Berbagai macam insulin

dan cara kerjanya

THE WORLDWIDE PANDEMIC OF

TYPE 2 DIABETES
Indonesia 2030: 21.3 Mil

World wide diabetes

prevalence (millions)

350

300

300

Indonesia: 8.4 Mil

250

221

200
150

150

100
2000

Diabetes care.2004;27:1047-1053

2010

2025

International Diabetes Federation Diabetes Atlas 2000;

Amos et al. Diabet Med 1997;14 (Suppl 5):S1-S85.

Patho-mechanism of type-2 DM
Genetics

Insulin resistance

Environment
Excess energy
intake
Sedentary lifestyle

Obesity
FFA
Glucose
Impaired glucose tolerance

-cell failure

-cell failure
Type 2 diabetes

Liver

Muscle

Adipose

FFA release

Circulation
FFA
Glucose
Pancreas

FFA absorption

Glucose
absorption
Fat

MAJOR METABOLIC
DEFECT IN TYPE-2 DM

Carbohydrates

Intestines

Pharmacologic treatment
of DM

OAD

Liver

Muscle

Adipose
TZD

Biguanide
FFA release

Circulation
Glucose
FFA
Pancreas

Glucose
absorption
AGI

Biguanide

TZD

FFA absorption
Intestinal lipase inhibitor

Fat

Insulin secretagogues

Carbohydrates
Blocks
Promotes

Intestines

INSULIN

Liver

Muscle

Adipose

FFA release

Circulation
Glucose
FFA
Pancreas

Glucose
absorption
AGI

FFA absorption
Intestinal lipase inhibitor

Fat

Carbohydrates

INSULIN

Intestines

The action of human insulin

(onset, peak, and usual effective duration of action)
Glargine/
Detemir

Ultralente

Lente

NPH

Regular

Lispro

Aspart
2

Onset

Peak

10

12

14

Duration

16

18

20

22

24

PROFIL INSULIN SUBKUTAN

Aspart
(very fast)

7 am

Regular
(fast)

12 pm

NPH/Lente
(slow)

7 pm

Insulin
Detemir
(slow)

12 am

Ultralente
(very slow)

7 am

INSULIN

14

The problems related to immunogenicity have been relatively rare since

the use of highly (monocomponent) insulins

ANTI-INFLAMMATORY EFFECTS OF
INSULIN
Decrease CRP
Cell culture: reduce oxidative stress and its associated
apoptosis in cardiomyocytes
Induced endothelial-derived nitric oxide
Human aorta cell and human mononuclear cell culture:
dose-dependent reductions in ROS, proinflammatory
transcription factor NF-kB, ICAM-1, chemokine
monocyte chemoattractant protein (MCP-1)
Inhibit TNF-a and proinflammatory transcription factor
early growth response gene
Clement et al. Diabetes Care 27: 553-591, 2004

Cultural problems

Patients problems
Tool and delivery
problem
Physician problem

 If

you use insulin every day by

injection, that means you are
unhealthy

 Insulin dependency
Pain during injection

Using insulin is the end of your

life

 Lack of knowledge
Willing of using insulin
Hypoglycemic effect of insulin

 Subcutaneous insulin injection drain

into the peripheral, not portal

circulation
Insulin preparation are a poor match
for the finely tuned cell
Subcutaneous insulin absorption is
highly variable (intra-individual and
inter-individual)

50
Non-diabetic insulin
response to mixed meal
40
Plasma insulin (mU/L)

Comparison of change
in the plasma insulin
concentration in
response to a mixed
meal in non-diabetic
subjects, with changes
in free insulin
concentration after a
typical subcutaneous
(SC) dose of shortacting insulin in a type
1 diabetic patient

30

SC short-acting
insulin in
type 1 diabetes

20

10

0
0

1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0

Time (min)

Biotechnology of Insulin Therapy. Oxford: Blackwell Scientific Publications, 1991;1-23

Human Insulin Time-action Pattern

Change in serum insulin

Period of unwanted
hyperglycemia

Normal insulin secretion

at mealtime
Human insulin
Period of unwanted
hypoglycemia

Baseline
level

Time (h)

SC injection

Nonphysiologic Insulin (RI) Replacement

Does Not Mimic -cell Insulin Secretion

Twice daily, intermediate-acting NPH are commonly used as basal insulin

DeWitt DE and Hirsh IB, 2003

Twice as Rapid onset & as High peak

Doubleblind, cross-over, single dose study in healthy volunteers, N=24

(mU/l)

(pmol/l)

500

48 min/ 414 pmol/l

Serum insulin

75

Human Actrapid
(0.2 U/kg)

400

50

NovoRapid

123 min/ 239 pmol/l

300
200

25
100

0
-60

60

120 180 240 300 360 420 480 540 600

Time (minutes)

Heinemann L et al. Diabetes Med 1996;13:683-84

Slide No. 25

 Education

Physician
Patient/family
Population
Modify insulin and its delivery

VALUATIONS OF THERAPEUTIC GOALS

By professionals

Quality of Life

By patients

Quality of Life

Perspective in Life

(Secondary and tertiary prevention)

Expectation of Life

1
Dreyer,1997

INSULIN ANALOGS
Modified structure of the human insulin
resulting altered physicochemical,
biological, and pharmacological
properties

Properties of ideal insulin analogues

Rapid-acting insulin analogues
Onset of action < 0.5 after SC injection
High peak activity
Duration of action < 4 h

Long-acting insulin analogues

Onset of action > 4 h after SC injection
Duration of action 24 h (one injection per day)
No pronounced peak activity
Almost constant action over time
General
Small intra-individual variability of insulin action
Metabolic effect greater than mitogenic effects
No significant immunogenic effects
Chemically stable
No problem with miscibility

The use of insulin analogues

may decrease the risk of
hypoglycemia

 Syringe
Pen insulin ( painless,

easier, more accurate, less

complication)
Insulin pump

Subcutaneous
Intravenous
Intramuscular
Intraperitoneal
Intranasal
Oral

Treatment Modalities
Combination of basal (bed-time) insulin
with oral hypoglycemic agents
Basal plus
- Basal + 1
- Basal + 2
- Basal + 3 (Basal bolus)
Sliding scale

How to use insulin?

Prediabetes
Overt Diabetes

Normal

Metformin
INSULIN

Glucose
mg/dL

SU

Post-prandial
Fasting glucose

350
300
250
200
150
100

Relative to normal
(%)

Insulin resistance

250
200
150
100
50
0

Insulin level
-10

-5

10

Years

15

20

25

30

Algorhytm of Type 2 Diabetes Treatment

Lifestyle (dietary and activity)

Add 1st OHA
(SU or Metformin)
Titrate dose

years

Add 2nd OHA

(Combo)
Titrate dose

COMBO
(SU + Metformin)
Titrate dose

Begin Insulin

months

Add 3rd OHA

(Combo)
Begin Insulin
(Continue 1 OHA)
Titrate dose

Begin Insulin
(Continue 1 OHA)
Titrate dose

1 OHA
Titrate dose

Natural History of Type 2 Diabetes

Insulin sensitivity

Insulin secretion

30%

Type 2 diabetes

50%

50%

IGT

70-100%

70%

100%

Impaired glucose metabolism

Normal glucose metabolism

150%

100%

Diabetes Obes Metab 1999; 1(1): S1

Glucose profiles
Fasting
2 hr post prandial

GLUCOSE
Fasting glucose Normal
2-hr post prandial increase
Fasting glucose increase
2-hr post prandial normal
Fasting glucose increase
2-hr post prandial increase

Glinide,SU,
Metformin,Glitazone,

Prandial insulin

Metformin,
Glitazone, Fasting

insulin

Metformin,
Glitazone,Glinide,SU,

Fasting and
prandial insulin

Less injection
Able to control fasting and prandial
blood glucose
Decrease the amount of insulin needed
More simple than multiple daily
injection
Increase adherence to insulin
Less hypoglycemic episodes?

Targeting the dual glucose profile in diabetic

Detemir+ glinide
Detemir + SU
Detemir + Metformin

Detemir + TZD
Detemir + AGI
Detemir + Incr

* Not yet recommended

Fasting
glucose

Prandial
glucose

Can be given once, twice or three time

daily
Able to control fasting and prandial
glucose
Can be combined with OAD ( some times
glinide or AGI to control prandial glucose
in lunch time if given twice daily)
More adherence

Less hypoglycemia
Better controlled A1C than non analog
insulin
Less weight gain
Flexible delivery
Rapid insulin can be delivered
intravenously

Kendali HbA1c NovoMix lebih baik vs Mixtard

Tingkat keamanan :
Risiko kejadian nokturnal
dan hipoglikemia major
NovoMix30 lebih rendah
dibanding human premix

NovoMix vs.
Humalog Mix 25 and Mixtard 30
p < 0.001
Blood glucose excursion0 5h
(mmol/l h)

21
20
19

p < 0.05

17%

10%

18
17
16

15
14

13
0

Humalog Mix25

NovoMix 30

Mixtard 30

Hermansen K et al. Diabetes Care 2002;25:883888

TAKE HOME MASSAGE

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I : Indikasi
P : Perlu atau Tidak
T : Tehnik (cara pemberian,dosis)
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