunch.
Adding Glucobay with lunch some times provides a
reasonable control.
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.
2.
3.
4.
R+ R+ R+ L****
R+ R+ R+ N ***
R+ R+ premixed insulin**
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 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)
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 all
For
Sparing your valuable time
&
Patient listening