Insulin

Natural History of Type 2 DM

Normal islet cell

Deposition of amyloid
in T2DM
Insulin
Insulin
Insulin actions
actions include
include ::
Ability
Ability of
of insulin
insulin to
to lower
lower circulating
circulating glucose
glucose
concentrations
concentrations
Suppress
Suppress glucose
glucose production
production :: liver
liver
Stimulate
Stimulate glucose
glucose utilization
utilization :: muscle
muscle plus
plus fat
fat

Additional
Additional metabolic,
metabolic, vascular
vascular &
& mitogenic
mitogenic actions
actions
Frederick Banting

and

Charles Best
(Toronto, 1921)

Marjorie
 Insulin History
1869
Found Islets of Langerhans

1921 1983
Years of animals insulin

1983 1996
Years of highly synthetic purified Human Insulin
( Mixtard, Actrapid, Insulatard )

1996
Years of Insulin Analogues

Future ?
Inhaled, Oral Insulin
 Sejarah Perkembangan
insulin

1921 : penemuan insulin

s/d 1983 : era insulin hewan
Menggunakan ekstrak pankreas hewan (sapi / babi)
1983 : era Human insulin
Menggunakan rDNA manusia untuk menghasilkan insulin
1999 : era insulin modern (analog) dimulai
Menggunakan teknologi bioengineering untuk memodifikasi
rantai DNA human insulin untuk membuat insulin baru yang
lebih baik dalam hal farmakologi
Saccharomyces cerevisiae
 Disadvantage of Human Insulin
Period of unwanted
hyperglycemia
Normal insulin secretion
at mealtime
Change in serum insulin

Human insulin

Period of unwanted
hypoglycemia

Baseline
level

Time (h)
SC injection
 Structural Design Human InsulinNovoRapid (Insulin A
mir (Insulin Detemir)
C1 Asp
4
cha fatt
ya
(My in cid
ri s Phe Gly
tic Phe Arg
ac Glu
id) Tyr
Thr Gly
Pro
Pro Cys
Lys
Thr Val
B29 A21 Asn Cys
Tyr Leu
Gly Lys
A1 Asn Tyr
Ile Glu Leu
Val Leu Ala
Glu
Gln Glu
Gln
Tyr Val
Cys Leu Leu
Cys Thr Ser Ile Cys Ser
His
Ser
Gly
Cys
Leu
B1 Phe Val Asn Gln His
Structural Design Human Insulin
Insulin Lispro (Humalog)

Insulin glargine (Lantus )

Phe Gly Arg
Phe
Tyr Glu
Thr Gly
Pro
Pro Cys
Arg Lys
Arg Thr Val
B29 A21 Asn Cys
Tyr Leu
A1 Gly Asn Tyr
Ile Glu Leu
Gly
Val Leu Ala
Glu
Gln Glu
Gln
Tyr Val
Cys Leu Leu
Cys Thr Ser Ile Cys Ser
His
Ser
Gly
Cys
Leu
B1 Phe Val Asn Gln His
Change in serum insulin A More Physiologic Insulin

Normal insulin
secretion at mealtime

Novorapid

Baseline
Level

Time (h)
SC injection
Profil Insulin Analog sangat mirip dengan Insulin Endogen

---- Insulin endogen

Levemir

---- NovoRapid

NovoMix

Makan Makan Makan Sebelum tidur

Pagi Siang Malam
 New treatment paradigms for
type 2 diabetes
Stepwise treatment

Diet/ Oral Oral Oral

Insulin
exercise monotherapy combination +/- insulin

Early aggressive
combination therapy
 Proactive management of glycaemia:
early combination approach
Diet
and exercise
OAD
monotherapy
10
OAD
combinations OADs
uptitration
HbA1c (%)

9 OAD
+ basal insulin OAD + multiple daily
insulin injections
8

HbA1c = 7%
7

HbA1c = 6.5%
6
Duration of diabetes

*OAD = oral anti-diabetic Del Prato S et al. Int J Clin Pract 2000; 7: 62531.
 TIPE INSULIN
Tipe Insulin Onset Peak/Puncak Duration Duration
(Jam) (Jam) Efektif Maksimal
Rapid Acting
Human Lyspro 0,25-0,5 0,5 2,5 <5 45
Human Aspart <0,20 13 35
Short Acting
Human Regular 0,5 1,0 23 46 57

Intermediate Acting
Human NPH 24 4 10 10 16 14 18
Human Lente 34 4 12 12 18 16 20
Long Acting
Human Ultralente 6 10 14 24 18 20 20 - 36
Insulin Glargine 2-4 Peakless 20 -24
Combinations
Mixtard
Novomix
Indications of Insulin Treatment
Indication for the use of insulin in
Type 2 DM
In
In severe
severe metabolic
metabolic decompensation
decompensation
Ketoacidosis
Ketoacidosis
Hyperosmolar
Hyperosmolar non non ketotic
ketotic coma
coma
Lactic
Lactic acidosis
acidosis
Severe
Severe stress
stress ::
Systemic
Systemic infection
infection
Major
Major surgery
surgery
Weight
Weight loss
loss within
within aa short
short period
period of
of time
time
Pregnancy
Pregnancy ifif diet
diet does
does not
not succeed
succeed toto control
control
glycemia
glycemia
OHA
OHA failure
failure or
or contra-indication
contra-indication ofof OHA
OHA
Combination Therapy in T2DM:
Insulin Plus Oral Hypoglycemic Agents
Insulin Plus Sulphonylurea - BIDS
Some insulin is endogenous, with natural
secretory pattern
Biguanide Plus Insulin
Reduces hepatic insulin resistance
May achieve better control with less insulin
Can reduce weight gain
Alpha Glucosidase Inhibitor Plus Insulin
Reduces posotprandial glucose level
Thiazolidinedione Plus Insulin
Reduces peripheral insulin resistance
Reduces insulin requirement
Must balance TZD and insulin carefully to minimize
weight gain
Benefits
Benefits of
of Insulin
Insulin and
and Oral
Oral Agents
Agents Combination
Combination

Improves
Improves glycemic
glycemic control
control
Treats
Treats multiple
multiple physiologic
physiologic abnormalities
abnormalities
Less
Less insulin
insulin is
is needed
needed to
to achieve
achieve good
good glycemic
glycemic
control
control
Reduces
Reduces potensial
potensial for
for weight
weight gain
gain
Patients:
Patients:
more
more practical
practical and
and less
less frightening
frightening
improved
improved psychological
psychological acceptance,
acceptance, patients
patients
continue
continue the
the oral
oral drugs
drugs
less
less // minimal
minimal education
education is is needed
needed
treatment
treatment can
can bebe started
started inin an
an
outpatients-setting
outpatients-setting
better
better compliance,
compliance, and
and cost
cost may
may be
be less
less
 Glycemic Control: Recommended goals

Measurement Normal IDF1 ADA/EASD2 AACE3 PERKENI

A1c* <6% <6.5% <7% <6.5% <6.5%

Fasting Gluc <100 <110 90-130 <110 80-110

PP (2h) Gluc <140 <155 <180 <140 80-145

* Realistic Target: Lowest A1c possible without unacceptable adverse effects

IDF = International Diabetes Federation

ADA = American Diabetes Association.
AACE = American Association of Clinical Endocrinology
1. Global guideline for type 2 diabetes clinical guidelines taskforce (Brussels: IDF,2005)
2. Nathan DM et al. Diabetologia 2006;49:1711-21.
3. http://www.aace.com/pub/odimplementation/roadmap.pdf
 When to Start
Insulin Therapy ?
 Insulin can be initiated anytime
Traditionally, insulin had been reserved as the last line of therapy
Considering the benefits of normal glycemic status,
insulin can be initiated earlier, as soon as is required.

+
+
3 OAD
Inadequate +
Lifestyle 1 OAD
2 OAD

Initiate Insulin
Indication: Permanent Not permanent
T1DM Infection
OAD failure Pregnancy
OAD Contra Indication Hospitalized
Diabetic Ketoacidosis Perioperative
 How to Start
Insulin Therapy ?
1. If Fasting BG is elevated, start for basal insulin
with long acting insulin (Levemir)

2. If Prandial BG is elevated, start for prandial

/bolus insulin with rapid acting insulin
(NovoRapid)
3. If Fasting and Post Prandial are elevated :
- Oral agent with basal insulin
- premix insulin (NovoMix)
- basal/bolus as in multiple daily injection (MDI)
 Treatment Based on Type of Hyperglycemia

BASAL PRANDIAL CONCEPT

Fasting Hyperglycemia Prandial

Treat fasting hyperglyc. first

Continue oral agent
SMBG is important

Basal Insulin (Levemir) Prandial Insulin (NovoRapid)

 The Novo Syringe
1925 First home use syringe
 Insulin Injection Development
1989 1920s 1925
1960

From syringes to safe

and convenient portable
1985pens with insulin
cartridges

More insulin pen introductions in the 1990s

Suntikan pada
Daerah gluteus
Lokasi penyuntikan :
1. Lengan atas bagian luar
2. Paha atas bagian depan
3. Abdomen (kec. 2 inci dari pusat)
4. Daerah pantat ( gluteus )
Cara mengkocok
Insulin sebelum
injeksi
Teknik Injeksi Insulin pada
Lengan atas bagian luar
Contoh cara penyuntikan pada abdomen
 NovoFine 6 mm
safe and effective deposition
2.5 mm

6 mm
needle

8 mm

12 mm
needle
Kendala dalam terapi Insulin

I dont want it.!

It hurts ! Expensive !

Drug
addiction ?